Novel methods and uses

Abstract

The present invention relates inter alia to methods for identifying a substance useful for the prevention or treatment of a disease, disorder, or condition associated with altered NLRX1 activity, and uses of said substances in the prevention or treatment of a disease, disorder, or condition associated with altered NLRX1 activity, for example in the prevention or treatment of Parkinson's disease or amyotrophic lateral sclerosis.

Description

[0001]Novel Methods and Uses FieldThe invention relates inter alia to methods for identifying a substance useful for the preventionor treatment of a disease, disorder, or condition associated with altered NLRX1 activity, anduses of said substances. Background of the Invention The mitochondria permeability transition pore (mPTP) is a high conductance channel residing on the inner mitochondrial membrane that is activated under certain conditions of cellular stress, in particular excessive Ca2+loading and oxidative stress. Due to the role of the mPTP in regulating oxidative phosphorylation and in mitochondria-related apoptosis or necrosis, it has been implicated in a number of degenerative and metabolic diseases. Indeed, although the precise molecular identity of the mPTP is not known, genetic or pharmacological inhibition of the peptidyl prolyl cis-trans isomerase F (Ppif; Uniprot ID P30405; also known as cyclophilin D), which is accepted as a key regulator of the pore, significantly decreases the sensitivity of pore opening in response to Ca2+loading and other mPTP activators. Consequently, genetic ablation or pharmacological inhibition of Ppif hasbeen utilised to evaluate involvement of the mPTP in pathological pathways in cell and animaldisease models. In particular, genetic knockout of Ppif was shown to be protective in variouspreclinical in vivo transgenic models of neurodegenerative disease including Alzheimer’sdisease, Parkinson’s disease and motor neuron disease, also known as Amyotrophic Lateral Sclerosis (ALS), demonstrating the therapeutic potential of mPTP inhibition. Accordingly, there has been significant interest in identifying new substances which are inhibitors of the mPTP, and which consequently may have utility in the prevention or treatmentof diseases related to the mPTP, such as degenerative and metabolic diseases. Indeed, thepresent inventors have previously identified novel compounds which inhibit mPTP activity. For example, see WO2022 / 049376, WO2022 / 049377, and WO2023 / 166303.However, due to the unknown molecular identity of the mPTP, and the complex interactionsbetween the mPTP and other agents which modulate mPTP activity, the precise mechanism by which inhibition of the mPTP was achieved by the aforementioned novel compounds has not been elucidated. It is desirable to clarify the mechanism by which mPTP inhibition is achieved as it may allow the efficiency of the compound screening, hit and lead identification, and lead optimisation processes to be improved.The present inventors have discovered that the novel compounds developed previously, whichinhibit the activity of the mPTP, bind to nucleotide-binding oligomerization domain, leucine richrepeat containing X1 protein (NLRX1; see Background Examples 1 and 2). Accordingly,inhibition of the activity of the mPTP by the novel compounds developed previously ismediated via binding to NLRX1.NLRX1 is a member of the NOD-like receptor (NLR) family of cytoplasmic pattern recognitionreceptors (PRRs), and so is understood to have an important role in innate immunity (Liu etal.2022). However, NLRX1 is at present the only NLR known to be located in mitochondria which therefore allows it to co-ordinate the link between mitochondrial function and innateimmunity (Chu et al. 2019). Indeed, NLRX1 has been shown to have an important role inmaintaining mitochondrial homeostasis and metabolic balance, as well as apoptosis and autophagy. NLRX1 is a known regulator of inflammation, although its precise role is somewhat unclear.For example, NLRX1 has been reported to weaken the innate immune response via (i)reduction in activation of the RIG-I-MAVS pathway in response to viral infection, for examplevia direct binding to the mitochondrial antiviral signal protein (MAVS) (Nagai-Singer et al.2019) or (ii) competition with the retinoic acid-inducible gene I (RIG-I) protein resulting in reduced formation of the immunostimulatory interferon regulatory factor 3 (IRF3) homodimer(Allen et al.2011). Moreover, due to its role in maintaining mitochondrial homeostasis, NLRX1may inhibit the inflammatory response which is activated upon infliction of damage to themitochondria (Chu et al. 2019). However, conversely, NLRX1 has also been reported to bepro-inflammatory in alternative contexts. For example, genetic knock-out of NLRX1 has been shown to dampen pro-apoptotic signalling and limit resultant cell death in mice suffering fromhyperoxic acute lung injury (Kim et al. 2023). Moreover, a deficiency in NLRX1 has beendemonstrated to result in an increase in the number of reparative macrophages, which are able to regulate the immune response and heal damaged tissue, in the context of ischaemicinjury (Li et al. 2023). Finally, NLRX1 has been reported to have a pro-inflammatory role inthe development of diet-induced type 2 diabetes mellitus (Costford et al.2018).In view of the known role of NLRX1 in regulating inflammation, it has been implicated in anumber of diseases. In particular, NLRX1 has been implicated in an experimental autoimmuneencephalomyelitis (EAE) model (Eitas et al. 2014) and, consequently, multiple sclerosis (MS)(Gharagozloo et al. 2019), which is itself an autoimmune disease characterised bymitochondrial dysfunction. Moreover, NLRX1 has been linked to Alzheimer’s disease and Parkinson’s disease since each of these conditions may be caused by a glutamate imbalance,whilst NLRX1 is known to regulate the glutamate cycle (Leber et al.2018).It should be noted that the above neurological degenerative diseases are also associated with the mPTP. Indeed, novel compounds developed previously by the present inventors, which inhibit the mPTP, have been indicated for use in the treatment of inter alia Alzheimer’s disease, Parkinson’s disease, ALS, and multiple sclerosis. The discovery by the present inventors thatsaid mPTP inhibitors actually bind to NLRX1 explains this overlap in disease association.In addition to the above-described central nervous system (CNS) disorders, NLRX1 is associated with a myriad of other diseases and conditions, which are not necessarilyassociated with the mPTP. For example, the role of NLRX1 in immunity, in particular innateimmunity, have led to studies which elucidate the association between NLRX1 andautoimmune diseases such as systemic lupus erythematosus (SLE), inflammatory boweldisease (IBD), rheumatoid arthritis (RA), and atopic dermatitis (AD) (Jang et al. 2020;Triantafilou, 2021). Moreover, NLRX1 has been purported to have a role in cancer, forexample hepatocellular carcinoma, breast cancer, head and neck squamous cell carcinoma,gastric cancer, and histiocytic sarcoma (Castaño-Rodríguez et al. 2015; Wang et al. 2017).NLRX1 has also been implicated in metabolic diseases such as type 2 diabetes mellitus (Zenget al. 2017), non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatohepatitis(NASH) (Kors et al. 2018). In addition, due to its role in innate immunity, NLRX1 may clearlyhave a role in pathogen infection, for example wherein the pathogen is Helicobacter pylori(Castaño-Rodríguez et al. 2015) or influenza (Varga and Palese, 2011).In view of the association of NLRX1 with a diverse range of diseases and disorders, as summarised above, and the discovery made by the present inventors that inhibition of themPTP is mediated via binding to NLRX1, the present inventors have consequently discoveredthat said existing compounds may have utility in the treatment of a range of additional diseasesor disorders associated with altered NLRX1 activity.Furthermore, as noted above, there has been significant interest in identifying new substances which are inhibitors of the mPTP. However, there remains a significant challenge in identifying novel substances which may have mPTP inhibitory activity. Consequently, there remains a need for new and efficient methods for the identification of inhibitors of mPTP activity.The discovery made by the present inventors, that inhibition of mPTP activity is mediated viabinding to NLRX1, to which substances may be screened for binding. That is the presentinventors have discovered that screening existing, or new, substances for NLRX1 binding mayresult in new entities being identified which may be predicted to have mPTP inhibitory activity. The present invention therefore relates to novel methods and assays for screening existing,or new, substances for binding to NLRX1 and for mPTP inhibitory activity.Summary of the InventionThe present invention provides a method for identifying a substance useful for the preventionor treatment of a disease, disorder, or condition associated with altered NLRX1 activity , whichmethod comprises determining whether said substance (i) binds to NLRX1 and (ii) inhibitsactivity of the mPTP and, if it does, identifying said substance as a substance useful for theprevention or treatment of said disease, disorder, or condition associated with altered NLRX1 activity. The present invention also provides a substance which is (i) capable of binding to NLRX1 and (ii) capable of inhibiting activity of the mPTP, for use in the prevention or treatment of adisease, disorder, or condition associated with altered NLRX1 activity .Furthermore, the present provides known inhibitors of mPTP activity, in particular a substanceof formula (I), (II), (III), (IV), (V), (VA), (VI), or (VIB), as described below, for use in theprevention or treatment of a disease, disorder, or condition associated with altered NLRX1 activity, in particular wherein said disease, disorder, or condition is an Other NLRX1-RelatedDisease, Disorder or Condition (as defined herein).Brief Description of the Figures Figures 1 and 2: Show the proteins / peptides identified, and in particular NLRX1, as potentialbinding partners of known inhibitors of the mPTP via affinity-based chemoproteomicsexperiments (see Background Example 1).Figure 3: Shows the effect of genetic deletion of NLRX1 on activity of the mPTP, as detected by fluorescence in a mitochondrial calcium retention assay. Moreover, shows the effect of treatment with cyclosporin A and a known inhibitor of the mPTP on the activity of the mPTP inwild-type and NLRX1 knock-out (KO) cells (see Background Example 2).Figure 4: Shows the effect of a known inhibitor of the mPTP, Test Substance 1, on the Tm(i.e. midpoint value of melting temperature) of NLRX1 in a cellular thermal shift assay (CETSA; see NLRX1 Binding Example 1).Figure 5: Shows the ability of a range of Test Substances to bind and stabilise NLRX1 tovarying degrees in a cellular thermal shift assay (CETSA; see NLRX1 Binding Example 1).Figures 6 and 7: Show the ability of two different Probe Substances to specifically bind toNLRX1-expressing membranes to be used in a filtration binding assay according to the present invention. Moreover, show the lack of any specific binding of said Probe Substancesto membranes which lack NLRX1 (see NLRX1 Binding Example 2).Figures 8 and 9: Show the ability of two different Test Substances to bind to NLRX1,quantified by a reduction in bioluminescence resonance energy transfer (BRET) signal, in a nano-BRET assay (see NLRX1 Binding Example 3).Figure 10: Shows the effect of an mPTP Inhibitor, upon treatment at a dose of 50 mg / kg or150 mg / kg, on the levels of the neurofilament-light (NFL) protein, in both the plasma andcerebrospinal fluid (CSF), in the ΔNLS TDP43 mouse model of amyotrophic lateral sclerosis(ALS) (see Biological Example 1).Figures 11 and 12: Show the effect of an mPTP Inhibitor, upon treatment at a dose of 10mg / kg, 50 mg / kg, or 150 mg / kg, on the levels of the astrocyte activation marker, GFAP, in theplasma in the ΔNLS TDP43 mouse model of amyotrophic lateral sclerosis (ALS) (see Biological Example 1).Figure 13: Shows the effect of an mPTP Inhibitor, upon treatment at a dose of 50 mg / kg, onthe level of the pro-inflammatory cytokine IL-1β, in the brain cortices in the ΔNLS TDP43mouse model of amyotrophic lateral sclerosis (ALS) (see Biological Example 1).Figure 14: Shows the effect of an mPTP Inhibitor, upon treatment at a dose of 50 mg / kg, onthe expression of specific mRNA transcripts in the brain cortices, which are differentially expressed between ΔNLS TDP43 and wild-type mice, as assessed via RNAseq (see Biological Example 1).Figure 15: Shows a table reporting the effect of an mPTP Inhibitor, upon treatment at a doseof 50 mg / kg, on the expression of specific mRNA transcripts in the brain cortices, which are differentially expressed between ΔNLS TDP43 and wild-type mice, as assessed via RNAseq and qPCR analyses (see Biological Example 1).Figure 16: Shows the effect of an mPTP Inhibitor, upon treatment at a dose of 10 mg / kg or50 mg / kg, on the expression of the Isg15 and GFAP mRNA transcripts, which are differentiallyexpressed between ΔNLS TDP43 and wild-type mice (see Biological Example 1).Figure 17: Shows the effect of an mPTP Inhibitor, upon treatment at a dose of 50 mg / kg or150 mg / kg, on the expression of pro-inflammatory cytokine mRNA transcripts, namely TNFα,IL-6, IL-1β, and CCL2, in the brain cortices of rats treated with pilocarpine, and thus induced into a seizure, as assessed via qPCR (see Biological Example 2).Figure 18: Shows the effect of an mPTP Inhibitor, upon treatment at a dose of 10 mg / kg, 50mg / kg or 150 mg / kg, on the levels of the neurofilament-light (NFL) protein, in both the plasmaand cerebrospinal fluid (CSF), in the pilocarpine-induced rat seizure model (see BiologicalExample 2).Figure 19: Shows the ability of a radiolabelled Test Substance to bind to wild-type andNLRX1-knockout out coronal brain sections, without specific binding of said radiolabelled TestSubstance to brain sections which lack NLRX1 (see NLRX1 Binding Example 4).Figure 20: Shows the saturation curve for binding of a radiolabelled Test Substance to wild-type coronal brain sections (see NLRX1 Binding Example 4). Detailed Description of the Invention Conditions to be TreatedIn one aspect, the present invention provides a method for identifying a substance useful forthe prevention or treatment of a disease, disorder, or condition associated with altered NLRX1 activity, which method comprises determining whether said substance (i) binds to NLRX1 and (ii) inhibits activity of the mPTP and, if it does, identifying said substance as a substance useful for the prevention or treatment of said disease, disorder, or condition associated with alteredNLRX1 activity. Suitable methods of the invention are described under the sub-heading‘Methods for Identifying Substances for use according to the present invention’ below.In another aspect of the present invention, there is provided a substance which is (i) capableof binding to NLRX1 and (ii) capable of inhibiting the activity of the mPTP. In particular thereis provided a substance which (i) binds NLRX1 and (ii) inhibits the activity of the mPTP. In aparticular aspect of the present invention, there is provided a substance which is (i) capableof binding to NLRX1 and (ii) capable of inhibiting the activity of the mPTP, which is identified by a method according to the present invention, for example a method described under the sub-heading ‘Methods for Identifying Substances for use according to the present invention’below. That is, there is provided a substance which (i) binds NLRX1 and (ii) inhibits the activityof the mPTP, which is identified by a method according to the present invention, for example a method described under the sub-heading ‘Methods for Identifying Substances for use according to the present invention’ below.Accordingly, in a further aspect of the present invention, there is provided a substance whichis (i) capable of binding to NLRX1 and (ii) capable of inhibiting the activity of the mPTP, foruse in the prevention or treatment of a disease, disorder, or condition associated with altered NLRX1 activity. In particular, there is provided a substance which (i) binds NLRX1 and (ii) inhibits the activity of the mPTP, for use in the prevention or treatment of a disease, disorder,or condition associated with altered NLRX1 activity. In a particular aspect of the presentinvention, there is provided a substance which is (i) capable of binding to NLRX1 and (ii)capable of inhibiting the activity of the mPTP, which is identified by a method according to the present invention, for example a method described under the sub-heading ‘Methods for Identifying Substances for use according to the present invention’ below, for use in the prevention or treatment of a disease, disorder, or condition associated with altered NLRX1activity. That is, there is provided a substance which (i) binds NLRX1 and (ii) inhibits theactivity of the mPTP, which is identified by a method according to the present invention, for example a method described under the sub-heading ‘Methods for Identifying Substances for use according to the present invention’ below, for use in the prevention or treatment of a disease, disorder, or condition associated with altered NLRX1 activity. As used herein, the terms ‘therapeutic effect’, ‘treatment’ or ‘treating’ include the control, mitigation, reduction or modulation of the state of the disease, disorder, or condition, or the symptoms of the disease, disorder, or condition.As used herein, the terms ‘prophylactic effect’, ‘prophylaxis’, ‘prevention’, or ‘preventing’ referto, in addition to preventing the occurrence of a disease, disorder, or condition, preventingsymptoms of a disease, disorder, or condition in a subject, or preventing recurrence ofsymptoms of a disease, disorder, or condition, in an afflicted subject.As used herein, a disease, disorder, or condition associated with altered NLRX1 activity maybe defined as any disease, disorder, or condition in which the activity of NLRX1 is thought or is known to contribute to the establishment, progression, maintenance, or symptoms of the disease, disorder, or condition, for example those diseases, disorders, and conditionsmentioned herein below. Suitably, the disease, disorder, or condition associated with alteredNLRX1 activity is associated with excessive or undesired activity of NLRX1, which may bedefined as any disease, disorder, or condition in which the activity of NLRX1 at a level whichexceeds the activity of NLRX1 within a normal range, or its dysregulation, in particular in ahealthy individual, is thought or is known to contribute to the establishment, progression,maintenance, or symptoms of the disease, disorder, or condition, for example those diseases, disorders, and conditions mentioned herein below. As discussed above, the present inventors have discovered that the mitochondria permeability transition pore (mPTP) is regulated by NLRX1, and that inhibition of mPTP by existingcompounds is mediated via binding to NLRX1. Without being limited by theory, said bindingto NLRX1 is believed to lead to regulatory modulation of NLRX1, for example, activation orinhibition of NLRX1 activity (such as NLRX1 signalling activity), particularly inhibition of NLRX1activity. Therefore, in any of the above-described aspects of the invention, the substance which binds to NLRX1 is suitably capable of inhibiting the activity of NLRX1, i.e. the substance which binds to NLRX1 is an inhibitor of NLRX1. Accordingly, suitably, the present inventionprovides methods for identifying inhibitors of NLRX1 which are useful for the prevention ortreatment of a disease, disorder, or condition associated with altered NLRX1 activity, and further provides inhibitors of NLRX1 activity which have been identified by methods according to the present invention.Therefore, diseases, disorders, or conditions associated with altered NLRX1 activity include(i) diseases, disorders, or conditions associated with activation of the mPTP, and (ii) otherdiseases, disorders, or conditions associated with altered NLRX1 activity , i.e. but which arenot defined herein as diseases, disorders, or conditions associated with activation of the mPTP(herein referred to as “Other NLRX1-Related Diseases, Disorders or Conditions”).As used herein, a disease, disorder, or condition associated with activation of the mitochondriapermeability transition pore (mPTP) may be defined as any disease, disorder, or condition inwhich the activity of the mPTP at a level which exceeds the activity of the mPTP within a normal range, in particular in a healthy individual, is thought or is known to contribute to the establishment, progression, maintenance, or symptoms of the disease, disorder, or condition,for example those diseases, disorders, and conditions mentioned herein below. Suitably, thedisease, disorder, or condition associated with activation of the mPTP is associated withexcessive activity of the mPTP, which may be defined as any disease, disorder, or conditionin which the activity of the mPTP at a level which exceeds the activity of the mPTP within anormal range, in particular in a healthy individual, is thought or is known to contribute to the establishment, progression, maintenance, or symptoms of the disease, disorder, or condition, for example those diseases, disorders, and conditions mentioned herein below. In one aspect of the present invention, the disease, disorder, or condition, which is associatedwith altered NLRX1 activity is an autoimmune, an acute or chronic inflammatory, an allergic,a degenerative such as a neurodegenerative, a mitochondrial, a respiratory or pulmonary, acardiovascular, a central nervous system i.e. neurological, a metabolic, an infectious or pathogenic, a hyperproliferative (e.g. cancer), a renal, a hepatic, or a skin, disease, disorder, or condition. The skilled person would understand that a single disease, disorder, or condition, which isassociated with altered NLRX1 activity, and which is associated with activation of the mPTP,or which is an Other NLRX1-Related Disease, Disorder or Condition, may fall into one of more of the above categories of disease, disorder, or condition. For example, a disease, disorder, or condition, which is associated with altered NLRX1 activity, may simultaneously be an acute or chronic inflammatory disease, disorder, or condition and a respiratory or pulmonary disease, disorder, or condition, e.g. asthma.Suitably, the disease, disorder, or condition, which is associated with activation of the mPTPis a degenerative such as a neurodegenerative, or a central nervous system i.e. neurological, disease, disorder, or condition. In one aspect of the invention, the disease, disorder, or condition, which is associated withactivation of the mPTP is a degenerative disease, disorder, or condition such as aneurodegenerative disease, disorder, or condition. For example, in one aspect, the disease,disorder, or condition, which is associated with activation of the mPTP, is selected fromParkinson’s disease, dementia with Lewy bodies, Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis, frontal temporal dementia, chemotherapy induced neuropathy, Huntington’s disease, epilepsy, Charcot-Marie-Tooth disease, multiple system atrophy, spinocerebellar ataxias, progressive supranuclear palsy, hereditary spastic paraplegia, Duchenne muscular dystrophy, congenital muscular dystrophy, inclusion body myositis, traumatic brain injury and Friedreich’s ataxia. In one aspect, the disease, disorder, orcondition, which is associated with activation of the mPTP is a degenerative disease, disorder,or condition, which is not a degenerative disease, disorder, or condition, of the central nervoussystem i.e. neurological disease, disorder, or condition. For example, the disease, disorder,or condition, which is associated with activation of the mPTP, is selected from hereditaryspastic paraplegia, Duchenne muscular dystrophy, inclusion body myositis, and congenitalmuscular dystrophy.In one aspect, the disease, disorder, or condition, which is associated with activation of themPTP is a central nervous system disease, disorder, or condition i.e. is a neurological disease, disorder, or condition. In particular, in one aspect, the disease, disorder, or condition, which isassociated with activation of the mPTP is a degenerative disease, disorder, or condition, suchas a neurodegenerative disease, disorder, or condition of the central nervous system. For example, in one aspect, the disease, disorder, or condition, which is associated with activation of the mPTP, is selected from Parkinson’s disease, dementia with Lewy bodies, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, frontal temporal dementia, chemotherapy induced neuropathy, Huntington’s disease, epilepsy, Charcot-Marie-Toothdisease, multiple system atrophy, spinocerebellar ataxias, progressive supranuclear palsy,traumatic brain injury and Friedreich’s ataxia. In one particular aspect, the disease, disorder, or condition, which is associated with activationof the mPTP is Parkinson’s disease. In an alternative particular aspect, the disease, disorder,or condition, which is associated with activation of the mPTP is amyotrophic lateral sclerosis.Suitably, the disease, disorder, or condition, which is associated with activation of the mPTPis a mitochondrial disease, disorder, or condition. For example, in one aspect, the disease,disorder, or condition, which is associated with activation of the mPTP, is selected from Reyesyndrome, Leber’s hereditary optic neuropathy and associated disorders and disorders, suchas those diseases and disorders disclosed in CA2884607A1 (Stealth Peptides InternationalInc.), which is herein incorporated by reference in its entirety.Suitably, the disease, disorder, or condition, which is an Other NLRX1-Related Disease,Disorder or Condition, is an autoimmune, an acute or chronic inflammatory, an allergic, arespiratory or pulmonary, a cardiovascular, an infectious or pathogenic, a hyperproliferative (e.g. cancer), a renal, a hepatic, or a skin, disease, disorder, or condition. In one aspect, the disease, disorder, or condition, which is an Other NLRX1-Related Disease,Disorder or Condition is an autoimmune disease, disorder, or condition. In particular, in oneaspect, the disease, disorder, or condition is selected from inflammatory bowel disease (IBD) (e.g., Crohn’s disease and ulcerative colitis), irritable bowel syndrome (IBS), lupus, systemic lupus erythematosus, rheumatoid arthritis, Sjogren’s syndrome, systemic scleroderma, type 1 diabetes mellitus, psoriasis (including psoriatic arthritis), autoimmune encephalitis, sarcoidosis, Guillain-Barre syndrome, Grave’s disease, antiphospholipid syndrome and cancer-immunotherapy-induced autoimmune diseases. In one aspect, the disease, disorder, or condition, which is an Other NLRX1-Related Disease,Disorder or Condition is an acute or chronic inflammatory, or an allergic, disease, disorder, orcondition. In particular, in one aspect, the disease, disorder, or condition is selected from asthma, cirrhosis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), metabolic syndrome, chronic granulomatous disease, graft versus host disease,tumor necrosis factor receptor associated periodic syndrome, hay fever (seasonal allergies),sinusitis, eczema (atopic dermatitis), contact dermatitis, hives (urticaria), and eosinophilic gastrointestinal disorder. In one aspect, the disease, disorder, or condition, which is an Other NLRX1-Related Disease,Disorder or Condition, is a respiratory or pulmonary disease, disorder, or condition. Inparticular, in one aspect, the disease, disorder, or condition is selected from asthma, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, idiopathic pulmonary fibrosis (IPF), and emphysema. In one aspect, the disease, disorder, or condition, which is an Other NLRX1-Related Disease, Disorder or Condition, is a metabolic disease, disorder, or condition. In particular, in one aspect, the disease, disorder, or condition is selected from type 1 diabetes mellitus, type 2 diabetes mellitus, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), metabolic syndrome, diabetic ketoacidosis, obesity, and pre-diabetes. In one aspect, the disease, disorder, or condition, which is an Other NLRX1-Related Disease, Disorder or Condition, is an infectious or pathogenic disease, disorder, or condition. In particular, in one aspect, the disease, disorder, or condition is selected from a bacterial infection, a viral infection and a fungal infection, and any disease, disorder, or condition resulting from said bacterial, viral or fungal infection e.g. pneumonia, tuberculosis, cholera. Non-limiting examples of bacterial infection include infections of Bacillus anthracis, Bacillus cereus, Bordetella pertussis, Borrelia burgdorferi, Brucella abortus, Brucella canis, Brucella melitensis, Brucella suis Campylobacter jejuni Chlamydia pneumoniae, Chlamydia trachomatis, Chlamydophila psittaci, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Corynebacterium diphtheriae, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Francisella tularensis, Haemophilus influenzae, Helicobacter pylori, Legionella pneumophila, Leptospira interrogans, Listeria monocytogenes, Mycobacterium leprae, Mycobacterium tuberculosis, Mycobacterium ulcerans, Mycoplasma pneumoniae, Neisseria gonorrhoeae, Neisseria meningitidis, Pseudomonas aeruginosa, Rickettsia rickettsii, Salmonella typhi, Salmonella typhimurium, Shigella sonnei, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, Yersinia pestis, Yersinia enter ocolitica, Yersinia pseudotuberculosis. Non-limiting examples of viral infection include infections of viruses in the family adenoviridae; viruses in the family herpesviridae, such as herpes simplex type 1 (HSV1), herpes simplex type 2 (HSV2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), human herpesvirus (HHV); viruses in the family papillomaviridae, such as human papillomaviruses; viruses in the family polyomaviridae; viruses in the family poxviridae; viruses in the family hepadnaviridae such as hepatitis B virus (HBV); viruses in the family parvoviridae; viruses in the family astroviridae; viruses in the family caliciviridae; viruses in the family picomaviridae such as coxsackievirus, hepatitis A virus, poliovirus, and rhinovirus; viruses inthe family coronaviridae such as severe acute respiratory syndrome (SARS) viruses; virusesin the family flaviviridae such as hepatitis C virus (HCV), yellow fever virus (YFV), denguevirus (DENV), and West Nile virus, viruses in the family togaviridae such as rubella virus;viruses in the family hepeviridae; viruses in the family retroviridae such as human immunodeficiency virus (HIV); viruses in the family orthomyxoviridae such as influenza virus;viruses in the family arenaviridae; viruses in the family bunyaviridae such as Crimean-Congohaemorrhagic fever virus; viruses in the family filoviridae such as Ebola virus and Marburg virus; viruses in the family paramyxoviridae such as measles virus, mumps virus, parainfluenza virus, respiratory syncytial virus (RSV), human metapneumovirus, Hendra virus, and Nipah virus; viruses in the family rhabdoviridae such as rabies virus; and viruses in the family reoviridae, among others. Non-limiting examples of fungal infections include infection of fungi of the genus Aspergillus, which cause aspergillosis; fungi of the genus Blastomyces, which cause blastomycosis; fungi of the genus Candida, such as Candida albicans, which cause candidiasis; fungi of the genusCoccidioides; fungi of the genus Cryptococcus, such as Cryptococcus neoformans andCryptococcus gattii, which cause cryptococcosis; dermatophytes fungi, which cause ringworm; fungi of the genus Histoplasma, such as Histoplasma capsulatum, which cause histoplasmosis; fungi of the order Mucorales, which cause mucormycosis; fungi of the genus Saccharomyces, such as Saccharomyces cerevisiae; fungi of the genus Pneumocystis, such as Pneumocystis jirovecii, which cause pneumocystis pneumonia; and fungi of the genus Sporothrix which cause sporotrichosis. In one aspect, the disease, disorder, or condition, which is an Other NLRX1-Related Disease,Disorder or Condition is an hyperproliferative disease, disorder, or condition, e.g. cancer. Inparticular, in one aspect, the disease, disorder, or condition is selected from breast cancer, lung cancer, liver cancer e.g. hepatocellular carcinoma, skin cancer e.g. melanoma, familial adenomatous polyposis (PAP), throat cancer, thyroid cancer, cancers of the gastrointestinal tract, cervical cancer, bladder cancer, pancreatic cancer, prostate cancer, renal cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, acute myeloid leukaemia, acute lymphoblastic leukaemia, chronic myeloproliferative disorders, hypereosinophilic syndrome, mastocytosis, among others. In one aspect, the disease, disorder, or condition, which is an Other NLRX1-Related Disease,Disorder or Condition is a skin disease, disorder, or condition. In particular, in one aspect, thedisease, disorder, or condition is selected from psoriasis, cutaneous lupus erythematosus, dermatomyositis, pemphigoid, pemphigus, scleroderma, vasculitis, epidermolysis bullosa acquisita, vitiligo, lichen planus, scleritis, dermatitis, erythema nodosum, pyoderma gangrenosum, skin fissures, acne, enterocutaneous fistula, skin tags, canker sores, acrodermatitis enteropathica, pyoderma vegetans, leukocytoclastic vasculitis, anal fissures, Sweet’s syndrome, rosacea, alopecia, keratoderma blennorrhagica, rosacea, cold sores, urticaria, actinic keratosis, carbuncle, cellulitis, ichthyosis vulgaris, skin infection, malar rash, photosensitivity, livedo reticularis, livedo reticularis, oral and nasal ulcers, purpura, mucositis, hemorrhoids, burn, and sunburn. In view of the above, in one aspect of the invention, there is further provided a method foridentifying a substance useful for the prevention or treatment of a disease, disorder, orcondition associated with activation of the mPTP, which method comprises determiningwhether said substance (i) binds to NLRX1 and (ii) inhibits activity of the mPTP and, if it does,identifying said substance as a substance useful for the prevention or treatment of saiddisease, disorder, or condition associated with activation of the mPTP.Similarly, there is provided a substance which is (i) capable of binding to NLRX1 and (ii) capable of inhibiting the activity of the mPTP, for use in the prevention or treatment of adisease, disorder, or condition associated with activation of the mPTP. In particular, there isprovided a substance which (i) binds NLRX1 and (ii) inhibits the activity of the mPTP, for use in the prevention or treatment of a disease, disorder, or condition associated with activation of the mPTP. In a particular aspect of the present invention, there is provided a substancewhich is (i) capable of binding to NLRX1 and (ii) capable of inhibiting the activity of themPTP, which is identified by a method according to the present invention, for example a method described under the sub-heading ‘Methods for Identifying Substances for use according to the present invention’ below, for use in the prevention or treatment of a disease,disorder, or condition associated with activation of the mPTP. That is, there is provided asubstance which (i) binds NLRX1 and (ii) inhibits the activity of the mPTP, which is identified by a method according to the present invention, for example a method described under the sub-heading ‘Methods for Identifying Substances for use according to the present invention’ below, for use in the prevention or treatment of a disease, disorder, or condition associatedwith activation of the mPTP.Moreover, in view of the above, the present invention provides a method for identifying asubstance useful for the prevention or treatment of a disease, disorder, or condition which isan Other NLRX1-Related Disease, Disorder or Condition, which method comprises determining whether said substance (i) binds to NLRX1 and (ii) inhibits activity of the mPTP and, if it does, identifying said substance as a substance useful for the prevention or treatment of said disease, disorder, or condition which is an Other NLRX1-Related Disease, Disorder or Condition. Similarly, there is provided a substance which is (i) capable of binding to NLRX1 and (ii) capable of inhibiting the activity of the mPTP, for use in the prevention or treatment of a disease, disorder, or condition which is an Other NLRX1-Related Disease, Disorder or Condition. In particular, there is provided a substance which (i) binds NLRX1 and (ii) inhibits the activity of the mPTP, for use in the prevention or treatment of a disease, disorder, or condition which is an Other NLRX1-Related Disease, Disorder or Condition. In a particularaspect of the present invention, there is provided a substance which is (i) capable of bindingto NLRX1 and (ii) capable of inhibiting the activity of the mPTP, which is identified by a method according to the present invention, for example a method described under the sub- heading ‘Methods for Identifying Substances for use according to the present invention’ below, for use in the prevention or treatment of a disease, disorder, or condition which is an Other NLRX1-Related Disease, Disorder or Condition. That is, there is provided a substance which (i) binds NLRX1 and (ii) inhibits the activity of the mPTP, which is identified by a method according to the present invention, for example a method described under the sub- heading ‘Methods for Identifying Substances for use according to the present invention’ below, for use in the prevention or treatment of a disease, disorder, or condition which is an Other NLRX1-Related Disease, Disorder or Condition.Suitably, a substance which is (i) capable of binding to NLRX1 and (ii) capable of inhibitingthe activity of the mPTP, for use in the prevention or treatment of a disease, disorder, or condition associated with altered NLRX1 activity, is useful for the prevention or treatment of such a disease, disorder, or condition in a mammal, in particular a human. Therefore, asubstance which is (i) capable of binding to NLRX1 and (ii) capable of inhibiting the activity ofthe mPTP, for use in the prevention or treatment of a disease, disorder, or condition associated with altered NLRX1 activity, is suitably administered to a mammal, in particular a human. In another aspect of the present invention, there is provided a method for preventing or treating a disease, disorder, or condition associated with altered NLRX1 activity, comprising administering to a subject in need thereof a prophylactically or therapeutically effective amountof a substance which is (i) capable of binding to NLRX1 and (ii) capable of inhibiting the activityof the mPTP, for example wherein the substance which is (i) capable of binding to NLRX1 and(ii) capable of inhibiting the activity of the mPTP is identified by a method according to thepresent invention, for example a method described under the sub-heading ‘Methods for Identifying Substances for use according to the present invention’ below.In another aspect of the present invention, there is provided use of a substance which is (i)capable of binding to NLRX1 and (ii) capable of inhibiting the activity of the mPTP, for example wherein the substance which is (i) capable of binding to NLRX1 and (ii) capable of inhibiting the activity of the mPTP is identified by a method according to the present invention, for example a method described under the sub-heading ‘Methods for Identifying Substances for use according to the present invention’ below, in the manufacture of a medicament for preventing or treating a disease, disorder, or condition associated with altered NLRX1 activity. In any of the above-described aspects of the invention, substances which are capable ofbinding to NLRX1 suitably are substances capable of regulatory modulation of NLRX1, forexample activation or inhibition of NLRX1 activity (such as NLRX1 signalling activity),particularly inhibition of NLRX1 activity. Accordingly, the present invention suitably providessubstances which are (i) capable of binding to and inhibiting the activity of NLRX1, i.e.inhibitors of NLRX1, and (ii) capable of inhibiting the activity of the mPTP, for use in theprevention or treatment of a disease, disorder, or condition associated with altered NLRX1 activity, for example a disease, disorder, or condition, which is associated with activation ofthe mPTP or an Other NLRX1-Related Disease, Disorder or Condition.Methods for Identifying Substances for use according to the present invention As described above, the present invention relates to methods for identifying a substance useful for the prevention or treatment of a disease, disorder, or condition associated with altered NLRX1 activity, which method comprises determining whether said substance (i) binds to NLRX1 and (ii) inhibits activity of the mPTP and, if it does, identifying said substance as a substance useful for the prevention or treatment of said disease, disorder, or conditionassociated with altered NLRX1 activity. That is, the method of the present invention comprisesstep (i) of determining whether a substance binds to NLRX1, and step (ii) of determiningwhether a substance inhibits the activity of the mPTP.In one aspect, the method of the present invention is an in vitro method. In an alternative, lesspreferred, aspect, the method of the present invention is an in vivo method.In one aspect, the method of the present invention comprises step (i) of determining whether a substance binds to NLRX1, wherein the determination of whether a substance binds toNLRX1 is performed by means comprising a thermal shift assay of NLRX1 binding. Suitably,the thermal shift assay is a cellular thermal shift assay (CETSA). Therefore, in one aspect, thepresent invention provides an assay method for a substance that binds to NRLX1 which comprises means comprising a thermal shift assay of NLRX1 binding. For example, in one aspect, the present invention provides an assay method for a substance that binds to NRLX1which comprises means comprising a cellular thermal shift assay (CETSA) of NLRX1 binding. Typically, a thermal shift assay measures changes in the thermal denaturation temperature and hence stability of a protein under varying conditions, in particular drug / ligand concentration. Specifically, the binding of a drug / ligand may increase the thermal stability of atarget protein, as described in Koshland, 1958. Measuring the thermal shift of a protein maybe achieved via a number of techniques including differential scanning fluorimetry orthermofluor. In a cellular thermal shift assay (CETSA), protein thermal shift / melting curves aregenerated in intact cells. In particular, in a CETSA, denatured proteins, including a target protein, are aggregated and removed by centrifugation following lysis of intact cells. Stable proteins in the resultant supernatant can be identified via a number of techniques includingWestern Blotting, enzyme-linked immunosorbent assay (ELISA), or mass spectrometry.Therefore, suitably, the cellular thermal shift assay (CETSA) according to the present inventioncomprises:(i) contacting a test substance with cells expressing NLRX1 to produce a test sample;(ii) exposing the test sample to a stepwise heat challenge;(iii) calculating the Tm value of the test sample; and(iv) comparing the Tm value of the test sample to the Tm value of a control sample;wherein binding to NLRX1 is indicated by an increased Tm value of the test sample relative to the Tm value of a control sample. Suitably, step (ii) of exposing the test sample to a stepwise heat challenge comprises exposing samples to a 3 step, for example a 4 step, for example a 5 step, for example a 6 step, for example an 8 step, for example a 10 step, for example a 12 step heat challenge. For the avoidance of doubt, a stepwise heat challenge is a process by which a test sample, typically via separation into aliquots, is exposed to a series of specific temperatures within a defined range. For example, a 3 step heat challenge involves exposure of a test sample to 3 different temperatures within a defined range. Suitably, the heat challenge of step (ii) is performed between 40 and 100oC, such as between 45 and 85oC, such as between 50 and 75oC. Step (iii) of calculating the Tm value i.e. the temperature at which 50% of melting is achieved, of test samples, is performed firstly by quantifying the amount of melted NLRX1 in the test sample at each step of the stepwise heat challenge, plotting said amounts against temperature, and calculating the temperature at which 50% of melting is achieved. Indeed, the calculation of the Tm value is described in Binding Example 1 below. Therefore, suitably,step (iii) of calculating the Tm value of the test sample further comprises a process of WesternBlotting, in particular wherein NLRX1 (e.g. melted NLRX1) is targeted with an anti-NLRX1antibody and said anti-NLRX1 antibody is targeted with a secondary antibody conjugated to horseradish peroxidase. Suitably, the activity of the horseradish peroxidase, which represents the amount of NLRX1 (e.g. melted NLRX1) in a test sample, is measured viachemiluminescence. Alternatively, NLRX1 (e.g. melted NLRX1) is targeted with an anti-NLRX1 antibody and said anti-NLRX1 antibody is targeted with a secondary antibody conjugated to a dye, such as a fluorescent dye, in particular an infra-red or near-infra-red dye.Suitably, the fluorescence of the dye, such as the infra-red or near-infra-red dye, whichrepresents the amount of NLRX1 (e.g. melted NLRX1) in a test sample, is measured via infra- red fluorescence imaging. Suitably, step (iv) of comparing the Tm value of the test sample to the Tm value of a controlsample comprises comparison to a control sample to which no test substance was addedand / or comparison to a control sample to which vehicle, or an alternative known inactive test substance was added. Suitably, the Tm value of test samples is increased, relative to the control sample, by 0.5oC or more, such as by 0.75oC or more, such as by 1oC or more, such as by 1.2oC or more, such as by 1.5oC or more.A particularly suitable example of a cellular thermal shift assay (CETSA) is described in detailin NLRX1 Binding Example 1 below. Similarly, the utility of such a CETSA in identifying compounds that can bind to NLRX1 is demonstrated in NLRX1 Binding Example 1 below. In an alternative aspect, the method of the present invention comprises step (i) of determining whether a substance binds to NLRX1, wherein the determination of whether a substance bindsto NLRX1 is performed by means comprising a filtration binding assay of NLRX1 binding. Inone aspect, the present invention provides an assay method for a substance that binds toNRLX1 which comprises means comprising a filtration binding assay of NLRX1 binding.Typically, a filtration binding assay measures the binding affinity between two molecules bymeans of a method involving a filtration step which separates bound from unbound molecules.In one embodiment of such a filtration binding assay, a first molecule, typically a protein (andin this case NLRX1), is mixed with a second molecule, typically a ligand or DNA. The amount of ligand bound to the protein can then be quantified by filtration-based separation of the protein from the unbound ligand. The first molecule, i.e. protein, is retained on the filter following filtration and only the second molecule, i.e. ligand, bound to the first molecule, i.e. protein, is retained, whilst unbound second molecule, i.e. ligand, passes through the filter. The amount of second molecule, i.e. ligand, bound to the first molecule, i.e. protein, and therefore retained on the filter may be ascertained via mass spectrometry. Alternatively, this methodmay involve use of a radioisotope labelled second molecule, i.e. ligand (radioligand), withdetection achieved via liquid scintillation. Alternatively, the second molecule, i.e. ligand, may be fluorescently labelled and detection of bound ligand may be achieved via chemiluminescence. Upon evaluating the amount of second molecule, i.e. ligand bound to the first molecule, i.e. protein, at different concentrations of the second molecule, i.e. ligand, the binding affinity of the second molecule, i.e. ligand, for the first molecule, i.e. protein, can be determined.Alternatively a first molecule, typically a protein (and in this case NLRX1), is presented orplaced on a filter. Subsequently, the second test molecule, typically a ligand or DNA, is applied to the filter (in solution) and is only retained by the filter upon specific binding to the first molecule. This specific binding may be ascertained via a number of different techniques, suchas mass spectrometry or fluorescent labelling or radioisotope labelling and measurement vialiquid scintillation. Therefore, suitably, the filtration binding assay according to the present invention comprises: (i) contacting a test substance with NLRX1, to produce a test sample; (ii) filtering the test sample through a filter, on which NLRX1 is retained;(iii) detecting, and optionally quantifying, the amount of test substance which is retained onthe filter;wherein binding to NLRX1 is indicated by detection, and optional quantification, of testsubstance retained on the filter.Alternatively, the filtration binding assay according to the present invention comprises:(i) contacting a probe substance, which binds to NLRX1, with membranes on which NLRX1 ispresent; (ii) filtering test substances through a filter, in the presence of said membranes on whichNLRX1 is present; and(iii) detecting, and optionally quantifying, the amount of test substance binding to membraneson which NLRX1 is present, or detecting, and optionally quantifying, the amount of probesubstance displaced from binding to membranes on which NLRX1 is present;wherein binding to NLRX1 is indicated by detection, and optional quantification, of testsubstance binding to membranes on which NLRX1 is present or detection, and optionalquantification, of probe substance displaced from binding to membranes on which NLRX1 ispresent.Suitably, membranes on which NLRX1 is present are membranes expressing NLRX1, forexample which have been produced from cells expressing NLRX1. Alternatively, membranes on which NLRX1 is present are membranes onto which NLRX1 is attached. Suitably, step (ii) of filtering the test sample through a filter, on which NLRX1 is retained, orfiltering test substances through said membranes on which NLRX1 is present comprisesfiltration via centrifugation. Alternatively, step (ii) of filtering the test sample through a filter, onwhich NLRX1 is retained or filtering test substances through said membranes on which NLRX1is present comprises vacuum-based aspiration. Suitably, step (iii) of detecting, and optionally, quantifying the amount of test substance whichis retained on the filter is achieved via mass spectrometry, for example using a process ofliquid chromatography, for example, ultra high-performance liquid chromatography, inparticular using a C18 column; Poroshell 120 E-C18, Agilent, coupled to triple quadrupole mass spectrometer. The filter used in the aforementioned filtration binding assays may comprise glass fibre paper or nitrocellulose paper, in particular glass fibre paper. Alternatively, step (iii) of detecting, and optionally, quantifying the amount of test substance binding to membranes on which NLRX1 is present, or detecting, and optionally quantifying, the amount of probe substance displaced from binding to membranes on which NLRX1 ispresent comprises detecting, and optionally quantifying, the amount of probe substancedisplaced from binding to membranes on which NLRX1 is present. When step (iii) comprisesdetecting, and optionally quantifying, the amount of probe substance displaced from bindingto membranes on which NLRX1 is present, said step comprises a process of liquidchromatography, for example, ultra high-performance liquid chromatography, in particularusing a C18 column; Poroshell 120 E-C18, Agilent, coupled to triple quadrupole massspectrometer.Suitably, binding to NLRX1 is indicated by detection, and optional quantification, of testsubstance retained on the filter on which NLRX1 is retained. More suitably, binding to NLRX1is indicated by detection, and optional quantification, of an increased amount of test substanceretained on the filter on which NLRX1 is retained relative to a control sample. Suitably, acontrol sample used in the filtration binding assay described above is a sample to which no test substance was added or to which vehicle, or an alternative known inactive test substance was added. Suitably, binding to NLRX1 is detected, either via detection of an increased amount of test substance retained on the filter on which NLRX1 is retained at an amount that is in accordance with one or more of the suitable EC50, IC50, pIC50, and Ki values described below.Alternatively, binding to NLRX1 is indicated by detection, and optional quantification, of testsubstance binding to membranes on which NLRX1 is retained or is present. Alternatively,binding to NLRX1 is indicated by detection, and optional quantification, of probe substancedisplaced from binding to membranes on which NLRX1 is present. More suitably, binding toNLRX1 is indicated by detection, and optional quantification, of an increased amount of testsubstance binding to membranes on which NLRX1 is present or detection, and optionalquantification, of an increased amount of probe substance displaced from binding tomembranes on which NLRX1 is present, relative to a control sample. Suitably, a controlsample used in the filtration binding assay described above is a sample to which no testsubstance was added or to which vehicle, or an alternative known inactive test substance wasadded. Suitably, binding to NLRX1 is detected either via detection of an increased amount oftest substance binding to membranes on which NLRX1 is present or detection of an increased amount of probe substance displaced from binding to membranes on which NLRX1 is present, is specific binding to NLRX1. Suitably, said specific binding is identified via exposure of test substances to NLRX1 expressing membranes in the presence of an excess concentration of a competing compound, or via exposure of test substances to NLRX1 knock-out cell membranes, or via exposure of said test substances to alternative proteins to which they do not bind. Suitably, binding to NLRX1 is detected, either via detection of an increased amount of test substance binding to membranes on which NLRX1 is present or detection of an increased amount of probe substance displaced from binding to membranes on which NLRX1 is present, at an amount that is in accordance with one or more of the suitable EC50, IC50, pIC50, and Ki values described below.A particularly suitable example of a filtration binding assay is described in detail in NLRX1Binding Example 2 below. Similarly, the utility of such a filtration binding assay in identifyingcompounds that can bind to NLRX1 is demonstrated in NLRX1 Binding Example 2 below.In a further alternative aspect, the method of the present invention comprises step (i) of determining whether a substance binds to NLRX1, wherein the determination of whether asubstance binds to NLRX1 is performed by means comprising a proximity assay of NLRX1binding. Suitably, the proximity assay is a bioluminescence resonance energy transfer (BRET)assay, and in particular is a nano-BRET assay, of NLRX1 binding. Therefore, in one aspect, the present invention provides an assay method for a substance that binds to NRLX1 whichcomprises means comprising a proximity assay of NLRX1 binding. For example, in oneaspect, the present invention provides an assay method for a substance that binds to NRLX1which comprises means comprising a bioluminescence resonance energy transfer (BRET)assay, and in particular a nano-BRET assay, of NLRX1 binding. Typically, a proximity assay directly detects interaction of proteins, extracellular vesicles, and other cellular components. Specifically, two different primary antibodies are typically raised, indifferent animal species, against two proteins or cellular components of interest. In turn,secondary antibodies are raised which target the constant region of said primary antibodies. Each of the secondary antibodies is typically conjugated to a short, sequence-specific DNA molecule. When the two proteins or cellular components of interest are in close proximity, the DNA strands conjugated to the secondary antibodies can participate in rolling circle DNA synthesis upon subsequent addition of appropriate substrates and enzymes. When the DNA circle has been amplified via the rolling circle DNA synthesis, fluorescently labelled complementary oligonucleotides can be added, which binds to amplified DNA, and omit levels of fluorescence which may be detected. It will be understood that proximity assays may be adapted to use alternative mechanisms for generating fluorescent signals upon two proteins or cellular components of interest coming into close proximity. For example, one secondary antibody may be conjugated to a fluorophore donor, and the other secondary antibody may be conjugated to a fluorophore acceptor. A BRET assay is a specific example of a proximity assay which takes advantage of the natural phenomenon of dipole-dipole energy transfer from a luminescence donor to a fluorophoreacceptor. Typically, a first protein or cellular component of interest is conjugated to aluminescence donor, typically an enzyme such as luciferase, and a second protein or cellular component of interest is conjugated to a fluorophore acceptor, such as a fluorescent protein such as green-fluorescent protein (GFP), or yellow-fluorescent protein (YFP). When the two proteins or cellular components of interest come into close proximity, typically less than 10 nm, energy is transferred from the luminescence donor to the fluorophore acceptor, resulting in a fluorescent signal being produced. A nano-BRET assay is a further limitation to the BRET assay in which a smaller, brighter, and more stable luciferase (nano-luciferase) is used resulting in a high fluorescence emission intensity and improved spectral resolution, which in turn improves the sensitivity and range of existing BRET assays.Therefore, suitably, the BRET or nano-BRET assay according to the present inventioncomprises:(i) contacting a test substance with cells expressing an NLRX1-luciferase construct to producea test sample;(ii) contacting a tracer molecule, which comprises a substance known to bind to NLRX1 anda substance which is required for luciferase activity, with the test sample; and(iii) contacting luciferase substrate with the test sample; and(iv) quantifying the luciferase signal of the test sample; wherein binding to NLRX1 is indicated by a decrease in the luciferase signal relative to a control sample. Alternatively, suitably, the BRET or nano-BRET assay according to the present invention comprises: (i) contacting a test substance with cells expressing an NLRX1-luciferase construct to produce a test sample; (ii) contacting a tracer molecule, which comprises a substance known to bind to NLRX1 and a substance which is required for luciferase activity, with the test sample; and (iii) contacting luciferase substrate with the test sample; and(iv) quantifying the light emission signal of the NLRX1-luciferase test sample and thefluorescence of the tracer molecule; wherein binding to NLRX1 is indicated by a change in the BRET ratio relative to a control sample. Suitably, a control sample used in the BRET or nano-BRET assay described above is asample to which no test substance was added or to which vehicle, or an alternative knowninactive test substance was added. Suitably, cells expressing an NLRX1-luciferase construct are provided via transfection of cells with an NLRX1-luciferase construct comprising NLRX1 conjugated to luciferase, such as a nano-luciferase, at the C-terminus. Suitably, the tracer molecule of step (ii) comprises a substance known to bind to NLRX1 conjugated via click chemistry to NanoBRETTM 590-Azide-C3 (Promega). The NanoBRETTM 590-Azide-C3 reagent, uses thereof, and assays using said reagents, are further described, in addition to further suitable reagents, in US Patent No. 10,024,862, US Patent No. 10,067,149, and EP2932267, each of which is herein incorporated by reference in its entirety.Suitably a BRET or nano-BRET assay according to the present invention, in particular whereinsaid assay utilises the NanoBRETTM 590-Azide-C3 (Promega) reagent, is performed in accordance with the assays described in one or more of US Patent No.10,024,862, US Patent No.10,067,149, and EP293226. Suitably, step (iv) of quantifying the light emission of the luciferase signal of the test sample and / or the fluorescence of the tracer molecule is performed using a CLARIOstar reader.Suitably, step (iv) of quantifying the light emission of the luciferase signal of test samplesand / or the fluorescence of the tracer molecule is performed via detection at a wavelength of about 470 nm and about 615 nm in order to calculate the BRET ratio (acceptor ca 615 nm emission / donor ca 470 nm emission). A particularly suitable example of a nano-BRET assay is described in detail in NLRX1 Binding Example 3 below. Similarly, the utility of such a nano-BRET assay in identifying compounds that can bind to NLRX1 is demonstrated in NLRX1 Binding Example 3 below. In one aspect, the method of the present invention comprises step (ii) of determining whether a substance inhibits the activity of the mPTP, wherein the determination of whether a substance inhibits the activity of the mPTP is performed by means comprising a mitochondrial calcium retention assay. In particular, pharmacological inhibition or modulation of the mPTP can be measured in such a mitochondrial calcium retention assay since, in vitro, isolated mitochondria rapidly sequesterexogenous calcium (Ca2+) until the intramitochondrial Ca2+ concentration reaches thethreshold for mPTP activation. Once the pore is activated, mitochondrial integrity iscompromised and the stored Ca2+ is released. The distribution of Ca2+ between extra- andintra-mitochondrial compartments can be measured in real time with the use of membrane- impermeant Ca2+sensitive fluorescent dyes. Depending on the configuration of the assay, inhibition or modulation of the mPTP either delays the opening of the pore or increases the concentration of Ca2+required to induce mPTP opening. In one aspect, the mitochondrial calcium retention assay is a rat liver mitochondrial calcium retention assay. In an alternative aspect, the mitochondrial calcium retention assay is a rat brain mitochondrial calcium retention assay. In a further aspect, the mitochondrial calcium retention assay is human platelet mitochondrial calcium retention assay. See, for example, the rat liver mitochondria and rat brain mitochondria assays disclosed in WO2023 / 166303 within Biological Example 1 of that document (which is herein incorporated by reference in its entirety) and see General Methods below. When the mitochondrial calcium retention assay is a rat liver mitochondrial calcium retention assay, mitochondria are suitably isolated from female rats, such as female Sprague Dawley rats, using the following method:Cervical dislocation is performed on the female rat, prior to perfusing the liver of said femalerat, in situ, with between 20 and 60 mL, such as between 30 and 50 mL, such as about 40 mL of a saline solution, and preferably Dulbecco’s Phosphate Buffered Saline (DPBS). The liver is subsequently dissected and transferred into between 10 and 50 mL, such as between 20and 40 mL, such as about 30 mL, of an isolation buffer, suitable examples of which are knownto the skilled person. A particularly suitable isolation buffer comprises 250 mM sucrose, 10 mM potassium chloride, 1 mM ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraaceticacid (EGTA), 1 mM ethylene diaminetetraacetic acid (EDTA), and 25 mM HEPES, whereinthe pH of said isolation buffer is adjusted to 7.5 using 1 M sodium hydroxide. The liver is thenremoved from the buffer and minced into pieces of between 1 and 10 mm, in particular about 5 mm, prior to transfer into a homogenization tube, such as a 50 mL Potterton douncehomogenization tube, comprising between 10 and 50 mL, such as about 30 mLhomogenization / centrifugation buffer, suitable examples of which are known to the skilledperson. A particularly suitable homogenization / centrifugation buffer comprises 300 mM trehalose, 25 mM HEPES, 1 mM EGTA, 1 mM EDTA, and 10 mM potassium chloride, wherein the pH of said homogenization / centrifugation buffer is adjusted to 7.5 using 1 M sodium hydroxide, and wherein said homogenization / centrifugation buffer is supplemented with 0.1% bovine serum albumin (BSA) and complete protease inhibitor cocktail (one tablet per 50 mL buffer). Homogenization is suitably carried out using a Teflon® pestle at between 1500 and2500 rpm, such as 1600 and 2000 rpm, such as at about 1800 rpm. Subsequently, thehomogenization product is centrifuged at between 500 and 1500 g, such as between 600 and 100 g, such as at about 800 g, for between 1 and 20 minutes, such as between 2 and 16 minutes, such as between 5 and 15 minutes, such as for about 10 minutes, at a temperatureof 1-10oC, such as 2-8oC, such as 2-5oC, such as at about 4oC. In turn, the resultingsupernatant was centrifuged at between 5000 and 20000 g, such as between 6000 and 16000 g, such as between 8000 and 12000 g, such as at about 10000 g, for between 1 and 20 minutes, such as between 2 and 16 minutes, such as between 5 and 15 minutes, such as forabout 10 minutes, at the same temperature as above. Finally, the resultant pellet was washedonce with an assay buffer, suitably FLIPR assay buffer comprising 75 mM mannitol, 25 mM sucrose, 5 mM potassium phosphate monobasic, 20 mM Tris, 100 mM potassium choride, and 0.1% BSA, adjusted to pH 7.4 using hydrochloric acid, before being centrifuged again and subsequently resuspended in said assay buffer, in particular FLIPR assay buffer, to a target protein concentration of between 5 and 15 mg / mL, such as 6 and 12 mg / mL, such as 7.5 to 10 mg / mL, and most preferably of about 8.8. mg / mL. When the mitochondrial calcium retention assay is a rat brain mitochondrial calcium retention assay, mitochondria are suitably isolated from rats, such as female rates, such as female Sprague Dawley rats, using the following method: Anaesthetized rats, which may be performed via methods known in the art, are suitablyperfused, in situ, with between 20 and 60 mL, such as between 30 and 50 mL, such as about40 mL of a saline solution, and preferably Dulbecco’s Phosphate Buffered Saline (DPBS). The brain is subsequently dissected and transferred into between 10 and 50 mL, such as between 20 and 40 mL, such as about 30 mL, of an isolation buffer, suitable examples of which are known to the skilled person. A particularly suitable isolation buffer comprises 225 mM mannitol, 75 mM sucrose, and 1 mM ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA), wherein the pH of said isolation buffer is adjusted to 7.4 using 1 Msodium hydroxide. The brain is then removed from the buffer and minced into pieces ofbetween 1 and 10 mm, in particular about 5 mm, prior to transfer into a homogenization tube, such as a 50 mL Potterton dounce homogenization tube, comprising between 5 and 25 mL, such as about 10 mL homogenization / centrifugation buffer, suitable examples of which ware known to the skilled person. A particularly suitable homogenization / centrifugation buffer comprises 300 mM trehalose, 25 mM HEPES, 1 mM EGTA, 1 mM EDTA, and 10 mM potassium chloride, wherein the pH of said homogenization / centrifugation buffer is adjusted to 7.5 using 1 M sodium hydroxide, and wherein said homogenization / centrifugation buffer is supplemented with 0.1% bovine serum albumin (BSA) and complete protease inhibitor cocktail(one tablet per 50 mL buffer). Homogenization is suitably carried out using a Teflon® pestleat between 1500 and 2500 rpm, such as 1600 and 2000 rpm, such as at about 1800 rpm. Subsequently, the homogenization product is centrifuged at between 500 and 5000 g, such as between 1000 and 2500 g, such as at about 2000 g, for between 1 and 20 minutes, such as between 2 and 16 minutes, such as between 5 and 15 minutes, such as for about 10 minutes, at a temperature of 1-10oC, such as 2-8oC, such as 2-5oC, such as at about 4oC. In turn, the resulting supernatant was centrifuged at between 5000 and 20000 g, such as between 6000 and 16000 g, such as between 8000 and 14000 g, such as at about 12000 g, for between 1 and 20 minutes, such as between 2 and 16 minutes, such as between 5 and 15minutes, such as for about 9 minutes, at the same temperature as above. Finally, the resultantpellet is suitably resuspended in an isolation buffer, for example as described above, but with the further addition of about 0.02% digitonin, prior to centrifugation at between 5000 and 20000 g, such as between 6000 and 16000 g, such as between 8000 and 14000 g, such as at about 12000 g, for between 1 and 20 minutes, such as between 2 and 16 minutes, such as between 5 and 15 minutes, such as for about 11 minutes, at the same temperature as above, followed by subsequent resuspension in 1-10 mL, such as 2-8 mL, such as about 5 mL, isolation buffer, preferably wherein the isolation buffer has the composition described above but wherein the EGTA concentration is reduced to about 0.1 mM. When the mitochondrial calcium retention assay is a rat liver mitochondrial calcium retention assay, or is a rat brain mitochondrial calcium retention assay, test substances are prepared,typically from stocks in 10 mM dimethyl sulfoxide (DMSO), via serial dilution in DMSO in half-log steps to produce a desire number of test concentrations, suitably in the range 30 µM to 1 nM. Simultaneously, an intermediate dilution of 1-10 µL, such as about 5 µL, of DMSO samples in 50-500 µL, such as 100-400 µL, such as 200-300µL, or about 250 µL, assay buffer. Suitable assay buffers are known to the skilled person and may include FLIPR assay buffer, which has the composition described above.5 µL samples were then added into duplicatedwells of a multi-well plate, preferably a 384-well plate. Control wells may suitably contain 0.5%(v / v) DMSO and 5 µM cyclosporin A. Next, a stock assay solution was prepared via addition of 0.1-2 mL, such as 0.5 -1.5 mL, such as about 1 mL, of the mitochondrial sample solution(derived from liver or brain) to 2-10 mL, such as 4-8 mL, such as 5-6 mL, and in particularabout 5.6 mL, assay buffer. Suitably, in particular when the mitochondria sample is a rat livermitochondria sample, the assay buffer is FLIPR assay buffer with the composition describedabove supplemented with 10 mM succinate disodium salt, 1 µM rotenone and 2 µM Fluo5Npentapotassium salt (Invitrogen). Suitably, in particular when the mitochondria sample is a ratbrain mitochondria sample, the assay buffer is comprises 120 mM mannitol, 40 mM MOPS, 5 mM monopotassium phosphate, 60 mM potassium chloride, 10 mM pyruvate, 2 mM malate, 2 mM magnesium chloride, 20 µM ADP, 1.26 µM oligomycin A, supplemented with 2 µMFluo5N pentapotassium salt (Invitrogen). A 5-25 µL, such as 15 µL, sample is then transferredinto the wells of the multi-well plate (which also contain the test substances), prior to incubation for between 1 and 20 minutes, such as between 5 and 15 minutes, such as for about 10minutes, at room temperature. Multi-well plates are then transferred to a plate reader, aparticularly suitable example of which is a FLIPR® Tetra Plate Reader. Dye fluorescence is suitably read every 1 to 5 seconds, such as 3 seconds, for between 1 and 20 minutes, such as between 5 and 15 minutes, such as for about 10 minutes. After 10 to 15 seconds, and most suitably 12 seconds, a 1-5 µL, such as 2.5 µL, bolus of calcium chloride (75 µM) was added from a source comprising calcium chloride, in particular at a concentration of 675 µM, in assaybuffer, preferably FLIPR assay buffer. When the mitochondrial calcium retention assay is a human platelet mitochondrial calcium retention assay, it should be noted that the assay is instead performed using a mitochondrial membrane potential flow cytometry assay in stimulated human platelets, since stimulation of platelets results in the rapid influx of Ca2+across the platelet membrane. Subsequently, Ca2+is sequestered by mitochondria until the threshold for mPTP opening is reached, at which point the pore opens and the mitochondrial membrane potential is dissipated. Changes in mitochondria membrane potential due to mPTP opening can be quantified in live platelets using standard mitochondrial membrane potential dyes e.g. 3,3’-dihexyloxacarbocyanine Iodide; DiOC6(3), enabling pharmacological characterisation of mPTP inhibitors. When the mitochondrial calcium retention assay is a human platelet mitochondrial calcium retention assay, human platelets are suitably harvested and isolated using the following method: A volume of human blood, typically between 5-50 mL, such as 10-40 mL, such as 15-25 mL, such as about 20 mL, is collected from a consenting donor, and added to a solution of sodiumcitrate, in particular 3.2% sodium citrate. The sample is centrifuged at between 10 and 500 g,such as between 50 and 400 g, such as between 100 and 300 g, such as about 200 g, for between 5 and 30 minutes, such as between 10 and 25 minutes, such as for about 20 minutes,at room temperature. The platelet rich plasma layer is then transferred to a new, i.e. clean,vessel. Prostaglandin 12 is added to the platelet sample at a concentration of 1-40 ng / mL,such as 5-30 ng / mL, such as 10-25 ng / mL, such as about 20 ng / mL. Next, the sample iscentrifuged at between 100 and 1000 g, such as between 200 and 800 g, such as between 500 and 750 g, such as at about 640 g, for between 1 and 20 minutes, for example 5 to 15 minutes, for example for about 10 minutes. The resultant pellet is resuspended in 1-10 mL,such as 2-5 mL, such as about 4 mL, of an assay buffer, and preferably HEPES buffer whichcomprises 137 mM sodium chloride, 2.7 mM potassium chloride, 11.9 mM sodium bicarbonate, 0.42 mM monosodium phosphate, 1 mM magnesium chloride, 5.5 mM glucose, 0.1% BSA, and 10 mM HEPES, adjusted to pH 7.4, before storage on ice. When the mitochondrial calcium retention assay is a human platelet mitochondrial calcium retention assay test substances are prepared, typically from stocks in 10 mM DMSO, via serialdilution into an assay buffer, examples of which are known to the skilled person, suitablycomprising 0.1-0.5%, such as about 0.4%, DMSO, prior to addition of 10-50 µL, such as 20-30 µL, such as about 25 µL samples to wells of a multi-well plate, preferably a 96-well plate.Simultaneously, human platelet samples were incubated with the mitochondrial membranepotential dye DiOC6(3) (3,3’-dihexyloxacarbocyanine Iodide; Invitrogen) at a concentration of 10-500 nM, such as 20-400 nM, such as 50-300 nM, such as 100-250 nM, such as about 200 nM, for between 5 and 60 minutes, for example between 15 and 45 minutes, for example for about 30 minutes, prior to addition of 5-250 µL, such as 10-100 µL, such as 20-80 µL, such as 40-60 µL, such as about 50 µL, of the platelet sample to each well of a multi-well plate, preferably a 96-well plate. Control wells may suitably contain 0.1% DMSO only, or 5 µM cyclosporin A. The wells were incubated for between 5 and 30 minutes, such as between 10 and 20 minutes, such as for about 15 minutes. Next, platelets were stimulated upon the addition of an assay buffer, suitable examples of which are known by the skilled person, further comprising calcium chloride, alpha thrombin, and convulxin to achieve final concentrations of1-5 nM, e.g. 2 nM calcium chloride; 0.01 to 0.03, e.g. about 0.017 U / mL alpha thrombin; and0.1 to 0.3, e.g. about 0.167 µg / mL convulxin. The samples were incubated for between 1 and 20 minutes, such as between 5 and 18 minutes, such as between 10 and 15 minutes, forexample for about 14 minutes before the reaction was then stopped upon addition of 5-50 µL,such as 10-40 µL, such as 20-30 µL, such as about 25 µL, EDTA, suitably at a concentration of 5-25 mM, such as 10-20 mM, such as about 15 mM. The mitochondrial membrane potential across the population of platelets is suitably quantified via flow cytometry, for example usinga Guava® easyCyte 5 Benchtop Flow Cytometer, with 1000 to 5000, such as 2000 to 4000,such as about 3000 events per well. In one aspect, the method of the present invention comprises step (i) of determining whether a substance binds to NLRX1, wherein the determination of whether a substance binds to NLRX1 is performed by means comprising a thermal shift assay of NLRX1 binding, and step (ii) of determining whether a substance inhibits the activity of the mPTP, wherein the determination of whether a substance inhibits the activity of the mPTP is performed by meanscomprising a mitochondrial calcium retention assay. In a further aspect, the method of thepresent invention comprises step (i) of determining whether a substance binds to NLRX1, wherein the determination of whether a substance binds to NLRX1 is performed by means comprising a thermal shift assay of NLRX1 binding, wherein the thermal shift assay is a cellular thermal shift assay (CETSA), and step (ii) of determining whether a substance inhibits the activity of the mPTP, wherein the determination of whether a substance inhibits the activity of the mPTP is performed by means comprising a mitochondrial calcium retention assay. In another aspect, the method of the present invention comprises step (i) of determining whether a substance binds to NLRX1, wherein the determination of whether a substance bindsto NLRX1 is performed by means comprising a filtration binding assay of NLRX1 binding, andstep (ii) of determining whether a substance inhibits the activity of the mPTP, wherein the determination of whether a substance inhibits the activity of the mPTP is performed by means comprising a mitochondrial calcium retention assay. In a further aspect, the method of the present invention comprises step (i) of determining whether a substance binds to NLRX1, wherein the determination of whether a substance bindsto NLRX1 is performed by means comprising a proximity assay of NLRX1 binding, and step(ii) of determining whether a substance inhibits the activity of the mPTP, wherein the determination of whether a substance inhibits the activity of the mPTP is performed by meanscomprising a mitochondrial calcium retention assay. In a particular aspect, the method of thepresent invention comprises step (i) of determining whether a substance binds to NLRX1, wherein the determination of whether a substance binds to NLRX1 is performed by meanscomprising a proximity assay of NLRX1 binding, wherein the proximity assay is abioluminescence resonance energy transfer (BRET) assay, and step (ii) of determining whether a substance inhibits the activity of the mPTP, wherein the determination of whether a substance inhibits the activity of the mPTP is performed by means comprising a mitochondrialcalcium retention assay. In a particularly preferred aspect, the method of the present inventioncomprises step (i) of determining whether a substance binds to NLRX1, wherein the determination of whether a substance binds to NLRX1 is performed by means comprising a proximity assay of NLRX1 binding, wherein the proximity assay is a nano-BRET assay, and step (ii) of determining whether a substance inhibits the activity of the mPTP, wherein the determination of whether a substance inhibits the activity of the mPTP is performed by means comprising a mitochondrial calcium retention assay.Suitably, the mitochondrial calcium retention assay of any of the above aspects is a rat livermitochondrial calcium retention assay, or a rat brain mitochondrial calcium retention assay, or a human platelet mitochondrial calcium retention assay. Characteristics of Substances for use according to the present invention As noted above, the present invention provides for substances which are (i) capable of binding to NLRX1 and (ii) capable of inhibiting the activity of the mPTP, for use in the treatment of disease, disorder, or condition associated with altered NLRX1 activity, and methods for identifying said substances.As used herein, the term a substance which inhibits mPTP activity, a substance with mPTPinhibitory activity, or an mPTP inhibitor, or variations thereof, may be defined as any moleculeswhich are able to directly inhibit the activity of the mPTP via any direct interaction with the mPTP. These substances also include substances which directly inhibit the activity of cellularcomponents which function upstream or downstream of the mPTP, consequently inhibitingmPTP activity. Inhibitors of mPTP activity, include substances which directly or indirectly inhibitthe activity or function, or the expression of the mPTP or any upstream or downstreamcomponents. In particular, inhibitors, of the mPTP may directly or indirectly inhibit the activityor function of the mPTP. In one aspect of the invention, the substance which is (i) capable of binding to NLRX1 and (ii)capable of inhibiting the activity of the mPTP is a modulator of NLRX1, for example an activatoror an inhibitor of NLRX1 activity (such as NLRX1 signalling activity), in particular an inhibitorof NLRX1 activity.As used herein, the terms a substance which modulates, activates, or inhibits nucleotide-binding oligomerization domain, leucine rich repeat containing X1 protein (NLRX1) activity, asubstance with NLRX1 modulatory, activatory, or inhibitory activity, or an NLRX1 modulator,activator, or inhibitor, or variations thereof, may be defined as any molecules which are ableto directly modulate, activate, or inhibit the activity of NLRX1 through interaction with NLRX1.These molecules are to be differentiated from indirect modulators, activators, or inhibitors of NLRX1, that is molecules which directly modulates, activate, or inhibit the activity of cellularcomponents which function upstream or downstream of NLRX1, consequently modulating,activating, or inhibiting NLRX1 activity. Modulators, activators, or inhibitors of NLRX1 activity,include molecules which directly modulate, activate, or inhibit the activity or function, or theexpression of NLRX1. In particular, modulators, activators, or inhibitors, of NLRX1 directlymodulate, activate, or inhibit the activity or function of NLRX1. Modulators, activators, or inhibitors of NLRX1 activity will thus bind NLRX1, typically non-covalently.In one aspect of the invention, the substance which is (i) capable of binding to NLRX1 and (ii)capable of inhibiting the activity of the mPTP, for example which is suitably identified by amethod according to the present invention, is a small molecule.As used herein, the term “small molecule” defines a molecule with a molecular weight of about 1500 g / mol or less, for example about 1200 g / mol or less, for example about 1000 g / mol orless, such as about 900 g / mol or less, such as about 800 g / mol or less, such as about 750g / mol or less. Typically, a small molecule has a molecular weight of about 50 g / mol or more,for example about 100 g / mol or more, for example about 150 g / mol or more, for example about200 g / mol or more, such as about 250 g / mol or more, such as about 300 g / mol or more. Therefore, a small molecule may have a molecular weight of about 50-1500 g / mol, for example about 100-1500 g / mol, for example about 200-1200 g / mol, for example about 250-1000 g / mol. The half maximal effective concentration EC50 is a measure of the concentration of a drug required to induce a particular biological or biochemical response. Specifically, EC50 is a quantitative measure that indicates how much of a substance is needed to obtain 50% of a given biological response, for example NLRX1 binding.In one aspect of the invention, a substance which is (i) capable of binding to NLRX1 and (ii)capable of inhibiting the activity of the mPTP, binds to NLRX1 with an EC50 value of less than about 100 µM, for example less than about 75 µM, for example less than about 50 µM, for example less than about 25 µM, for example less than about 15 µM, or less than about 10 µM.For example, the substance suitably binds to NLRX1 with an EC50 value of 0.000001-100 µM,such as 0.000001-75 µM, such as 0.000001-50 µM, such as 0.00001-50 µM, 0.0001-50 µM, 0.001-50 µM, 0.01-50 µM, 0.1-50 µM or 1-50 µM.The half maximal inhibitory concentration (IC50) is a measure of the potency of a substancein inhibiting a biological or biochemical function. Specifically, IC50 is a quantitative measurethat indicates how much of a substance is needed to inhibit, in vitro, a given biological processor biological component, for example mPTP activity, by 50%. In competition binding assays,the IC50 value is the concentration of competing substance that is required to displace 50% of the specific binding of a probe molecule, such as a radioligand, which may be measured via, for example, liquid scintillation. The pIC50 value is the negative log of the IC50 value of an inhibitor, and this logarithmic measure may be used since it more accurately reflects the logarithmic nature of potency values / concentrations. For example, an IC50 value of 1 µM corresponds to a pIC50 of 6.In one aspect of the invention, a substance which is (i) capable of binding to NLRX1 and (ii)capable of inhibiting the activity of the mPTP, binds to NLRX1 with a pIC50 value of greater than about 4.0, for example greater than about 5.0, in particular greater than about 6.0, forexample greater than about 7.0. For example, the substance suitably binds to NLRX1 with apIC50 value between 4.0 and 9.0, such as between 5.0 and 9.0, such as between 5.5 and 9.0, such as between 5.5 and 8.5, such as between 6.0 and 8.0.In a further aspect of the invention, a substance which is (i) capable of binding to NLRX1 and(ii) capable of inhibiting the activity of the mPTP, inhibits the activity of the mPTP with a pIC50value of greater than about 4.0, for example greater than about 5.0, in particular greater thanabout 6.0, for example greater than about 7.0. For example, the substance suitably inhibitsthe activity of the mPTP with a pIC50 value between 4.0 and 9.0, such as between 5.0 and 9.0, such as between 5.5 and 9.0, such as between 5.5 and 8.5, such as between 6.0 and 8.0. Related to a given IC50 value is the inhibition constant, Ki, which is an absolute value specifying the concentration of competing substance in a competition binding assay which would occupy 50% of a binding target, e.g. NLRX1, if no other binding partners were present.In one aspect of the invention, the substance which is (i) capable of binding to NLRX1 and (ii)capable of inhibiting the activity of the mPTP, binds to NLRX1 with a Kivalue of less than about 500 nM, for example less than about 250 nM, for example less than about 200 nM, for example less than about 100 nM, for example less than about 75 nM, for example less than about 50nM, less than about 25 nM, or less than about 10 nM. For example, the substance suitablybinds to NLRX1 with a Kivalue of 0.000001-500 nM, such as 0.000001-250 nM, such as 0.000001-100 nM, such as 0.00001-100 nM, 0.0001-100 nM, 0.001-100 nM, 0.01-100 nM, 0.1-100 nM or 1-100 nM.In addition to the above-described properties, a substance which is (i) capable of binding toNLRX1 and (ii) capable of inhibiting the activity of the mPTP, which is suitably identified by a method according to the present invention, may suitably have one or more of any of the following advantageous properties: -low inhibition of cytochrome P450 enzymes, such as CYP3A4 and / or CYP2D6;- adequate solubility and / or low intrinsic clearance (CLint) and / or low efflux bymulti-drug resistance protein 1 (MDR1) resulting in e.g. high oral bioavailability and / or high systemic exposure and / or high brain penetration.Suitably, a substance which is (i) capable of binding to NLRX1 and (ii) capable of inhibitingthe activity of the mPTP, to be useful for the prevention or treatment of a disease, disorder, orcondition associated with altered NLRX1 activity, is administered to a patient in an amountsuch that the dose of the substance is from about 0.1 mg to about 10000 mg per day, forexample from about 0.2 mg to about 8000 mg per day, for example from about 0.5 mg to about5000 mg per day. In particular, the dose of the substance is suitably from about 1 mg to about5000 mg per day, for example from about 5 mg to about 5000 mg per day, for example from about 10 mg to about 5000 mg per day. Novel Uses of Known Inhibitors of mPTP Activity As noted above, the present invention also provides known inhibitors of mPTP activity, for use in the prevention or treatment of a disease, disorder, or condition associated with alteredNLRX1 activity. In particular, the present invention provides known inhibitors of mPTP activity,for use in the prevention or treatment of a disease, disorder, or condition associated which is an Other NLRX1-Related Disease, Disorder or Condition. Suitable diseases, disorders or conditions which are Other NLRX1-Related Diseases,Disorders or Conditions are described above, but are not limited to those specified, under theheading “Conditions to be Treated”. Substances that are Known Inhibitors of mPTP Activity The term “alkyl” as used herein, such as in C1-3alkyl, is a straight or branched fully saturated hydrocarbon chain containing the specified number of carbon atoms. Examples of C1-3alkyl groups include methyl, ethyl, n-propyl and iso-propyl. Reference to “propyl” includes n-propyland iso-propyl. Reference to “butyl” includes n-butyl, iso-butyl, tert-butyl and sec-butyl. Memeans methyl. Et means ethyl. Pr means propyl. Bu means butyl. The term “alkylthio” as used herein, such as “C1-3alkylthio” refers to an alkyl group (e.g. a C1- 3alkyl group) as defined above singularly bonded to a sulphur atom e.g. -S-C1-3alkyl. Examples of C1-3alkylthio include methylthio, ethylthio and propylthio. The term “alkylene” as used herein, such as C1-4alkylene, whether alone or forming part of a larger group e.g. C1-4alkylene(aryl), C1-4alkylene(OH), C1-4alkylene(C3-6cycloalkyl), OC1- 4alkylene(C3-6cycloalkyl), C1-4alkylene(4-10 membered heterocycloalkyl), OC1-4alkylene(4-10 membered heterocycloalkyl), C1-4alkoxy, OC1-4alkylene(aryl), C1-4alkyleneOC1-4alkyl, C1- 4alkyleneOC3-6cycloalkyl, C1-4alkyleneO(4-10 membered heterocycloalkyl),C1- 4alkyleneO(aryl) or C1-4alkyleneO(C3-6alkynyl), e.g. C1-4alkylene(aryl), C1-4alkylene(OH), C1- 4alkylene(C3-6cycloalkyl), C1-4alkylene(4-10 membered heterocycloalkyl), C1-4alkoxy, OC1- 4alkylene(aryl), C1-4alkyleneOC1-4alkyl, C1-4alkyleneOC3-6cycloalkyl, C1-4alkyleneO(4-10 membered heterocycloalkyl), C1-4alkyleneO(aryl) or C1-4alkyleneO(C3-6alkynyl), is a bifunctional straight or branched fully saturated hydrocarbon group containing the specified number of carbon atoms. Examples of C1-4alkylene groups include methylene (i.e. -CH2-), ethylene (i.e. -CH2CH2-) n-propylene (i.e. (-CH2)3-) and n-butylene (i.e. (-CH2)4-). A branched example of a C1-4alkylene group is i-propylene (i.e. -CH(Me)CH2-). The term “alkynyl” as used herein, such as in C2-3alkynyl, is a straight or branched divalent hydrocarbon chain with a least one carbon-carbon triple bond. Examples of C2-3alkynyl include ethynyl, 1-propynyl and 2-propynyl.The term ‘alkenyl’ as used herein, such as in C2-6alkenyl, refers to a straight or branchedhydrocarbon group containing the specified number of carbon atoms and at least one carbon- carbon double bond, such as one or two double bonds. The term encompasses, CH=CH2, CH2CH=CH2, CH=CHCH3, CH2CH2CH=CH2, CH=CHCH2CH3, CH2CH=CHCH3, CH2CH2CH2CH=CH2, CH=CHCH2CH2CH3, CH2CH=CHCH2CH3, CH2CH2CH=CHCH3, CH=CHCH=CHCH3and CH2CH=CHCH=CH2. Branched variants such as CH(CH3)CH=CH2and CH=C(CH3)2are also included. The term ‘haloalkenyl’ as used herein, such as in C2-6haloalkenyl is a straight or a branched alkenyl chain containing the specified number of carbon atoms and at least one halogen atom, such as fluoro or chloro, for example fluoro. The term “alkoxy” as used herein, such as in C1-3alkoxy, refers to an alkyl group (e.g. a C1- 3alkyl group) as defined above, singularly bonded to an oxygen atom. Examples of C1-3alkoxy groups include methoxy, ethoxy, 1-propoxy and 2-propoxy, especially methoxy. The term “cycloalkyl” as used herein, such as in C3-5cycloalkyl or C3-6cycloalkyl, is a fully saturated hydrocarbon ring containing the specified number of carbon atoms, such as 3 to 5 or 3 to 6. Examples of C3-6cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, in particular cyclopropyl. Optionally, the cycloalkyl may be substituted as defined herein. The term “heterocycloalkyl” as used herein, such as in 4-10 membered heterocycloalkyl (e.g. 4-7 membered heterocycloalkyl), whether alone or forming part of a larger group such as C1- 4alkylene(4-10 membered heterocycloalkyl) and C1-4alkyleneO(4-10 membered heterocycloalkyl), is a fully saturated hydrocarbon ring containing the specified number of carbon atoms, wherein at least one of the carbon atoms is replaced by a heteroatom such asN, S or O. Optionally, the heterocycloalkyl may be substituted as defined herein. Aheterocycloalkyl group may be monocyclic. Alternatively, a heterocycloalkyl group may bepolycyclic such as a fused bicyclic or a bridged bicyclic ring system. In some examples a heterocycloalkyl group may incorporate a fused ring. In some examples a heterocycloalkyl group may incorporate a bridged ring. In some examples a bicyclic heterocycloalkyl group is spirocyclic i.e. a bicyclic cycloalkyl group wherein the two rings are connected through just one atom. The rings can be different or identical. Examples of 4-10 membered heterocycloalkyl groups include those comprising one heteroatom such as containing one heteroatom (e.g. nitrogen) or containing two or more heteroatoms (such as two heteroatoms e.g. two nitrogen atoms or one nitrogen atom and one oxygen atom). Examples of 4-10 membered heterocycloalkyl groups containing one nitrogen atom include azetidinyl, pyrrolidinyl, piperidinyl and azepanyl. Examples of 4-10 membered heterocycloalkyl groups containing two nitrogen atoms include diazetidinyl, imidazolidinyl, pyrazolidinyl, diazinanyl, and diazepanyl. Other examples of 4-10 membered heterocycloalkyl groups include oxetanyl, thietanyl, dioxetanyl, dithietanyl, tetrahydrofuranyl, tetrahydrothiophenyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, tetrahydropyranyl, thianyl, morpholinyl, thiomorpholinyl, dioxanyl, dithianyl, triazinanyl, trioxanyl, trithianyl, oxepanyl, and thiepanyl.As used herein, the term “heterocycle” means a non-aromatic cyclic group of carbon atomswherein from one to four of the carbon atoms is / are replaced by one or more heteroatoms independently selected from nitrogen (N), oxygen (O) or sulfur (S). A heterocycle group may, for example, be monocyclic or bicyclic. In a bicyclic heterocycle group there may be one or more heteroatoms in each ring, or only in one of the rings. Where a heterocycle group contains more than one ring, not all rings must contain a heteroatom. A heteroatom may beS, O or N, and is suitably O or N. Suitably a heterocycle group contains 5-10 ring members.A heterocycle may contain one heteroatom selected from N, S and O, for example N and O, especially N. In other examples a heterocycle may contain two heteroatoms selected from N, S and O. In further examples a heterocycle may contain three heteroatoms selected from N, S and O, for example N and O. In some examples the heterocycle is monocyclic, such asa 5- or 6- membered heterocycle ring. Examples of heterocycles include morpholinyl,tetrahydrofuran, and tetrahydropyran.As used herein, the term C5-11spirocarbocyclyl means a cyclic ring system containing 5 to 11carbon atoms, wherein R4 and R5 are part of the sprirocarbocyclyl with the carbon that theyare attached to. An example of a C5-11spirocarbocyclyl is spiropentane.The term “aryl” as used herein in relation to substances of formula (I), (II), and (III), whetheralone or forming part of a larger group e.g. C1-4alkylene(aryl), OC1-4alkylene(aryl) or C1-4alkyleneO(aryl), refers to a phenyl ring. Optionally, the aryl may be substituted as defined herein. The term ‘aryl’ as used herein in relation to substances of formula (V), (VA), (VI), or (VIB), refers to a mono (i.e. phenyl) or polycyclic ring system (e.g. comprising one or two, such as one additional ring) containing at least one phenyl ring, suitably an aryl group contains 6-10 ring members. Additional rings in a polycylic ring system may be saturated (e.g forming indane or tetralin) or partially unsaturated (e.g. forming indene) or fully unsaturated (e.g. forming naphthalene) hydrocarbon rings, or additional rings may be saturated or partially unsaturated heterocycles (e.g. forming chromane). Suitably aryl refers to a mono (i.e. phenyl) or a bicyclic ring system containing at least one phenyl ring (and no heteroaryl rings). The term ‘heteroaryl’ as used herein refers to mono or polycyclic ring system (e.g bicyclic) with at least one ring having aromatic character and containing at least one heteroatomselected from N, O and S, for example N. Suitably a heteroaryl group contains 5-10 ringmembers. Where a heteroaryl group contains more than one ring, not all rings must containa heteroatom, and not all rings must be aromatic in character. In some examples heteroarylis monocyclic, such as a 5- or 6- membered heteroaryl ring (e.g. containing one or twoheteroatom selected from N, S and O). In other examples heteroaryl is bicyclic, such as a5,5-, 5,6- or 6,6- bicyclic system (e.g. containing one, two or three heteroatoms selectedfrom N, S and O). A heteroaryl may contain one heteroatom selected from N, S and O, forexample N and O, especially N. In other examples a heteroaryl may contain two heteroatoms selected from N, S and O. In further examples a heteroaryl may contain three heteroatoms selected from N, S and O, for example N and O. Examples of 6-membered heteroaryls include one nitrogen atom (pyridinyl), two nitrogen atoms (pyridazinyl, pyrimidinyl or pyrazinyl) and three nitrogen atoms (triazinyl). Further examples of heteroaryl include triazolyl, indolyl, indazolyl, benzofuranyl, benzimidazolyl, benzoxazolinyl, quinolinyl, isoquinolinyl and quinazolinyl. The term “haloalkyl” as used herein, such as in C1-4haloalkyl, whether alone or forming part of a larger group such as OC1-4haloalkyl, is a straight or branched alkyl group containing the specified number of carbon atoms, substituted by one or more halo atoms, for example fluoromethyl (CH2F), di-fluoromethyl (CHF2), tri-fluoromethyl (CF3), 1-fluoroethyl (CH2FCH2) and 2-fluoroethyl (CH2CH2F). The term “haloalkoxy” as used herein, such as in C1-4haloalkoxy, refers to an haloalkyl group (e.g. a C1-4haloalkyl group) as defined above, singularly bonded to an oxygen atom, for example, trifluoromethoxy. The term “fluoroalkyl” as used herein, such as in C1-3fluoroalkyl, is a straight or branched alkyl group containing the specified number of carbon atoms, substituted by one or more fluoro atoms, for example fluoromethyl (CH2F), di-fluoromethyl (CHF2), tri-fluoromethyl (CF3), 1-fluoroethyl (CH2FCH2) and 2-fluoroethyl (CH2CH2F). The term “fluoroalkoxy” as used herein, such as in C1-3fluoroalkoxy, is a linear or branched, saturated, monovalent C1-3alkoxy group, as defined above, in which one or more of the hydrogen atoms is replaced, identically or differently, with a halogen atom for example -OCF3, -OCHF2, -OCH2F, -OCF2CF3and -OCH2CF3. The term ‘halo’ or ‘halogen’ as used herein, refers to fluorine, chlorine, bromine or iodine. Particular examples of halo are bromine, fluorine and chlorine, especially fluorine. Where substituents are indicated as being optionally substituted the optional substituent may be attached to an available carbon atom, which means a carbon atom which is attached to a hydrogen atom i.e. a C-H group or the optional substituent may be attached to an available nitrogen atom, which means a nitrogen atom which is attached to a hydrogen atom i.e. a N-H group. The optional substituent replaces the hydrogen atom attached to the carbon atom or the hydrogen atom attached to the nitrogen atom.In one aspect, the present invention provides a substance of formula (I): wherein: R1ais H or methyl; R1bis H or F; A is group (Aa), (Ab), (Ac) or (Ad): wherein group (Aa) is: wherein: R2 is H, C1-4alkyl, C1-4alkylene(aryl), C1-4alkylene(OH), C1-4alkylene(C3-6cycloalkyl), C1- 4alkylene(4-7 membered heterocycloalkyl), C1-4alkoxy, OC1-4alkylene(aryl), C1-4alkyleneOC1- 4alkyl, C1-4alkyleneOC3-6cycloalkyl, C1-4alkyleneO(4-7 membered heterocycloalkyl), C1- 4alkyleneO(aryl), C3-6alkynyl or C1-4alkenylO(C3-6alkynyl); wherein said aryl, heterocycloalkyl and cycloalkyl are optionally substituted by 1, 2 or 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR2aR2b, SO2R2c and NHSO2R2c; R2a is selected from H and C1-4alkyl; R2b is selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R2c is selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; each R3 is independently halo, methyl, ethyl or n-propyl; m is 0, 1, 2, 3 or 4; wherein group (Ab) is: wherein: R4is H, C1-4alkyl or C1-4alkylene(aryl); wherein said aryl is optionally substituted by 1, 2 or 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR4aR4b, SO2R4cand NHSO2R4c; R4ais selected from H and C1-4alkyl; R4bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R4cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R5is H or C1-4alkyl; each R6is independently C1-4alkyl or halo; n is 0, 1, 2 or 3; wherein group (Ac) is: wherein: R7 is C1-4alkyl, C1-4alkylene(OH) or C1-4alkyleneOC1-4alkyl; o is 1 or 2; wherein group (Ad) is: wherein: X is a bond, O or CH2; each R8 is independently halo, C1-4alkyl, C1-4alkoxy, OC1-4haloalkyl, OC1-4alkylene(C3- 6cycloalkyl), OC1-4alkylene(4-7 membered heterocycloalkyl) or OH; wherein said heterocycloalkyl and cycloalkyl are optionally substituted by 1, 2 or 3 substituents independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR8aR8b, SO2R8cand NHSO2R8c; R8ais selected from H and C1-4alkyl; R8bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R8cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; each R9is independently halo or C1-4alkyl; p is 0, 1 or 2; q is 0, 1, 2, 3 or 4; wherein B is group (Ba), (Bb) or (Bc): wherein group (Ba) is: wherein: Y is C(R11)(R12), N(R13), O or S; each R10is independently halo or C1-4alkyl; r is 0, 1, 2 or 3; R11is H or C1-4alkyl; R12is H or C1-4alkyl; or R11and R12together with the carbon atom to which they are attached form a C3-6cycloalkyl; R13is H, C1-4alkyl or C3-6cycloalkyl; wherein said cycloalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR13aR13b, SO2R13cand NHSO2R13c; R13ais selected from H and C1-4alkyl; R13bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R13cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; wherein group (Bb) is: wherein: each R14 is independently halo or C1-4alkyl; s is 0, 1, 2 or 3; wherein group (Bc) is: wherein: R15is C1-4alkyl, C1-4alkoxy, C3-6cycloalkyl, C1-4haloalkyl, halo or CN; wherein said cycloalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR15aR15b, SO2R15cand NHSO2R15c; R15ais selected from H and C1-4alkyl; R15bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R15cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R16is H, halo or C1-4alkyl; and D, E and F are each independently C(R16); or one of D, E and F is N, and the two remaining D, E and F groups are independently C(R16); or a pharmaceutically acceptable salt and / or solvate thereof, for use in the prevention or treatment of a disease, disorder, or condition which is an Other NLRX1-Related Disease, Disorder or Condition. Suitable substances of formula (I), and compositions containing them, and processes forpreparing them, are further described in WO2022 / 049376, which is herein incorporated byreference in its entirety. It will be understood that suitable and / or preferred substances of formula (I) may include any of the substances (generic or specific) disclosed in WO2022 / 049376.Suitably, the present invention provides a substance of formula (I), for use according to thepresent invention, wherein A is group (Aa): Suitably, when A of the substance of formula (I), for use according to the present invention,is group (Aa), R2 is C1-4alkyl, C1-4alkylene(aryl), C1-4alkylene(OH), C1-4alkyleneOC1-4alkyl, C1-4alkyleneOC3-6cycloalkyl, C1-4alkyleneO(aryl), C1-4alkylene(4-7 membered heterocycloalkyl), C1-4alkyleneO(4-7 membered heterocycloalkyl) or C1-4alkyleneO(C3-6alkynyl); wherein said aryl, heterocycloalkyl and cycloalkyl may be optionally substituted by up to 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo and CN. In one aspect of the invention, the aryl is unsubstituted. In another aspect of the invention, the aryl is substituted by 1, 2 or 3 substituents independently selected from methyl, chloro and fluoro. Alternatively, in one aspect of the invention, the heterocycloalkyl is unsubstituted. In another aspect of the invention, the heterocycloalkyl is substituted by 1, 2 or 3 substituents independently selected from CH2CH2F and fluoro.Suitably, when A of the substance of formula (I), for use according to the present invention,is group (Aa), each R3 is independently fluoro or methyl. Moreover, when A of the substanceof formula (I), for use according to the present invention, is group (Aa), m is suitably 1 or 2.For example, suitably m is 1 and R3 is in the 3-position. Alternatively, suitably m is 1 and R3is in the 6-position. In another aspect, suitably m is 2, one R3is in the 3-position, and the other R3is in the 6-position.Suitably, the present invention provides a substance of formula (I), for use according to thepresent invention, wherein A is group (Ab): Suitably, when A of the substance of formula (I), for use according to the present invention,is group (Ab), R4 is H, methyl or benzyl. Moreover, when A of the substance of formula (I),for use according to the present invention, is group (Ab), R5 is suitably H. Furthermore, whenA of the substance of formula (I), for use according to the present invention, is group (Ab),suitably each R6 is independently fluoro or methyl. In one aspect of the invention, when A ofthe substance of formula (I), for use according to the present invention, is group (Ab), n is 1.Suitably, the present invention provides a substance of formula (I), for use according to thepresent invention, wherein A is group (Ac): Suitably, when A of the substance of formula (I), for use according to the present invention,is group (Ac), R7 is methyl, CH2OH or CH2OMe. Moreover, when A of the substance offormula (I), for use according to the present invention, is group (Ac), o is suitably 2.Suitably, the present invention provides a substance of formula (I), for use according to thepresent invention, wherein A is group (Ad): Suitably, when A of the substance of formula (I), for use according to the present invention,is group (Ad), X is a bond or O. Moreover, when A of the substance of formula (I), for useaccording to the present invention, is group (Ad), suitably each R8is independently OCH2- cyclopropyl, OCH2-oxetanyl, OCH2CH2F, methyl, OMe, oEt or fluoro, for example methyl, OMe or fluoro, in particular each R8is independently OCH2-cyclopropyl, OCH2-oxetanyl,OCH2CH2F or oEt, for example each R8 is independently OCH2CH2F, OMe or oEt, especiallyOMe. Furthermore, when A of the substance of formula (I), for use according to the presentinvention, is group (Ad), suitably p is 0 or 1. Suitably, when A of the substance of formula (I), for use according to the present invention,is group (Ad), each R9 is independently fluoro. Moreover, when A of the substance offormula (I), for use according to the present invention, is group (Ad), suitably q is 1 or 2.Suitably, the present invention provides a substance of formula (I), for use according to thepresent invention, wherein group B is (Ba): Suitably, when B of the substance of formula (I), for use according to the present invention,is group (Ba), Y is C(R11)(R12) or N(R13), wherein, suitably, (i) R11 is H or methyl and R12 is H, or (ii) R11 and R12 are both H, or (iii) R11 and R12 together to the carbon atom to which they are attached form a cyclopropyl ring, and wherein R13is suitably C1-4alkyl, such as methyl, ethyl, propyl or butyl, especially methyl; or C3-6cycloalkyl, such as cyclopropyl. Alternatively,suitably, when B of the substance of formula (I), for use according to the present invention, isgroup (Ba), Y is O or S.Suitably, when B of the substance of formula (I), for use according to the present invention,is group (Ba), each R10is independently fluoro, chloro or methyl. Moreover, when B of thesubstance of formula (I), for use according to the present invention, is group (Ba), r issuitably 0 or 1.Suitably, the present invention provides a substance of formula (I), for use according to thepresent invention, wherein group B is (Bb):Suitably, when B of the substance of formula (I), for use according to the present invention,is group (Bb), each R14 is independently fluoro or methyl. Moreover, when B of thesubstance of formula (I), for use according to the present invention, is group (Bb), s issuitably 0 or 1.Suitably, the present invention provides a substance of formula (I), for use according to thepresent invention, wherein group B is (Bc): Suitably, when B of the substance of formula (I), for use according to the present invention,is group (Bc), R15 is methyl, ethyl, cyclopropyl, CF3, CN, OMe, chloro or fluoro e.g. methyl,ethyl, cyclopropyl, CF3 or CN, in particular R15 is OMe, chloro or fluoro or R15 is methyl, CN,chloro or fluoro.Suitably, when B of the substance of formula (I), for use according to the present invention,is group (Bc), D, E and F are C(R16), or; D is N, and E and F are C(R16) or; E is N, and D andF are C(R16) or; F is N, and D and E are C(R16); wherein each R16 is independently H, fluoro,chloro or methyl.For example, in one aspect, the present invention provides a substance of formula (I), foruse according to the present invention, wherein the substance of formula (I) is selected fromthe group consisting of: (E)-3-(1H-benzo[d][1,2,3]triazol-6-yl)-N-(3-fluoro-2-methylphenyl)acrylamide; (E)-N-(3-fluoro-2-methylphenyl)-3-(2-oxo-2,3-dihydrobenzo[d]thiazol-5-yl)acrylamide; (E)-3-(3,3-dimethyl-2-oxoindolin-6-yl)-N-(3-fluoro-2-methylphenyl)acrylamide; (E)-N-(3-fluoro-2-methylphenyl)-3-(2'-oxospiro[cyclopropane-1,3'-indolin]-6'-yl)acrylamide; (E)-N-(3-fluoro-2-methylphenyl)-3-(7-fluoro-2-oxoindolin-6-yl)acrylamide; (E)-N-(3-fluoro-2-methylphenyl)-3-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)acrylamide; (E)-N-(3-fluoro-2-methylphenyl)-3-(1-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl) acrylamide; (E)-N-(3-fluoro-2-methylphenyl)-3-(3-methyl-2-oxoindolin-6-yl)acrylamide; (E)-N-(3-chloro-2-methylphenyl)-3-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)acrylamide; (E)-N-(3-fluoro-2-methylphenyl)-3-(2-oxoindolin-6-yl)acrylamide; (E)-N-(2,3-dihydro-1H-inden-1-yl)-3-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)acrylamide; (E)-3-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)-N-(o-tolyl)acrylamide; (E)-N-(2-isopropylphenyl)-3-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)acrylamide; (E)-N-(2-isopropyl-6-methylphenyl)-3-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)acrylamide; (E)-N-(5-chloro-2-isopropylphenyl)-3-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)acrylamide; (E)-N-(4,5-difluoro-2-methylphenyl)-3-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)acrylamide; (E)-N-(5-fluoro-2-methylphenyl)-3-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)acrylamide; (E)-N-(3-fluoro-2-methylphenyl)-3-(4-fluoro-2-oxoindolin-6-yl)acrylamide; (E)-N-(2,6-dimethylphenyl)-3-(2-oxoindolin-6-yl)acrylamide; (E)-N-(3-fluoro-2,6-dimethylphenyl)-3-(2-oxoindolin-6-yl)acrylamide; (E)-N-(2-methyl-2,3-dihydro-1H-inden-1-yl)-3-(2-oxoindolin-6-yl)acrylamide; (E)-3-(1-ethyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-N-(3-fluoro-2-methylphenyl) acrylamide; (E)-3-(1-cyclopropyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-N-(3-fluoro-2- methylphenyl) acrylamide; (E)-N-(2,3-dihydro-1H-inden-1-yl)-3-(1-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl) acrylamide; (E)-N-(2,3-dihydro-1H-inden-1-yl)-3-(3-methyl-1H-indazol-6-yl)acrylamide; (E)-3-(3-cyano-1H-indazol-6-yl)-N-(2,3-dihydro-1H-inden-1-yl)acrylamide; (E)-N-(2,3-dihydro-1H-inden-1-yl)-3-(5-fluoro-1H-benzo[d][1,2,3]triazol-6-yl)acrylamide; (E)-N-(2,3-dihydro-1H-inden-1-yl)-3-(3-(trifluoromethyl)-1H-indazol-6-yl)acrylamide; (E)-N-(2,6-dimethylphenyl)-3-(1-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5- yl)acrylamide; (E)-N-(3-fluoro-2,6-dimethylphenyl)-3-(1-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5- yl)acrylamide; (E)-N-(2,6-dimethylphenyl)-3-(3-methyl-1H-indazol-6-yl)acrylamide; (E)-N-(2,3-dihydro-1H-inden-1-yl)-3-(3-ethyl-1H-indazol-6-yl)acrylamide; (E)-3-(3-cyclopropyl-1H-indazol-6-yl)-N-(2,3-dihydro-1H-inden-1-yl)acrylamide; (E)-N-(2,3-dihydro-1H-inden-1-yl)-3-(4-fluoro-3-methyl-1H-indazol-6-yl)acrylamide; (E)-N-(3,5-difluoro-2,6-dimethylphenyl)-3-(2-oxoindolin-6-yl)acrylamide; (E)-N-(3,4-difluoro-2,6-dimethylphenyl)-3-(2-oxoindolin-6-yl) acrylamide; (E)-N-(3-fluoro-2-methylphenyl)-3-(3-methyl-1H-indazol-6-yl)acrylamide; (E)-3-(3-methyl-1H-indazol-6-yl)-N-(2-methyl-2,3-dihydro-1H-inden-1-yl)acrylamide; (E)-3-(3-methyl-1H-indazol-6-yl)-N-(1-methyl-1H-indazol-7-yl)acrylamide; (E)-N-(5-fluoro-2,3-dihydro-1H-inden-1-yl)-3-(3-methyl-1H-indazol-6-yl)acrylamide; (E)-N-(4-fluoro-3-methylphenyl)-3-(3-methyl-1H-indazol-6-yl)acrylamide; (E)-N-(3-fluoro-4-methylphenyl)-3-(3-methyl-1H-indazol-6-yl)acrylamide; Racemic-(E)-3-(3-methyl-1H-indazol-6-yl)-N-((1R,2R)-2-methylcyclohexyl)acrylamide; (E)-3-(3-cyano-1H-indazol-6-yl)-N-(2-methyl-2,3-dihydro-1H-inden-1-yl)acrylamide; (E)-N-(2-methyl-2,3-dihydro-1H-inden-1-yl)-3-(1-methyl-2-oxo-2,3-dihydro-1H- benzo[d]imidazol-5-yl)acrylamide; (E)-N-(2-methyl-2,3-dihydro-1H-inden-1-yl)-3-(2-oxo-2,3-dihydrobenzo[d]oxazol-5- yl)acrylamide; (Z)-2-fluoro-N-(3-fluoro-2-methylphenyl)-3-(2-oxoindolin-6-yl)acrylamide; (E)-N-(3-chloro-2-methylphenyl)-N-methyl-3-(2-oxo-2,3-dihydrobenzo[d]oxazol-5- yl)acrylamide; (E)-N-(2-methylcyclopentyl)-3-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)acrylamide; (E)-N-(3-fluoro-2-(methoxymethyl)phenyl)-3-(3-methyl-1H-indazol-6-yl)acrylamide; (E)-3-(3-cyano-1H-indazol-6-yl)-N-(3-fluoro-2-methylphenyl)acrylamide; (E)-3-(3-methyl-1H-indazol-6-yl)-N-(3-methylchroman-4-yl)acrylamide; (E)-N-(2-methyl-1,2,3,4-tetrahydronaphthalen-1-yl)-3-(3-methyl-1H-indazol-6-yl)acrylamide; (E)-N-((1S,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl)-3-(3-methyl-1H-indazol-6- yl)acrylamide; (R,E)-N-(2,3-dihydro-1H-inden-1-yl)-3-(3-methyl-1H-indazol-6-yl)acrylamide; (E)-N-(chroman-4-yl)-3-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)acrylamide; (E)-3-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)-N-(1,2,3,4-tetrahydronaphthalen-1- yl)acrylamide; (E)-N-(2-methyl-1,2,3,4-tetrahydronaphthalen-1-yl)-3-(2-oxoindolin-6-yl)acrylamide; (E)-N-(2,3-dihydro-1H-inden-1-yl)-3-(2-oxoindolin-6-yl)acrylamide; (E)-N-(3,5-difluoro-2-methylphenyl)-3-(2-oxoindolin-6-yl)acrylamide; (E)-N-(2,3-dihydro-1H-inden-1-yl)-3-(7-fluoro-1H-benzo[d][1,2,3]triazol-6-yl)acrylamide; (E)-N-(2,3-dihydro-1H-inden-1-yl)-3-(4-fluoro-1H-benzo[d][1,2,3]triazol-6-yl)acrylamide; (E)-N-(5-chloro-2-methylphenyl)-3-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)acrylamide; (E)-N-(2-methylcyclohexyl)-3-(2-oxoindolin-6-yl)acrylamide; (E)-3-(3-methyl-1H-indazol-6-yl)-N-(-3-methylchroman-4-yl)acrylamide; (E)-3-(3-methyl-1H-indazol-6-yl)-N-((3R,4S)-3-methylchroman-4-yl)acrylamide; (E)-3-(3-methyl-1H-indazol-6-yl)-N-((3S,4R)-3-methylchroman-4-yl)acrylamide; (E)-3-(3-methyl-1H-indazol-6-yl)-N-((3R,4R)-3-methylchroman-4-yl)acrylamide; (E)-3-(3-methyl-1H-indazol-6-yl)-N-((3S,4S)-3-methylchroman-4-yl)acrylamide; (E)-3-(3-methyl-1H-indazol-6-yl)-N-((1S,2S)-2-(oxetan-3-ylmethoxy)-2,3-dihydro-1H-inden-1- yl)acrylamide; (E)-N-((1S,2S)-2-(cyclopropylmethoxy)-2,3-dihydro-1H-inden-1-yl)-3-(3-methyl-1H-indazol-6- yl)acrylamide; (E)-N-((1S,2S)-2-(2-fluoroethoxy)-2,3-dihydro-1H-inden-1-yl)-3-(3-methyl-1H-indazol-6- yl)acrylamide; (E)-N-((1S,2S)-2-ethoxy-2,3-dihydro-1H-inden-1-yl)-3-(3-methyl-1H-indazol-6-yl)acrylamide; (E)-3-(3-cyclopropyl-1H-indazol-6-yl)-N-((1S,2S)-2-methoxy-2,3-dihydro-1H-inden-1- yl)acrylamide; (E)-3-(3-methoxy-1H-indazol-6-yl)-N-((1S,2S)-2-methoxy-2,3-dihydro-1H-inden-1- yl)acrylamide; (E)-3-(3-chloro-1H-indazol-6-yl)-N-((1S,2S)-2-methoxy-2,3-dihydro-1H-inden-1- yl)acrylamide; (E)-3-(3-fluoro-1H-indazol-6-yl)-N-((1S,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl)acrylamide; and (E)-3-(3-cyano-1H-indazol-6-yl)-N-((1S,2S)-2-methoxy-2,3-dihydro-1H-inden-1- yl)acrylamide; or a pharmaceutically acceptable salt and / or solvate of any one thereof.In another aspect, the present invention provides a substance of formula (II): wherein: R1ais H or methyl; R1bis H or fluoro; A is group (Aa), (Ab), (Ac) or (Ad): wherein group (Aa) is: wherein: R2is H, C1-4alkyl, C1-4alkylene(aryl), C1-4alkylene(OH), C1-4alkylene(C3-6cycloalkyl), C1-4alkylene(4-7 membered heterocycloalkyl), C1-4alkoxy, OC1-4alkylene(aryl), C1-4alkyleneOC1-4alkyl, C1-4alkyleneOC3-6cycloalkyl, C1-4alkyleneO(4-7 membered heterocycloalkyl), C1-4alkyleneO(aryl), C3-6alkynyl and C1-4alkyleneO(C3-6alkynyl); wherein said aryl, heterocycloalkyl or cycloalkyl are optionally substituted by 1, 2 or 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR2aR2b, SO2R2cand NHSO2R2c; R2ais selected from H and C1-4alkyl; R2bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R2cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; each R3is independently halo, methyl, ethyl or n-propyl; m is 0, 1, 2, 3 or 4; wherein group (Ab) is: wherein: R4 is H, C1-4alkyl or C1-4alkylene(aryl); wherein said aryl is optionally substituted by 1, 2 or 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1- 4alkoxy, C1-4haloalkyl, halo, CN, OH, NR4aR4b, SO2R4c and NHSO2R4c; R4a is selected from H and C1-4alkyl; R4b is selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R4cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R5is H or C1-4alkyl; each R6is independently C1-4alkyl or halo; n is 0, 1, 2 or 3; wherein group (Ac) is: wherein: R7is C1-4alkyl, C1-4alkylene(OH) or C1-4alkyleneOC1-4alkyl; o is 1 or 2; wherein group (Ad) is: wherein: X is a bond, O or CH2; each R8 is independently halo, C1-4alkyl, C1-4alkoxy OC1-4haloalkyl, OC1-4alkylene(C3- 6cycloalkyl), OC1-4alkylene(4-7 membered heterocycloalkyl) or OH; wherein said heterocycloalkyl and cycloalkyl are optionally substituted by 1, 2 or 3 substituents independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR8aR8b, SO2R8c and NHSO2R8c; R8a is selected from H and C1-4alkyl; R8b is selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R8c is selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; each R9 is independently halo or C1-4alkyl; p is 0, 1 or 2; q is 0, 1, 2, 3 or 4; wherein B is: wherein: R10is H, halo or C1-4alkyl; D, E and F are each independently C(R10); or one of D, E and F is N and the two remaining D, E and F groups are independently C(R10); or a pharmaceutically acceptable salt and / or solvate thereof, for use in the prevention or treatment of a disease, disorder, or condition which is an Other NLRX1-Related Disease, Disorder or Condition. Suitable substances of formula (II), and compositions containing them, and processes forpreparing them, are further described in WO2022 / 049377, which is herein incorporated by reference in its entirety. It will be understood that suitable and / or preferred substances of formula (II) may include any of the substances (generic or specific) disclosed in WO2022 / 049377.Suitably, the present invention provides a substance of formula (II), for use according to thepresent invention, wherein A is group (Aa): Suitably, when A of the substance of formula (II), for use according to the present invention,is group (Aa), R2 is C1-4alkyl, C1-4alkylene(aryl), C1-4alkylene(OH), C1-4alkyleneOC1-4alkyl, C1- 4alkyleneOC3-6cycloalkyl, C1-4alkyleneO(aryl), C1-4alkylene(4-7 membered heterocycloalkyl), C1-4alkyleneO(4-7 membered heterocycloalkyl) and C1-4alkyleneO(C3-6alkynyl); wherein said aryl, heterocycloalkyl or cycloalkyl may be optionally substituted by up to 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl; C1-4alkoxy, C1-4haloalkyl, halo and CN. In one aspect of the invention, the aryl is unsubstituted. In another aspect of the invention, the aryl is substituted by 1, 2 or 3 substituents independently selected from methyl, chloroand fluoro. In one aspect of the invention, the heterocycloalkyl is unsubstituted. In anotheraspect of the invention, the heterocycloalkyl is substituted by 1, 2 or 3 substituents independently selected from CH2CH2F and fluoro.Suitably, when A of the substance of formula (II), for use according to the present invention,is group (Aa), each R3is independently fluoro or methyl. Moreover, when A of the substance of formula (II), for use according to the present invention, is group (Aa), m is suitable 1 or 2.For example, suitably, m is 1 and R3 is in the 3-position. Alternatively, suitably, m is 1 and R3is in the 6-position. In another aspect, suitably, m is 2, one R3 is in the 3-position, and the other R3 is in the 6-position.Suitably, the present invention provides a substance of formula (II), for use according to thepresent invention, wherein A is group (Ab):Suitably, when A of the substance of formula (II), for use according to the present invention,is group (Ab), R4 is H, methyl or benzyl. Moreover, when A of the substance of formula (II),for use according to the present invention, is group (Ab), R5 is suitably H. Furthermore, whenA of the substance of formula (II), for use according to the present invention, is group (Ab),suitably, each R6 is independently fluoro or methyl. In one aspect of the invention, when A ofthe substance of formula (II), for use according to the present invention, is group (Ab), n issuitably 0.Suitably, the present invention provides a substance of formula (II), for use according to thepresent invention, wherein A is group (Ac): Suitably, when A of the substance of formula (II), for use according to the present invention,is group (Ac), R7 is methyl, CH2OH or CH2OMe. Moreover, when A of the substance offormula (II), for use according to the present invention, is group (Ac), o is suitably 2.Suitably, the present invention provides a substance of formula (II), for use according to thepresent invention, wherein A is group (Ad): Suitably, when A of the substance of formula (II), for use according to the present invention,is group (Ad), X is a bond or O. Moreover, when A of the substance of formula (II), for useaccording to the present invention, is group (Ad), suitably, each R8 is independently methyl,OMe or fluoro. Furthermore, when A of the substance of formula (II), for use according to thepresent invention, is group (Ad), p is suitably 0 or 1.Suitably, when A of the substance of formula (II), for use according to the present invention,is group (Ad), each R9 is independently fluoro. Moreover, when A of the substance offormula (II), for use according to the present invention, is group (Ad), q is suitably 1 or 2.In relation to the group B of the substance of formula (II), for use according to the presentinvention, suitably D, E and F are C(R10) or; D is N, and E and F are C(R10) or; E is N, and Dand F are C(R10) or; F is N, and D and E are C(R10); wherein each R10 is independently H,fluoro, chloro or methyl.For example, in one aspect, the present invention provides a substance of formula (II), foruse according to the present invention, wherein the substance of formula (II) is selected fromthe group consisting of: (E)-N-(3-fluoro-2-methylphenyl)-3-(7-methyl-1H-indazol-6-yl)acrylamide; (E)-N-(2,3-dihydro-1H-inden-1-yl)-3-(1H-indazol-6-yl)acrylamide; (R,E)-N-(2,3-dihydro-1H-inden-1-yl)-3-(1H-indazol-6-yl)acrylamide; (E)-3-(1H-indazol-6-yl)-N-((1R,2R)-2-methylcyclohexyl) acrylamide (racemic mixture); (E)-3-(1H-indazol-6-yl)-N-((1R,2R)-2-methylcyclohexyl) acrylamide (enantiomer 1); (E)-3-(1H-indazol-6-yl)-N-((1R,2R)-2-methylcyclohexyl) acrylamide (enantiomer 2); (E)-N-(7-fluoro-2,3-dihydro-1H-inden-1-yl)-3-(1H-indazol-6-yl)acrylamide; (E)-N-(6-fluoro-2,3-dihydro-1H-inden-1-yl)-3-(1H-indazol-6-yl)acrylamide; (E)-N-(5-fluoro-2,3-dihydro-1H-inden-1-yl)-3-(1H-indazol-6-yl)acrylamide; (E)-N-(4-fluoro-2,3-dihydro-1H-inden-1-yl)-3-(1H-indazol-6-yl)acrylamide; (E)-N-(2,3-dihydro-1H-inden-1-yl)-3-(7-fluoro-1H-indazol-6-yl)acrylamide; (E)-N-(2,3-dihydro-1H-inden-1-yl)-3-(5-fluoro-1H-indazol-6-yl)acrylamide; (E)-N-(2,3-dihydro-1H-inden-1-yl)-3-(4-fluoro-1H-indazol-6-yl)acrylamide; (E)-3-(5-chloro-1H-indazol-6-yl)-N-(2,3-dihydro-1H-inden-1-yl)acrylamide; (E)-3-(4-chloro-1H-indazol-6-yl)-N-(2,3-dihydro-1H-inden-1-yl)acrylamide; (E)-3-(1H-indazol-6-yl)-N-(2-methyl-2,3-dihydro-1H-inden-1-yl)acrylamide (mixture of stereoisomers); (E)-3-(1H-indazol-6-yl)-N-(2-methyl-2,3-dihydro-1H-inden-1-yl)acrylamide (stereoisomer 1); (E)-3-(1H-indazol-6-yl)-N-(2-methyl-2,3-dihydro-1H-inden-1-yl)acrylamide (stereoisomer 2); (E)-3-(1H-indazol-6-yl)-N-(2-methyl-2,3-dihydro-1H-inden-1-yl)acrylamide (stereoisomer 3); (E)-3-(1H-indazol-6-yl)-N-(2-methyl-2,3-dihydro-1H-inden-1-yl)acrylamide (stereoisomer 4); (E)-3-(1H-indazol-6-yl)-N-(3-methylchroman-4-yl)acrylamide (mixture of stereoisomers); (E)-3-(1H-indazol-6-yl)-N-(3-methylchroman-4-yl)acrylamide (stereoisomer 1); (E)-3-(1H-indazol-6-yl)-N-(3-methylchroman-4-yl)acrylamide (stereoisomer 2); (E)-3-(1H-indazol-6-yl)-N-(3-methylchroman-4-yl)acrylamide (stereoisomer 3); (E)-3-(1H-indazol-6-yl)-N-(3-methylchroman-4-yl)acrylamide (stereoisomer 4); (E)-N-(2-(benzyloxy)phenyl)-3-(1H-indazol-6-yl)acrylamide; (E)-3-(1H-indazol-6-yl)-N-(2-(phenoxymethyl)phenyl)acrylamide; (E)-N-(2-(cyclobutoxymethyl)phenyl)-3-(1H-indazol-6-yl)acrylamide; (E)-N-(1-benzyl-1H-indazol-7-yl)-3-(1H-indazol-6-yl)acrylamide; (E)-3-(1H-indazol-6-yl)-N-(1-methyl-1H-indazol-7-yl)acrylamide; (E)-3-(1H-indazol-6-yl)-N-(m-tolyl)acrylamide; (E)-N-(3-chlorophenyl)-3-(1H-indazol-6-yl)acrylamide; (E)-N-(3-fluorophenyl)-3-(1H-indazol-6-yl)acrylamide; (E)-N-(2,6-dimethylphenyl)-3-(1H-indazol-6-yl)acrylamide; (E)-N-((1R,3R)-3-fluoro-2,3-dihydro-1H-inden-1-yl)-3-(1H-indazol-6-yl)acrylamide (mixture of stereoisomers); (E)-N-((1R,3R)-3-fluoro-2,3-dihydro-1H-inden-1-yl)-3-(1H-indazol-6-yl)acrylamide (stereoisomer 1); (E)-N-((1R,3S)-3-fluoro-2,3-dihydro-1H-inden-1-yl)-3-(1H-indazol-6-yl)acrylamide (stereoisomer 2); (E)-N-(2-(hydroxymethyl)phenyl)-3-(1H-indazol-6-yl)acrylamide; (E)-N-(3-fluoro-2,6-dimethylphenyl)-3-(1H-indazol-6-yl)acrylamide; (E)-3-(1H-indazol-6-yl)-N-(2-(methoxymethyl)phenyl)acrylamide; (E)-N-(2-(((1-(2-fluoroethyl)azetidin-3-yl)oxy)methyl)phenyl)-3-(1H-indazol-6-yl)acrylamide hydrochloride; (E)-N-(2-((3-fluoroazetidin-1-yl)methyl)phenyl)-3-(1H-indazol-6-yl)acrylamide; (E)-N-(2-(2-(3-fluoroazetidin-1-yl)ethyl)phenyl)-3-(1H-indazol-6-yl)acrylamide; (E)-N-(2-fluoro-6-methylphenyl)-3-(1H-indazol-6-yl)acrylamide; (E)-N-(3-fluoro-2-methylphenyl)-3-(1H-pyrazolo[4,3-b]pyridin-6-yl)acrylamide; (E)-N-(2,3-dihydro-1H-inden-1-yl)-3-(1H-pyrazolo[4,3-c]pyridin-6-yl)acrylamide; (E)-N-(2,3-dihydro-1H-inden-1-yl)-3-(1H-pyrazolo[3,4-b]pyridin-6-yl)acrylamide; (E)-3-(1H-indazol-6-yl)-N-((1S,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl)acrylamide; (E)-3-(1H-indazol-6-yl)-N-(7-methyl-2,3-dihydro-1H-inden-1-yl)acrylamide; (E)-3-(1H-indazol-6-yl)-N-(3-methyl-2,3-dihydro-1H-inden-1-yl)acrylamide; and (E)-3-(1H-indazol-6-yl)-N-(2-((prop-2-yn-1-yloxy)methyl)phenyl)acrylamide; or a pharmaceutically acceptable salt and / or solvate of any one thereof.In another aspect, the present invention provides a substance of formula (III): wherein: R1a is H or methyl; R1b is H or F; A is group (Aa), (Ab), (Ac), (Ad) or (Ae): wherein group (Aa) is: wherein: R2is H, halo, C1-4alkyl, C1-4haloalkyl, C1-4alkylene(aryl), C1-4alkylene(OH), C1-4alkylene(C3-6cycloalkyl), C1-4alkylene(4-10 membered heterocycloalkyl), 4-10 membered heterocycloalkyl, C1-4alkoxy, OC1-4alkylene(aryl), C1-4alkyleneOC1-4alkyl, C1-4alkyleneOC3-6cycloalkyl, C1-4alkyleneO(4-10 membered heterocycloalkyl), C1- 4alkyleneO(aryl), C3-6alkynyl, C1-4alkenylO(C3-6alkynyl), C1-4alkylene(CO2H); OC1-4alkylene(CO2H), C1-4alkyleneOC1-4alkylene(CO2H), N(R2aa)C1-4alkylene(CO2H), C1-4alkylene(NR2abR2ac), OC1-4alkylene(NR2abR2ac) or N(R2aa)C1-4alkylene(NR2abR2ac); wherein said aryl, heterocycloalkyl and cycloalkyl are optionally substituted by 1, 2 or 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR2aR2b, SO2R2cand NHSO2R2c; R2ais selected from H and C1-4alkyl; R2bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R2cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; each R2aa is independently selected from H and C1-4alkyl; each R2ab is independently selected from H and C1-4alkyl; each R2ac is independently selected from H and C1-4alkyl; or R2ab and R2ac together with the nitrogen atom to which they are attached form a 4-10 membered heterocycloalkyl; R2xis H, halo, C1-4alkyl, C1-4haloalkyl or C1-4alkoxy; each R3is independently halo, C1-4alkyl, C1-4haloalkyl or C1-4alkoxy; m is 0, 1,2 or 3; or; R2xis C1-4alkylene(4-10 membered heterocycloalkyl), 4-10 membered heterocycloalkyl, C1-4alkyleneO(4-10 membered heterocycloalkyl), C1-4alkylene(CO2H), OC1-4alkylene(CO2H), C1-4alkyleneOC1-4alkylene(CO2H), N(R2xaa)C1-4alkylene(CO2H), C1-4alkylene(NR2xabR2xac), OC1-4alkylene(NR2xabR2xac) or N(R2xaa)C1-4alkylene(NR2xabR2xac); wherein said heterocycloalkyl is optionally substituted by 1, 2 or 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR2xaR2xb, SO2R2xcand NHSO2R2xc; R2xais selected from H and C1-4alkyl; R2xbis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R2xcis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; each R2xaa is independently selected from H and C1-4alkyl; each R2xab is independently selected from H and C1-4alkyl; each R2xac is independently selected from H and C1-4alkyl; or R2xab and R2xac together with the nitrogen atom to which they are attached form a 4-10 membered heterocycloalkyl; R2 is H, halo, C1-4alkyl, C1-4haloalkyl, C1-4alkoxy, C1-4alkyleneOC1-4alkyl, C1- 4alkyleneOC3-6cycloalkyl or C1-4alkyleneO(4-10 membered heterocycloalkyl); each R3 is independently halo, C1-4alkyl, C1-4haloalkyl or C1-4alkoxy; m is 0, 1, 2 or 3; wherein group (Ab) is: wherein: R4is H, C1-4alkyl or C1-4alkylene(aryl); wherein said aryl is optionally substituted by 1, 2 or 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR4aR4b, SO2R4cand NHSO2R4c; R4ais selected from H and C1-4alkyl; R4bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R4cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R5is H or C1-4alkyl; each R6is independently C1-4alkyl or halo; n is 0, 1, 2 or 3; wherein group (Ac) is: wherein: R7 is C1-4alkyl, C1-4alkylene(OH) or C1-4alkyleneOC1-4alkyl; o is 1 or 2; wherein group (Ad) is: wherein: X is a bond, O or CH2; each R8is independently halo, C1-4alkyl, C1-4alkoxy, OC1-4haloalkyl, OC1-4alkylene(C3-6cycloalkyl), OC1-4alkylene(4-10 membered heterocycloalkyl) or OH; wherein said heterocycloalkyl and cycloalkyl are optionally substituted by 1, 2 or 3 substituents independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR8aR8b, SO2R8cand NHSO2R8c; R8ais selected from H and C1-4alkyl; R8bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R8c is selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; each R9is independently halo or C1-4alkyl; p is 0, 1 or 2; q is 0, 1, 2, 3 or 4; wherein group (Ae) is: wherein: R17 is H, halo, C1-4alkyl, C1-4haloalkyl, C1-4alkylene(aryl), C1-4alkylene(OH), C1- 4alkylene(C3-6cycloalkyl), C1-4alkylene(4-10 membered heterocycloalkyl), 4-10 membered heterocycloalkyl, C1-4alkoxy, OC1-4alkylene(aryl), C1-4alkyleneOC1-4alkyl, C1-4alkyleneOC3-6cycloalkyl, C1-4alkyleneO(4-10 membered heterocycloalkyl), C1- 4alkyleneO(aryl), C3-6alkynyl, C1-4alkenylO(C3-6alkynyl), C1-4alkylene(CO2H), OC1- 4alkylene(CO2H), C1-4alkyleneOC1-4alkylene(CO2H), N(R17aa)C1-4alkylene(CO2H), C1- 4alkylene(NR17abR17ac), OC1-4alkylene(NR17abR17ac) or N(R17aa)C1- 4alkylene(NR17abR17ac); wherein said aryl, cycloalkyl or heterocycloalkyl is optionally substituted by 1, 2 or 3 substituents each independently selected from C1-4alkyl, C3- 6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR17aR17b, SO2R17c, NHSO2R17c; R17a is selected from H and C1-4alkyl; R17b is selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R17c is selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; each R17aa is independently selected from H and C1-4alkyl; each R17ab is independently selected from H and C1-4alkyl; each R17ac is independently selected from H and C1-4alkyl; or R17ab and R17ac together with the nitrogen atom to which they are attached form a 4-10 membered heterocycloalkyl; R18is H, halo, C1-4alkyl, C1-4haloalkyl, C1-4alkoxy, C1-4alkyleneOC1-4alkyl, C1-4alkyleneOC3-6cycloalkyl or C1-4alkyleneO(4-10 membered heterocycloalkyl); R20is H, halo, C1-4alkyl, C1-4haloalkyl or C1-4alkoxy; R21is H, halo, C1-4alkyl, C1-4haloalkyl or C1-4alkoxy; or; R17is H, halo, C1-4alkyl, C1-4haloalkyl, C1-4alkoxy, C1-4alkyleneOC1-4alkyl, C1-4alkyleneOC3-6cycloalkyl or C1-4alkyleneO(4-10 membered heterocycloalkyl); R18is C1-4haloalkyl, C1-4alkylene(aryl), C1-4alkylene(OH), C1-4alkylene(C3-6cycloalkyl), C1-4alkylene(4-10 membered heterocycloalkyl), 4-10 membered heterocycloalkyl, OC1-4alkylene(aryl), C1-4alkyleneOC1-4alkyl, C1-4alkyleneOC3-6cycloalkyl, C1-4alkyleneO(4-10 membered heterocycloalkyl), C1-4alkyleneO(aryl), C3-6alkynyl, C1-4alkenylO(C3-6alkynyl), C1-4alkylene(CO2H), OC1-4alkylene(CO2H), C1-4alkyleneOC1-4alkylene(CO2H), N(R18aa)C1-4alkylene(CO2H), C1-4alkylene(NR18abR18ac), OC1-4alkylene(NR18abR18ac) or N(R18aa)C1-4alkylene(NR18abR18ac); wherein said aryl, cycloalkyl or heterocycloalkyl is optionally substituted by 1, 2 or 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR18aR18b, SO2R18c, NHSO2R18c; R18ais selected from H and C1-4alkyl; R18bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R18cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; each R18aais independently selected from H and C1-4alkyl; each R18abis independently selected from H and C1-4alkyl; each R18acis independently selected from H and C1-4alkyl; or R18aband R18actogether with the nitrogen atom to which they are attached form a 4-10 membered heterocycloalkyl; R20 is H, halo, C1-4alkyl, C1-4haloalkyl or C1-4alkoxy; R21 is H, halo, C1-4alkyl, C1-4haloalkyl or C1-4alkoxy; or; R17 is H, halo, C1-4alkyl, C1-4haloalkyl, C1-4alkoxy, C1-4alkyleneOC1-4alkyl, C1- 4alkyleneOC3-6cycloalkyl or C1-4alkyleneO(4-10 membered heterocycloalkyl); R18 is H, halo, C1-4alkyl, C1-4haloalkyl, C1-4alkoxy, C1-4alkyleneOC1-4alkyl C1- 4alkyleneOC3-6cycloalkyl or C1-4alkyleneO(4-10 membered heterocycloalkyl); R20 is H, halo, C1-4alkyl, C1-4haloalkyl or C1-4alkoxy; R21 is C1-4haloalkyl, C1-4alkylene(aryl), C1-4alkylene(OH), C1-4alkylene(C3-6cycloalkyl), C1-4alkylene(4-10 membered heterocycloalkyl), 4-10 membered heterocycloalkyl, OC1-4alkylene(aryl), C1-4alkyleneOC1-4alkyl, C1-4alkyleneOC3-6cycloalkyl, C1- 4alkyleneO(4-10 membered heterocycloalkyl), C1-4alkyleneO(aryl), C3-6alkynyl, C1- 4alkenylO(C3-6alkynyl), C1-4alkylene(CO2H), OC1-4alkylene(CO2H), C1-4alkyleneOC1- 4alkylene(CO2H), N(R21aa)C1-4alkylene(CO2H), C1-4alkylene(NR21abR21ac), OC1- 4alkylene(NR21abR21ac) or N(R21aa)C1-4alkylene(NR21abR21ac); wherein said aryl, cycloalkyl or heterocycloalkyl is optionally substituted by 1, 2 or 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR21aR21b, SO2R21c, NHSO2R21c; R21a is selected from H and C1-4alkyl; R21bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R21cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; each R21aais independently selected from H and C1-4alkyl; each R21abis independently selected from H and C1-4alkyl; each R21acis independently selected from H and C1-4alkyl; or R21aband R21actogether with the nitrogen atom to which they are attached form a 4-10 membered heterocycloalkyl; wherein B is group (Ba), (Bb) or (Bc): wherein group (Ba) is: wherein: Y is C(R11)(R12), N(R13), O or S; each R10 is independently halo or C1-4alkyl; r is 0, 1, 2 or 3; R11 is H or C1-4alkyl; R12 is H or C1-4alkyl; or R11 and R12 together with the carbon atom to which they are attached form a C3-6cycloalkyl; R13 is H, C1-4alkyl or C3-6cycloalkyl; wherein said cycloalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR13aR13b, SO2R13c and NHSO2R13c; R13ais selected from H and C1-4alkyl; R13bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R13cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; wherein group (Bb) is: wherein: each R14is independently halo or C1-4alkyl; s is 0, 1, 2 or 3; wherein group (Bc) is: wherein: R15 is C1-4alkyl, C1-4alkoxy, C3-6cycloalkyl, C1-4haloalkyl, halo or CN; wherein said cycloalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR15aR15b, SO2R15c and NHSO2R15c; R15a is selected from H and C1-4alkyl; R15b is selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R15c is selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R16 is H, halo or C1-4alkyl; and D, E and F are each independently C(R16); or one of D, E and F is N, and the two remaining D, E and F groups are independently C(R16); or a pharmaceutically acceptable salt and / or solvate thereof, for use in the prevention or treatment of a disease, disorder, or condition which is an Other NLRX1-Related Disease, Disorder or Condition. Suitable substances of formula (III), and compositions containing them, and processes forpreparing them, are further described in WO2023 / 166303, which is herein incorporated byreference in its entirety. It will be understood that suitable and / or preferred substances of formula (III) may include any of the substances (generic or specific) disclosed in WO2023 / 166303.Suitably, the present invention provides a substance of formula (III), for use according to thepresent invention, wherein A is group (Aa): .Suitably, when A of the substance of formula (III), for use according to the present invention,is group (Aa), R2is halo, C1-4haloalkyl, C1-4alkylene(8-10 membered heterocycloalkyl), C1-4alkyleneO(8-10 membered heterocycloalkyl), 4-10 membered heterocycloalkyl such as 1- methyl piperazinyl, C1-4alkylene(CO2H), such as CH2CH2(CO2H), OC1-4alkylene(CO2H), C1-4alkyleneOC1-4alkylene(CO2H), N(R2aa)C1-4alkylene(CO2H), C1-4alkylene(NR2abR2ac), OC1-4alkylene(NR2abR2ac) or N(R2aa)C1-4alkylene(NR2abR2ac), in particular wherein R2is 4-10 membered heterocycloalkyl, such as 1-methyl piperazinyl, or wherein R2is C1-4alkylene(CO2H), such as CH2CH2(CO2H); and wherein R2xis H.Alternatively, when A of the substance of formula (III), for use according to the presentinvention, is group (Aa), suitably, R2x is C1-4alkylene(4-10 membered heterocycloalkyl), 4-10membered heterocycloalkyl, such as 1-methyl piperazinyl, C1-4alkyleneO(4-10 membered heterocycloalkyl), C1-4alkylene(CO2H), such as CH2CH2(CO2H), OC1-4alkylene(CO2H), C1-4alkyleneOC1-4alkylene(CO2H), N(R2xaa)C1-4alkylene(CO2H), C1-4alkylene(NR2xabR2xac), OC1-4alkylene(NR2xabR2xac) or N(R2xaa)C1-4alkylene(NR2xabR2xac), in particular wherein R2x is 4-10membered heterocycloalkyl, such as 1-methyl piperazinyl, or wherein R2x is C1- 4alkylene(CO2H), such as CH2CH2(CO2H); and wherein R2 is H.Furthermore, when A of the substance of formula (III), for use according to the presentinvention, is group (Aa), suitably, m is 2 and each R3 is independently fluoro and methyl.Suitably, the present invention provides a substance of formula (III), for use according to thepresent invention, wherein A is group (Ae): Suitably, when A of the substance of formula (III), for use according to the present invention,is group (Ae), R17is C1-4alkyl, such as methyl, ethyl or propyl, especially methyl; and / or R18is C1-4alkyl, such as methyl, ethyl or propyl, especially methyl; and / or R20is C1-4alkoxy, such as OMe or OEt, especially OM; and / or R21is H.Suitably, the present invention provides a substance of formula (III), for use according to thepresent invention, wherein B is group (Bc):Suitably, when B of the substance of formula (III), for use according to the present invention,is group (Bc), R15 is methyl, ethyl, cyclopropyl, CF3, CN, OMe, chloro or fluoro e.g. methyl, ethyl, cyclopropyl, CF3 or CN.Furthermore, when B of the substance of formula (III), for use according to the presentinvention, is group (Bc), suitably, D, E and F are C(R16) and each R16 is independently H, fluoro, chloro or methyl.For example, in one aspect, the present invention provides a substance of formula (III), foruse according to the present invention, wherein the substance of formula (III) is selectedfrom the group consisting of: (E)-3-(3-fluoro-4-methyl-5-(3-(3-methyl-1H-indazol-6-yl)acrylamido)phenyl)propanoic acid; (E)-3-(3-(3-(3-chloro-1H-indazol-6-yl)acrylamido)-5-fluoro-4-methylphenyl)propanoic acid; (E)-3-(3-fluoro-5-(3-(3-fluoro-1H-indazol-6-yl)acrylamido)-4-methylphenyl)propanoic acid; (E)-3-(3-(3-(3-cyano-1H-indazol-6-yl)acrylamido)-5-fluoro-4-methylphenyl)propanoic acid; (E)-3-(3-fluoro-5-(3-(5-fluoro-3-methyl-1H-indazol-6-yl)acrylamido)-4-methylphenyl)propanoic acid; (E)-3-(3-(3-(3-chloro-5-fluoro-1H-indazol-6-yl)acrylamido)-5-fluoro-4-methylphenyl)propanoic acid; (E)-3-(3-(3-(3,5-difluoro-1H-indazol-6-yl)acrylamido)-5-fluoro-4-methylphenyl)propanoic acid; (E)-3-(3-(3-(3-cyano-5-fluoro-1H-indazol-6-yl)acrylamido)-5-fluoro-4-methylphenyl)propanoic acid; (E)-3-(4-fluoro-3-methyl-2-(3-(3-methyl-1H-indazol-6-yl)acrylamido)phenyl)propanoic acid; (E)-3-(2-(3-(3-chloro-1H-indazol-6-yl)acrylamido)-4-fluoro-3-methylphenyl)propanoic acid; (E)-3-(4-fluoro-2-(3-(3-fluoro-1H-indazol-6-yl)acrylamido)-3-methylphenyl)propanoic acid; (E)-3-(2-(3-(3-cyano-1H-indazol-6-yl)acrylamido)-4-fluoro-3-methylphenyl)propanoic acid; (E)-3-(4-fluoro-2-(3-(5-fluoro-3-methyl-1H-indazol-6-yl)acrylamido)-3-methylphenyl)propanoic acid; (E)-3-(2-(3-(3-chloro-5-fluoro-1H-indazol-6-yl)acrylamido)-4-fluoro-3-methylphenyl)propanoic acid; (E)-3-(2-(3-(3,5-difluoro-1H-indazol-6-yl)acrylamido)-4-fluoro-3-methylphenyl)propanoic acid; (E)-3-(2-(3-(3-cyano-5-fluoro-1H-indazol-6-yl)acrylamido)-4-fluoro-3-methylphenyl)propanoic acid; (E)-N-(6-methoxy-2,4-dimethylpyridin-3-yl)-3-(3-methyl-1H-indazol-6-yl)acrylamide; (E)-3-(3-chloro-1H-indazol-6-yl)-N-(6-methoxy-2,4-dimethylpyridin-3-yl)acrylamide; (E)-3-(3-fluoro-1H-indazol-6-yl)-N-(6-methoxy-2,4-dimethylpyridin-3-yl)acrylamide; (E)-3-(3-cyano-1H-indazol-6-yl)-N-(6-methoxy-2,4-dimethylpyridin-3-yl)acrylamide; (E)-3-(5-fluoro-3-methyl-1H-indazol-6-yl)-N-(6-methoxy-2,4-dimethylpyridin-3-yl)acrylamide; (E)-3-(3-chloro-5-fluoro-1H-indazol-6-yl)-N-(6-methoxy-2,4-dimethylpyridin-3-yl)acrylamide; (E)-3-(3,5-difluoro-1H-indazol-6-yl)-N-(6-methoxy-2,4-dimethylpyridin-3-yl)acrylamide; (E)-3-(3-cyano-5-fluoro-1H-indazol-6-yl)-N-(6-methoxy-2,4-dimethylpyridin-3-yl)acrylamide; (E)-N-(3-fluoro-2-methyl-6-(4-methylpiperazin-1-yl)phenyl)-3-(3-methyl-1H-indazol-6- yl)acrylamide; (E)-3-(3-chloro-1H-indazol-6-yl)-N-(3-fluoro-2-methyl-6-(4-methylpiperazin-1- yl)phenyl)acrylamide; (E)-3-(3-fluoro-1H-indazol-6-yl)-N-(3-fluoro-2-methyl-6-(4-methylpiperazin-1- yl)phenyl)acrylamide; (E)-3-(3-cyano-1H-indazol-6-yl)-N-(3-fluoro-2-methyl-6-(4-methylpiperazin-1- yl)phenyl)acrylamide; (E)-N-(3-fluoro-2-methyl-6-(4-methylpiperazin-1-yl)phenyl)-3-(5-fluoro-3-methyl-1H-indazol- 6-yl)acrylamide; (E)-3-(3-chloro-5-fluoro-1H-indazol-6-yl)-N-(3-fluoro-2-methyl-6-(4-methylpiperazin-1- yl)phenyl)acrylamide; (E)-3-(3,5-difluoro-1H-indazol-6-yl)-N-(3-fluoro-2-methyl-6-(4-methylpiperazin-1- yl)phenyl)acrylamide; and (E)-3-(3-cyano-5-fluoro-1H-indazol-6-yl)-N-(3-fluoro-2-methyl-6-(4-methylpiperazin-1- yl)phenyl)acrylamide, or a pharmaceutically acceptable salt and / or solvate of any one thereof.In an alternative aspect, the present invention provides a substance of formula (III), for useaccording to the present invention, wherein the substance of formula (III) is selected from thegroup consisting of: (2E)-N-(6-methoxy-2,4-dimethylpyridin-3-yl)-3-(3-methyl-1H-indazol-6-yl)prop-2-enamide; (2E)-3-(3-fluoro-1H-indazol-6-yl)-N-(6-methoxy-2,4-dimethylpyridin-3-yl) prop-2-enamide ; (2E)-3-(3-cyano-1H-indazol-6-yl)-N-(6-methoxy-2,4-dimethylpyridin-3-yl)prop-2-enamide; (2E)-3-(5-fluoro-3-methyl-1H-indazol-6-yl)-N-(6-methoxy-2,4-dimethylpyridin-3-yl)prop-2- enamide; (2E)-3-(3-chloro-5-fluoro-1H-indazol-6-yl)-N-(6-methoxy-2,4-dimethylpyridin-3-yl)prop-2- enamide; (2E)-3-(3,5-difluoro-1H-indazol-6-yl)-N-(6-methoxy-2,4-dimethylpyridin-3-yl)prop-2-enamide; (2E)-3-(3-cyano-5-fluoro-1H-indazol-6-yl)-N-(6-methoxy-2,4-dimethylpyridin-3-yl)prop-2- enamide; (2E)-N-(5-fluoro-2,4-dimethylpyridin-3-yl)-3-(5-fluoro-3-methyl-1H-indazol-6-yl)prop-2- enamide; (2E)-3-(3-fluoro-1H-indazol-6-yl)-N-(5-fluoro-2,4-dimethylpyridin-3-yl)prop-2-enamide; (2E)-3-(3-chloro-5-fluoro-1H-indazol-6-yl)-N-(5-fluoro-2,4-dimethylpyridin-3-yl) prop-2- enamide; (2E)-N-(5-fluoro-4-methylpyridin-3-yl)-3-(3-methyl-1H-indazol-6-yl)prop-2-enamide; (2E)-3-(3,5-difluoro -1H-indazol-6-yl)-N-(5-fluoro-2,4-dimethylpyridin-3-yl)prop-2-enamide; (2E)-3-(3-chloro-1H-indazol -6-yl)-N-(5-fluoro-2,4-dimethylpyridin-3-yl)prop-2-enamide; (2E)-N-(5-fluoro-2,4-dimethylpyridin-3-yl)-3-(3-methyl-1H-indazol-6-yl)prop-2-enamide; (2E)-N-[5-fluoro-4-(methoxymethyl)pyridin-3-yl]-3-(3-methyl-1H-indazol-6-yl)prop-2-enamide; (2E)-3-(3-methyl-1H-indazol-6-yl)-N-(2-methylpyridin-3-yl)prop-2-enamide; (2E)-N-(2,4-dimethylpyridin-3-yl)-3-(3-methyl-1H-indazol-6-yl)prop-2-enamide; (2E)-N-[5-fluoro-4-(methoxymethyl)-2-methylpyridin-3-yl]-3-(3-methyl-1H-indazol-6-yl)prop-2- enamide; or a pharmaceutically acceptable salt and / or solvate of any one thereof.In another aspect, the present invention provides a substance of formula (IV): wherein: R1 is H or F; wherein: R2 is C1-3alkyl, -CH2OC1-3alkyl, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3-5cycloalkyl; R3 is H, C1-3alkyl, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3-5cycloalkyl; R4is H, C1-3alkyl, -CH2OC1-3alkyl, C1-3fluoroalkyl, C1-3alkoxy, C1-3fluoroalkoxy, -CN, halo or C3-5cycloalkyl; and R5 is H, C1-3alkyl, -CH2OC1-3alkyl, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3- 5cycloalkyl; provided that when R5 is H then R1 is F; B is group (Ba) or (Bb): wherein group (Ba) is: wherein: Y is C(R9a)(R9b), O or N(R9c); R9a, R9b and R9c are independently H or C1-3alkyl or R9a and R9b together with the carbon atom to which they are attached form a C3-6cycloalkyl group; and R6, R7 and R8 are independently H, C1-3alkyl, C2-3alkynyl, C1-3fluoroalkyl, C1-3alkoxy, - CN, halo or C3-5cycloalkyl; wherein group (Bb) is: wherein: R10is H, C1-3alkyl, C2-3alkynyl, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3-5cycloalkyl; D is N or C(R11) and R11, R12and R13are independently H, C1-3alkyl, C2-3alkynyl, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3-5cycloalkyl; or a prodrug thereof in which an available nitrogen atom in group Ba or Bb is derivatised by the moiety -CH2-OP(=O)(OH)2; or a pharmaceutically acceptable salt and / or solvate thereof, for use in the prevention or treatment of a disease, disorder, or condition which is an Other NLRX1-Related Disease, Disorder or Condition.Suitably, the substance of formula (IV) for use according to the present invention, is asubstance of formula (IVA): wherein: R2is C1-3alkyl, -CH2OC1-3alkyl, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3-5cycloalkyl; R3is H, C1-3alkyl, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3-5cycloalkyl; R4is H, C1-3alkyl, -CH2OC1-3alkyl, C1-3fluoroalkyl, C1-3alkoxy, C1-3fluoroalkoxy, -CN, halo or C3-5cycloalkyl; and R5 is H, C1-3alkyl, -CH2OC1-3alkyl, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3-5cycloalkyl; B is group (Ba) or (Bb): wherein group (Ba) is: wherein: Y is C(R9a)(R9b), O or N(R9c); R9a, R9b and R9c are independently H or C1-3alkyl or R9a and R9b together with the carbon atom to which they are attached form a C3-6cycloalkyl group; and R6and R8are independently H, C1-3alkyl, C2-3alkynyl, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3-5cycloalkyl; wherein group (Bb) is: wherein: R10 is H, C1-3alkyl, C2-3alkynyl, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3-5cycloalkyl; D is N or C(R11) and R11 and R13 are independently H, C1-3alkyl, C2-3alkynyl, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3-5cycloalkyl; or a prodrug thereof in which an available nitrogen atom in group Ba or Bb is derivatised by the moiety -CH2-OP(=O)(OH)2; or a pharmaceutically acceptable salt and / or solvate thereof.Suitably, the present invention provides a substance of formula (IVA), or prodrug thereof, foruse according to the present invention, wherein B is group (Ba1):Suitably, when B of the substance of formula (IVA), for use according to the present invention,is group (Ba1), R8 is F. Alternatively, when B of the substance of formula (IVA), for useaccording to the present invention, is group (Ba1), R8 is H. Moreover, when B of the substanceof formula (IVA), for use according to the present invention, is group (Ba1), R6 is H.Furthermore, when B of the substance of formula (IVA), for use according to the presentinvention, is group (Ba1), Y is CH2. Alternatively, when B of the substance of formula (IVA), foruse according to the present invention, is group (Ba1), Y is NMe.Suitably, the present invention provides a substance of formula (IVA), or prodrug thereof, foruse according to the present invention, wherein B is group (Bb1): Suitably, when B of the substance of formula (IVA), for use according to the present invention,is group (Bb1), D is N. Alternatively, when B of the substance of formula (IVA), for useaccording to the present invention, is group (Bb1), D is C(R11) and R11is F, Cl, -CN, OMe,preferably wherein D is C(R11) and R11 is F. Alternatively, when B of the substance of formula(IVA), for use according to the present invention, is group (Bb1), D is C(R11) and R11 is H.Moreover, when B of the substance of formula (IVA), for use according to the present invention,is group (Bb1), R13 is suitably H. Furthermore, when B of the substance of formula (IVA), foruse according to the present invention, is group (Bb1), R10 is suitably H, Cl, F, Me or -CN,preferably H, Cl, Me or -CN.Suitably, the present invention provides a substance of formula (IVA), or prodrug thereof, foruse according to the present invention, wherein R2 is Me. Moreover, suitably, the presentinvention provides a substance of formula (IVA), for use according to the present invention,wherein R5 is C1-3alkyl, -CH2OMe, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3-5cycloalkyl, preferably is Me, F or Cl more preferably is Me or Cl.In one aspect of the invention, there is provided a substance of formula (IVA), or prodrugthereof, for use according to the present invention, wherein R3is Me, R4is H and R5is Me, For Cl e.g. is Me or Cl. In an alternative aspect of the invention, there is provided a substanceof formula (IVA), for use according to the present invention, wherein R2is Me, R3is Me, R4is methoxy and R5is H.Suitably, the substance of formula (IV) for use according to the present invention, is asubstance of formula (IVB): wherein: R2is C1-3alkyl, -CH2OC1-3alkyl, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3-5cycloalkyl; R3 is H, C1-3alkyl, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3-5cycloalkyl; R4 is H, C1-3alkyl, -CH2OC1-3alkyl, C1-3fluoroalkyl, C1-3alkoxy, C1-3fluoroalkoxy -CN, halo or C3-5cycloalkyl; and R5 is F, Cl or -CN; B is group (Ba) or (Bb): wherein group (Ba) is: wherein: Y is C(R9a)(R9b), O or N(R9c); R9a, R9b and R9c are independently H or C1-3alkyl or R9a and R9b together with the carbon atom to which they are attached form a C3-6cycloalkyl group; and R6, R7and R8are independently H, C1-3alkyl, C2-3alkynyl, C1-3fluoroalkyl, C1-3alkoxy, - CN, halo or C3-5cycloalkyl; wherein group (Bb) is: wherein: R10 is H, C1-3alkyl, C2-3alkynyl, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3-5cycloalkyl; D is N or C(R11) and R11, R12 and R13 are independently H, C1-3alkyl, C2-3alkynyl, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3-5cycloalkyl; or a prodrug thereof in which an available nitrogen atom in group Ba or Bb is derivatised by the moiety -CH2-OP(=O)(OH)2; or a pharmaceutically acceptable salt and / or solvate thereof.Suitably, the present invention provides a substance of formula (IVB), or prodrug thereof, foruse according to the present invention, wherein B is group (Ba). Suitably, when B of thesubstance of formula (IVB), for use according to the present invention, is group (Ba), suitablyR7 is F and R6 and R8 are each H. Alternatively, when B of the substance of formula (IVB), foruse according to the present invention, is group (Ba), suitably R8 is F and R6 and R7 are eachH. Moreover, when B of the substance of formula (IVB), for use according to the presentinvention, is group (Ba), suitably Y is N(Me).Alternatively, the present invention provides a substance of formula (IVB), or prodrug thereof,for use according to the present invention, wherein B is group (Bb). Suitably, when B of thesubstance of formula (IVB), for use according to the present invention, is group (Bb), suitablyD is C(R11) and R11 is F. Alternatively, when B of the substance of formula (IVB), for useaccording to the present invention, is group (Bb), suitably, D is C(R11) and R11is H. Moreover,when B of the substance of formula (IVB), for use according to the present invention, is group(Bb), R12 and R13 are suitably H. Furthermore, when B of the substance of formula (IVB), foruse according to the present invention, is group (Bb), R10is suitably selected from H, Cl, Me and -CN.In one aspect of the invention, there is provided a substance of formula (IVB), or prodrugthereof, for use according to the present invention, wherein R2is suitably Me, -(CH2)OMe or -CN. In a further aspect, of the invention, there is provided a substance of formula (IVB), orprodrug thereof, for use according to the present invention, suitably wherein R2is Me, R3is H,R4 is H and R5 is Cl. Alternatively, there is provided a substance of formula (IVB), or prodrug thereof, for use according to the present invention, suitably wherein R2is Me, R3is H, R4is Hand R5 is F; or R2 is -(CH2)OMe, R3 is H, R4 is H and R5 is F; or R2 is -(CH2)OMe, R3 is H, R4is H and R5 is Cl; or R2 is Me, R3 is H, R4 is H and R5 is -CN; or R2 is -CN, R3 is H, R4 is H andR5 is Cl; or R2 is Me, R3 is H, R4 is H and R5 is Me.For example, in one aspect of the invention, the present invention provides a substance offormula (IV), for use according to the present invention, wherein the substance of formula(IV) is selected from the group consisting of: (2Z)-2-fluoro-3-(7-fluoro-1H-indazol-6-yl)-N-(5-fluoro-2,4-dimethylpyridin-3-yl)prop-2- enamide; (2Z)-2-fluoro-3-(3-fluoro-1H-indazol-6-yl)-N-(5-fluoro-2,4-dimethylpyridin-3-yl) prop-2- enamide; (2Z)-N-(2,5-dimethylpyridin-3-yl)-2-fluoro-3-(3-methyl-1H-indazol-6-yl)prop-2-enamide; (2Z)-N-(5-chloro-2-methylpyridin-3-yl)-2-fluoro-3-(3-methyl-1H-indazol-6-yl)prop-2-enamide; (2Z)-2-fluoro-N-(6-methoxy-2,4-dimethylpyridin-3-yl)-3-(3-methyl-1H-indazol-6-yl)prop-2- enamide; (2Z)-2-fluoro-3-(7-fluoro-1H-indazol-6-yl)-N-(6-methoxy-2,4-dimethylpyridin-3-yl)prop-2- enamide; (2Z)-2-fluoro-N-(5-fluoro-2,4-dimethylpyridin-3-yl)-3-(3-methyl-1H-indazol-6-yl)prop-2- enamide; (2E)-N-(5-chloro-2-methylpyridin-3-yl)-3-(3-methyl-1H-indazol-6-yl)prop-2-enamide; (2E)-3-(3-chloro-1H-indazol-6-yl)-N-[5-fluoro-2-(methoxymethyl)pyridin-3-yl]prop-2-enamide; (2E)-3-(3-chloro-1H-indazol-6-yl)-N-(5-fluoro-2-methylpyridin-3-yl)prop-2-enamide; (2E)-N-(5-fluoro-2-methylpyridin-3-yl)-3-(3-methyl-1H-indazol-6-yl)prop-2-enamide; (Z)-3-(7-chloro-1H-indazol-6-yl)-2-fluoro-N-(6-methoxy-2,4-dimethylpyridin-3-yl)acrylamide; (2E)-N-(5-chloro-2-methylpyridin-3-yl)-3-(4-fluoro-1-methyl-2-oxo-3H-1,3-benzodiazol-5- yl)prop-2-enamide; (2Z)-2-fluoro-3-(4-fluoro-1-methyl-2-oxo-3H-1,3-benzodiazol-5-yl)-N-(5-fluoro-2,4- dimethylpyridin-3-yl)prop-2-enamide; (2Z)-3-(3-cyano-7-fluoro-1H-indazol-6-yl)-2-fluoro-N-(5-fluoro-2,4-dimethylpyridin-3-yl)prop- 2-enamide; (2E)-N-[5-chloro-2-(methoxymethyl)pyridin-3-yl]-3-(7-fluoro-1H-indazol-6-yl)prop-2-enamide; (2Z)-N-(5-chloro-2-methylpyridin-3-yl)-3-(3-cyano-1H-indazol-6-yl)-2-fluoroprop-2-enamide; (2Z)-N-(5-chloro-2,4-dimethylpyridin-3-yl)-2-fluoro-3-(3-methyl-1H-indazol-6-yl)prop-2- enamide; (2Z)-3-(3-chloro-7-fluoro-1H-indazol-6-yl)-2-fluoro-N-(5-fluoro-2,4-dimethylpyridin-3-yl)prop- 2-enamide; (2Z)-3-(3-cyano-1H-indazol-6-yl)-2-fluoro-N-(5-fluoro-2,4-dimethylpyridin-3-yl)prop-2- enamide; (2Z)-N-(2,5-dimethylpyridin-3-yl)-3-(3-cyano-1H-indazol-6-yl)-2-fluoroprop-2-enamide); (2Z)-3-(3-chloro-1H-indazol-6-yl)-2-fluoro-N-(5-fluoro-2,4-dimethylpyridin-3-yl)prop-2- enamide; (Z)-2-fluoro-3-(7-methoxy-1H-indazol-6-yl)-N-(6-methoxy-2,4-dimethylpyridin-3- yl)acrylamide; (Z)-2-fluoro-3-(7-fluoro-1H-indazol-6-yl)-N-(2,4,5-trimethylpyridin-3-yl)acrylamide; and (Z)-2-fluoro-3-(7-fluoro-1H-indazol-6-yl)-N-(2,4,5-trimethylpyridin-3-yl)acrylamide or a pharmaceutically acceptable prodrug, salt and / or solvate of any one thereof.In another aspect, the present invention provides a substance of formula (V): wherein: R1is H or C1-4alkyl; R2is H, halo, C1-4alkyl, C1-4haloalkyl; C1-4alkoxy, C1-4haloalkoxy or C0-4alkylene(OH); R3is H, halo or C1-4alkyl; R4is H, halo or C1-4alkyl; R5is halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C2-6alkenyl, C2- 6haloalkenyl, C0-6alkylene(C3-6cycloalkyl), C0-6alkylene(OH); or R4and R5together with the carbon atom to which they are attached form aC5-11 spiro carbocyclyl, 4 to 7 membered heterocycle or C3-6cycloalkyl wherein said spiro carbocyclyl,heterocycloalkyl or cycloalkyl may be optionally substituted by one or more groups selected from C1-3alkyl, C1-3haloalkyl and halo; R6is H or C1-4alkyl; R7is H, halo, C1-4alkyl, C1-4haloalkyl, C1-4alkoxy or C1-4haloalkoxy; A is a monocyclic or bicyclic aryl or a monocyclic or bicyclic heteroaryl optionally substituted by one or more A1; A1is independently selected from the group consisting of: C1-3alkylthio, halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C3-6cycloalkyl, CN, OH, NRgRh, or NHSO2Rj; Rgis H or C1-4alkyl; Rhis H or C1-4alkyl; Rjis C1-4alkyl; or when A represents phenyl substituted by one or more A1, R5together with a substituent A1in the ortho position are joined and together represent (CH2)vwherein v represents 1, 2 or 3 and wherein one of the said CH2groups may optionally be replaced by O; B is a monocyclic or bicyclic heterocycle or a monocyclic or bicyclic heteroaryl wherein said heterocycle or heteroaryl may be optionally substituted by one or more B1; B1is halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, oxo (=O), or thiooxo (=S), C0-6alkylene(OH);or a salt and / or solvate thereof for use in the prevention or treatment of a disease, disorder, orcondition which is an Other NLRX1-Related Disease, Disorder or Condition. Suitable substances of formula (V), and compositions containing them, and processes for preparing them, are further described in PCT / GB2024 / 050146, which is herein incorporatedby reference in its entirety and in the Examples section below. mPTP Inhibitor 1, furtherdescribed in the Examples section, is an example of this genus. It will be understood that suitable and / or preferred substances of formula (V) may include any of the substances (generic or specific) disclosed in PCT / GB2024 / 050146.Suitably, the present invention provides a substance of formula (VA) for use according to thepresent invention: wherein: R1is H or C1-4alkyl; R2is H, halo, C1-4alkyl, C1-4haloalkyl; C1-4alkoxy, C1-4haloalkoxy or C0-4alkylene(OH); R3is H, halo or C1-4alkyl; R4is H or C1-4alkyl; R5is H, halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C2-6alkenyl, C2-6haloalkenyl, C0-6alkylene(C3-6cycloalkyl), C0-6alkylene(OH); or R4and R5together with the atom to which they are attached form a C3-6cycloalkyl wherein said cycloalkyl may be optionally substituted by one or more groups selected from C1-3alkyl, C1-3haloalkyl and halo; R6is H or C1-4alkyl; R7is H, halo , C1-4alkyl, C1-4haloalkyl, C1-4alkoxy or C1-4haloalkoxy; A is a monocyclic or bicyclic aryl or a monocyclic or bicyclic heteroaryl optionally substituted by one or more A1; A1is halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C3-6cycloalkyl, CN, OH, NRgRh, or NHSO2Rj; Rgis H or C1-4alkyl; Rhis H or C1-4alkyl; Rjis C1-4alkyl; or when A represents phenyl substituted by one or more A1, R5together with a substituent A1in the ortho position are joined and together represent (CH2)vwherein v represents 1, 2 or 3 and wherein one of the said CH2groups may optionally be replaced by O; B is a monocyclic or bicyclic heterocycle or a monocyclic or bicyclic heteroaryl which may be optionally substituted by one or more B1; B1is halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy or C0-6alkylene(OH); or a salt and / or solvate thereof. In a most suitable embodiment, for example wherein R4is H, R4and R5have the following stereochemistry: . R4and R5may also have the following stereochemistry: . Mixtures of enantiomers including racemic mixtures of compound of formula (V) and (VA) with respect to the chiral centre shown are also provided.In one aspect of the present invention, there is provided a substance of formula (V) or (VA),for use according to the present invention, suitably wherein R1, R2 and R3 are each H.Moreover, suitably, the present invention provides a substance of formula (V) or (VA), foruse according to the present invention, wherein R4 is H or methyl, particularly H.Furthermore, suitably, the present invention provides a substance of formula (V) or (VA), for use according to the present invention, wherein R5is C1-6alkyl, such as methyl, ethyl, n-propyl or iso-propyl, especially ethyl. In an alternative suitable aspect, the present inventionprovides a substance of formula (V) or (VA), for use according to the present invention,wherein R5 is C0-6alkylene(C3-6cycloalkyl), such as C3-6cycloalkyl, for example cyclopropyl orcyclobutyl, especially cyclopropyl. In a further alternative aspect, suitably, the presentinvention provides a substance of formula (V) or (VA), for use according to the presentinvention, wherein R4 and R5 together with the atom to which they are attached form a C3-6cycloalkyl, such as a cyclopropyl, cyclobutyl or cyclopentyl ring, especially a cyclobutyl ring.In addition, suitably, the present invention provides a substance of formula (V) or (VA), foruse according to the present invention, wherein R6is H and R7is H. Suitably, in one aspect of the present invention, there is provided a substance of formula (V) or (VA), for use according to the present invention, wherein A is phenyl. For example, in one aspect of the present invention, there is provided a substance of formula (V) or (VA), for useaccording to the present invention, wherein A is selected from the group consisting of: wherein: A1Ais halo, such as F, Br or Cl; C1-6alkyl, such as methyl; or C1-6alkoxy, such as OMe; and A1Bis H or halo, such as F, Br or Cl, especially F. In one aspect of the present invention, there is provided a substance of formula (V) or (VA), for use according to the present invention, wherein B is selected from the group consisting of: such, wherein: B1Ais H or C1-6alkyl, such as methyl; and B2Ais H or C1-6alkyl, such as methyl. For example, in one aspect of the invention, the present invention provides a substance offormula (V) or (VA), for use according to the present invention, wherein the substance offormula (V) or (VA) is selected from the group consisting of:N-((1-benzylcyclobutyl)methyl)-5-hydroxynicotinamide; N-((1-benzylcyclobutyl)methyl)-5-hydroxy-6-methylnicotinamide; N-((1-benzylcyclobutyl)methyl)-5-hydroxy-4-methylnicotinamide; N-((1-benzylcyclobutyl)methyl)-1H-1,2,3-triazole-5-carboxamide; N-((1-benzylcyclobutyl)methyl)-2-oxo-2,3-dihydropyrimidine-4-carboxamide; N-((1-benzylcyclobutyl)methyl)-6-oxo-1,6-dihydropyrimidine-2-carboxamide; N-((1-benzylcyclobutyl)methyl)-5-oxo-2,5-dihydro-1H-1,2,4-triazole-3-carboxamide; N-((1-benzylcyclobutyl)methyl)-5-methyl-6-oxo-1,6-dihydropyrimidine-2-carboxamide; N-((1-benzylcyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide; N-((1-benzylcyclobutyl)methyl)-6-hydroxy-N-methylpyrazine-2-carboxamide; N-(2,2-dimethyl-3-phenylpropyl)-6-hydroxypyrazine-2-carboxamide; N-((1-(2-fluorobenzyl)cyclobutyl)methyl)-6-hydroxypyrazine-2-carboxamide; N-((1-benzylcyclobutyl)methyl)-1-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide; N-((1-(2,6-difluorobenzyl)cyclobutyl)methyl)-6-oxo-1,6-dihydropyrazine-2-carboxamide; N-((1-(2,4-difluorobenzyl)cyclobutyl)methyl)-6-oxo-1,6-dihydropyrazine-2-carboxamide; N-((1-(2,3-difluorobenzyl)cyclobutyl)methyl)-6-oxo-1,6-dihydropyrazine-2-carboxamide; N-((1-benzylcyclopentyl)methyl)-6-oxo-1,6-dihydropyrazine-2-carboxamide; N-((1-(2-methylbenzyl)cyclobutyl)methyl)-6-oxo-1,6-dihydropyrazine-2-carboxamide; N-((1-(2-fluorobenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(2,6-difluorobenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(2,4-difluorobenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-(1-(1-benzylcyclobutyl)ethyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3 carboxamide; N-(1-(1-benzylcyclobutyl)ethyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide; 1-methyl-5-oxo-N-((1-(1-phenylethyl)cyclobutyl)methyl)-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; 1-methyl-5-oxo-N-((1-(1-phenylethyl)cyclobutyl)methyl)-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(methoxy(phenyl)methyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; 1-methyl-N-((1-(2-methylbenzyl)cyclobutyl)methyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(2-chlorobenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-(2,2-dimethyl-3-phenylpropyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; 1-methyl-N-(2-methyl-3-phenylpropyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide; N-((1-benzylcyclopropyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-(2,2-dimethyl-1-phenylpentan-3-yl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; 1-methyl-5-oxo-N-(1,1,1-trifluoro-3,3-dimethyl-4-phenylbutan-2-yl)-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-(3-(2-bromophenyl)-2,2-dimethylpropyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(2-bromobenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-(3,3-dimethyl-4-phenylbutan-2-yl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-(3,3-dimethyl-4-phenylbutan-2-yl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-(2-benzylbutyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide; N-(2-benzyl-3-hydroxy-2-methylpropyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-(2-benzyl-3-hydroxy-2-methylbutyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-(2-methoxy-3-phenylpropyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide; N-(2-benzyl-2-methylbutyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide; N-((1-benzylcyclohexyl)methyl)-6-oxo-1,6-dihydropyrazine-2-carboxamide; N-((1-benzyl-3,3-difluorocyclobutyl)methyl)-6-oxo-1,6-dihydropyrazine-2-carboxamide; N-((1-(3-fluorobenzyl)cyclobutyl)methyl)-6-hydroxypyrazine-2-carboxamide; N-((1-(4-fluorobenzyl)cyclobutyl)methyl)-6-hydroxypyrazine-2-carboxamide; N-(2-cyclobutyl-3-phenylpropyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(1-(2,4-difluorophenyl)ethyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-(2-cyclopropyl-3-phenylpropyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-(2-benzylbutyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide; N-(2-benzylpentyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide; N-(2,2-dimethyl-3-phenylpropyl)-6-oxo-1,6-dihydropyridazine-3-carboxamide; N-(2,2-dimethyl-3-phenylpropyl)-2-oxo-2,3-dihydrobenzo[d]oxazole-5-carboxamide; 1-methyl-N-((2-methyl-2,3-dihydro-1H-inden-2-yl)methyl)-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; 1-methyl-N-(3-methyl-3-phenylbutyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide; 1-methyl-5-oxo-N-((1,2,3,4-tetrahydronaphthalen-2-yl)methyl)-4,5-dihydro-1H-1,2,4-triazole- 3-carboxamide; N-((1-(2-methoxybenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; 6-oxo-N-((1-(pyridin-2-ylmethyl)cyclobutyl)methyl)-1,6-dihydropyrazine-2-carboxamide; N-((1-benzylcyclobutyl)methyl)-1-methyl-2-oxo-2,3-dihydro-1H-imidazole-4-carboxamide; N-(2-benzyl-3-hydroxypropyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide; N-(2,2-dimethyl-3-phenylpropyl)-N,1-dimethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(2,4-Difluorobenzyl)cyclohexyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((2S,3S)-3-Benzylpentan-2-yl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(3-Methoxybenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(2-(Difluoromethyl)benzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-((1-(3-Cyclopropylbenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole- 3-carboxamide; N-(2-Cyclopropyl-3-(3-fluorophenyl)propyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(3-Chlorobenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; 1-Methyl-5-oxo-N-(2-(thiophen-2-ylmethyl)butyl)-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(2,5-Difluorobenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(2-Ethylbenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(2-Fluoro-5-methylbenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-((1-(3-Fluorobenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(3-Chloro-2-fluorobenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-((1-(4-Fluoro-2-methylbenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-((1-(4-Fluoro-2-(trifluoromethyl)benzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H- 1,2,4-triazole-3-carboxamide; N-((1-Benzylcyclobutyl)methyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazole-3-carboxamide; 1-Methyl-N-((1-(3-methylbenzyl)cyclobutyl)methyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(4-Chloro-2-fluorobenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-((1-(4-Chloro-2-methylbenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-((1-(2,4-Difluorobenzyl)cyclopentyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole- 3-carboxamide; N-(2-Cyclopropyl-3-(2,4-difluorophenyl)propyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole- 3-carboxamide; N-((1-(2-Fluoro-3-methylbenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-((1-(2,3-Difluorobenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-(2-Cyclopropyl-3-(2,4-difluorophenyl)propyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole- 3-carboxamide; N-(2-(2,4-Difluorobenzyl)butyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide; N-((1-(3-Bromobenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(3-Cyanobenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(3,5-difluorobenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-(2-cyclopropyl-3-(2,4,6-trifluorophenyl)propyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide N-(2-cyclopropyl-3-(3,4-difluorophenyl)propyl)-1-methyl-5-thioxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-((1-(2,4-difluorobenzyl)cyclobutyl)methyl)-1-methyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazole- 3-carboxamide; N-((2-(2,4-difluorobenzyl)tetrahydrofuran-2-yl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-((4-(2,4-difluorobenzyl)tetrahydro-2H-pyran-4-yl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H- 1,2,4-triazole-3-carboxamide; N-((1-(2,4-difluorobenzyl)spiro[2.2]pentan-1-yl)methyl)-6-oxo-1,6-dihydropyrazine-2- carboxamide; N-((1-(2,4-difluorobenzyl)spiro[2.2]pentan-1-yl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-(2-cyclopropyl-3-phenylpropyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; 1-methyl-5-oxo-N-(2-(2,4,6-trifluorobenzyl)butyl)-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(2,4-difluorobenzyl)cyclobutyl)methyl)-4-hydroxypicolinamide; N-(2-(2,4-difluorobenzyl)-2-fluorobutyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(2,4-difluorobenzyl)cyclobutyl)methyl)-5-hydroxy-1-methyl-1H-pyrazole-3-carboxamide; N-(2-cyclopropyl-3-(4-fluoro-2-methylphenyl)propyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-((1-(2,4-difluorobenzyl)cyclobutyl)methyl)-5-oxo-4,5-dihydropyrazine-2-carboxamide; N-((1-(3,4-difluorobenzyl)cyclobutyl)methyl)-6-oxo-1,6-dihydropyrimidine-2-carboxamide; N-3-benzylpentan-2-yl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide; N-(2-cyclopropyl-3-(2,4-difluorophenyl)propyl)-3-oxo-2,3-dihydroisoxazole-5-carboxamide; N-(2-cyclopropyl-3-(2,4-difluorophenyl)propyl)-2-oxo-2,3-dihydrooxazole-4-carboxamide; N-((1-(3,4-difluorobenzyl)cyclobutyl)methyl)-6-oxo-1,6-dihydropyrazine-2-carboxamide; N-(-3-(2,4-difluorobenzyl)pentan-2-yl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(3,4-difluorobenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-(2-cyclopropyl-3-(3,4-difluorophenyl)propyl)-6-oxo-1,6-dihydropyrimidine-2-carboxamide; N-((1-(2,5-difluorobenzyl)cyclobutyl)methyl)-6-oxo-1,6-dihydropyrimidine-2-carboxamide; 6-oxo-N-((1-(2,4,5-trifluorobenzyl)cyclobutyl)methyl)-1,6-dihydropyrazine-2-carboxamide; N-(2-cyclopropyl-3-(2,4-difluorophenyl)propyl)-6-oxo-1,6-dihydropyrimidine-2-carboxamide; N-(2-cyclopropyl-3-(3,4-difluorophenyl)propyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole- 3-carboxamide; N-(2-cyclopropyl-3-(3,4-difluorophenyl)propyl)-6-oxo-1,6-dihydropyrazine-2-carboxamide; N-((1-(2,4-difluorobenzyl)cyclopentyl)methyl)-6-oxo-1,6-dihydropyrazine-2-carboxamide; N-(2-cyclopropyl-3-(2,5-difluorophenyl)propyl)-6-oxo-1,6-dihydropyrimidine-2-carboxamide; N-(2-cyclopropyl-3-(2,4-difluorophenyl)propyl)-6-oxo-1,6-dihydropyrazine-2-carboxamide; N-(2-cyclopropyl-3-(2,5-difluorophenyl)propyl)-6-oxo-1,6-dihydropyridazine-3-carboxamide; 1-methyl-5-oxo-N-((1-(2,3,4-trifluorobenzyl)cyclobutyl)methyl)-4,5-dihydro-1H-1,2,4-triazole- 3-carboxamide; 1-methyl-5-oxo-N-((1-(2,4,5-trifluorobenzyl)cyclobutyl)methyl)-4,5-dihydro-1H-1,2,4-triazole- 3-carboxamide; N-(2-cyclopropyl-3-(2,5-difluorophenyl)propyl)-6-oxo-1,6-dihydropyrazine-2-carboxamide; N-(2-cyclopropyl-3-(2,5-difluorophenyl)propyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole- 3-carboxamide; N-((1-(2,4-difluorobenzyl)cyclobutyl)methyl)-6-oxo-1,6-dihydropyrimidine-2-carboxamide; N-((1-(3-ethylbenzyl)cyclobutyl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-(2-(2,4-difluorobenzyl)butyl)-6-oxo-1,6-dihydropyrazine-2-carboxamide; N-(2-(3,4-difluorobenzyl)butyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide; N-((1-(4-fluoro-2-methylbenzyl)cyclobutyl)methyl)-6-oxo-1,6-dihydropyrazine-2-carboxamide; N-((1-(4-fluoro-2-methylbenzyl)cyclobutyl)methyl)-6-oxo-1,6-dihydropyrimidine-2- carboxamide; N-((1-(2,4-difluorobenzyl)cyclobutyl)methyl)-1H-1,2,3-triazole-5-carboxamide; N-((1-(2,4-difluorobenzyl)cyclobutyl)methyl)-4H-1,2,4-triazole-3-carboxamide; N-(2-((2,3-dihydrobenzofuran-5-yl)methyl)butyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-((1-(2,5-difluorobenzyl)cyclobutyl)methyl)-6-oxo-1,6-dihydropyrazine-2-carboxamide; N-((1-(2,4-difluorobenzyl)cyclobutyl)methyl)-6-oxo-1,6-dihydropyridazine-3-carboxamide; N-((1-(3,5-difluorobenzyl)cyclobutyl)methyl)-6-oxo-1,6-dihydropyridazine-3-carboxamide; N-((1-(3-fluorobenzyl)cyclobutyl)methyl)-6-oxo-1,6-dihydropyridazine-3-carboxamide; N-((1-(2,4-difluorobenzyl)cyclobutyl)methyl)-4H-1,2,4-triazole-3-carboxamide; 1-methyl-N-((1-(2-(methylthio)benzyl)cyclobutyl)methyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazole- 3-carboxamide; 1-methyl-N-((1-(3-(methylthio)benzyl)cyclobutyl)methyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazole- 3-carboxamide; N-(2-cyclopropyl-3-(2,4,6-trifluorophenyl)propyl)-6-oxo-1,6-dihydropyrimidine-2-carboxamide; N-((4-(2,4-difluorobenzyl)tetrahydro-2H-pyran-4-yl)methyl)-3-oxo-2,3-dihydroisoxazole-5- carboxamide; N-((4-(2,4-difluorobenzyl)tetrahydro-2H-pyran-4-yl)methyl)-6-oxo-1,6-dihydropyrimidine-2- carboxamide; N-((1-(2,4-difluorobenzyl)spiro[2.2]pentan-1-yl)methyl)-6-oxo-1,6-dihydropyrimidine-2- carboxamide; N-(2-cyclopropyl-3-(2,4-difluorophenyl)-2-methylpropyl)-6-oxo-1,6-dihydropyrimidine-2- carboxamide; N-((2S)-2-cyclopropyl-3-(2,4-difluorophenyl)butyl)-6-oxo-1,6-dihydropyrimidine-2- carboxamide; N-(2-cyclopropyl-3-(2,6-difluorophenyl)propyl)-6-oxo-1,6-dihydropyrimidine-2-carboxamide; N-(2-cyclopropyl-3-(4-fluorophenyl)propyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-(2-(2,4-difluorobenzyl)butyl)-6-oxo-1,6-dihydropyrimidine-2-carboxamide; N-(2-cyclopropyl-3-(2,4-difluorophenyl)propyl)-5-fluoro-6-oxo-1,6-dihydropyrimidine-2- carboxamide; N-(3-(2-chloro-4-fluorophenyl)-2-cyclopropylpropyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-((1-(2,4-difluorobenzyl)spiro[2.2]pentan-1-yl)methyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazole-3- carboxamide; N-(2-cyclopropyl-3-(2,4-difluorophenyl)propyl)-5-oxo-4,5-dihydro-1,2,4-triazine-3- carboxamide; N-(2-cyclopropyl-3-(2,4-difluorophenyl)butyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(2,4-difluorobenzyl)cyclobutyl)methyl)-5-oxo-4,5-dihydro-1,2,4-triazine-3-carboxamide; N-(2-(2,4-difluorobenzyl)-2-ethylbutyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(3,4-difluorobenzyl)cyclobutyl)methyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazole-3- carboxamide; N-(2-cyclopropyl-3-(3,4-difluorophenyl)propyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazole-3- carboxamide; N-(2-cyclopropyl-3-(2,4-difluorophenyl)propyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazole-3- carboxamide; N-((1-(2,4-difluorobenzyl)cyclobutyl)methyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazole-3- carboxamide; N-((1-(2,4-difluorobenzyl)cyclobutyl)methyl)-5-(methoxymethyl)-4H-1,2,4-triazole-3- carboxamide; N-(2-cyclopropyl-3-(2,5-difluorophenyl)propyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazole-3- carboxamide; N-(2-(2,4-difluorobenzyl)butyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazole-3-carboxamide; N-(2-cyclopropyl-3-(2,4-difluorophenyl)-2-methylpropyl)-1-methyl-5-oxo-4,5-dihydro-1H- 1,2,4-triazole-3-carboxamide; N-((1-(2,4-difluorobenzyl)cyclobutyl)methyl)-5-oxo-4,5-dihydro-1,3,4-oxadiazole-2- carboxamide; N-(2-cyclopropyl-3-(2,6-difluorophenyl)propyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole- 3-carboxamide; N-((1-(2,4-difluorobenzyl)-3-fluorocyclobutyl)methyl)-6-oxo-1,6-dihydropyrimidine-2- carboxamide; N-(2-(2,4-difluorobenzyl)-2-fluorobutyl)-6-oxo-1,6-dihydropyrimidine-2-carboxamide; N-(2-cyclopropyl-3-(4-fluorophenyl)-2-methylpropyl)-6-oxo-1,6-dihydropyrimidine-2- carboxamide; N-(2-cyclopropyl-3-(4-fluorophenyl)propyl)-6-oxo-1,6-dihydropyrimidine-2-carboxamide; 5-bromo-N-(2-cyclopropyl-3-(2,4-difluorophenyl)propyl)-6-oxo-1,6-dihydropyrimidine-2- carboxamide; N-(3-(2-chloro-4,6-difluorophenyl)-2-cyclopropylpropyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-(2-(2,4-difluorobenzyl)-4,4,4-trifluorobutyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-(3-(4-chloro-2-fluorophenyl)-2-cyclopropylpropyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; (N-(-3-(2,4-difluorobenzyl)pentan-2-yl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; (N-(-2-cyclopropyl-3-(2,4-difluorophenyl)butyl)-6-oxo-1,6-dihydropyrimidine-2-carboxamide; N-[2-cyclopropyl-2-methyl-3-(2,4,6-trifluorophenyl)propyl]-1-methyl-5-oxo-4H-1,2,4-triazole- 3-carboxamide; N-((2-(2,4-difluorobenzyl)tetrahydrofuran-2-yl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-((1-(2,4-difluorobenzyl)spiro[2.2]pentan-1-yl)methyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-((1-(2,4-difluorobenzyl)spiro[2.2]pentan-1-yl)methyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazole-3- carboxamide; N-((1-(2,4-difluorobenzyl)spiro[2.2]pentan-1-yl)methyl)-6-oxo-1,6-dihydropyrimidine-2- carboxamide; N-(-2-cyclopropyl-3-(2,4-difluorophenyl)butyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole- 3-carboxamide; N-(2-cyclopropyl-3-(2,4-difluorophenyl)-2-methylpropyl)-1-methyl-5-oxo-4,5-dihydro-1H- 1,2,4-triazole-3-carboxamide; N-(3-(2-chloro-4-fluorophenyl)-2-cyclopropylpropyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-(2-cyclopropyl-3-(2,4-difluorophenyl)-2-methylpropyl)-6-oxo-1,6-dihydropyrimidine-2- carboxamide; N-(2-(2,4-difluorobenzyl)-4,4,4-trifluorobutyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3- carboxamide; N-((1-(2,4-difluorobenzyl)-3-fluorocyclobutyl)methyl)-6-oxo-1,6-dihydropyrimidine-2- carboxamide; N-(2-cyclopropyl-3-(4-fluorophenyl)propyl)-6-oxo-1,6-dihydropyrimidine-2-carboxamide; N-(2-cyclopropyl-3-(4-fluorophenyl)-2-methylpropyl)-6-oxo-1,6-dihydropyrimidine-2- carboxamide; N-(3-(4-chloro-2-fluorophenyl)-2-cyclopropylpropyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4- triazole-3-carboxamide; N-(2-(2,4-difluorobenzyl)-2-fluorobutyl)-6-oxo-1,6-dihydropyrimidine-2-carboxamide; N-[2-cyclopropyl-3-(2,4-difluorophenyl)-2-methylpropyl]-5-fluoro-4-oxo-3H-pyrimidine-2- carboxamide; 5-chloro-N-[2-cyclopropyl-3-(2,4-difluorophenyl)-2-methylpropyl]-4-oxo-3H-pyrimidine-2- carboxamide; N-[2-cyclopropyl-3-(4-fluorophenyl)-2-methylpropyl]-5-fluoro-4-oxo-3H-pyrimidine-2- carboxamide; N-[2-cyclopropyl-3-(4-fluorophenyl)-2-methylpropyl]-5-fluoro-4-oxo-3H-pyrimidine-2- carboxamide; 5-Chloro-N-[2-cyclopropyl-3-(4-fluorophenyl)-2-methylpropyl]-4-oxo-3H-pyrimidine-2- carboxamide; N-(2-cyclopropyl-3-(2,4-difluorophenyl)-2-methylpropyl)-5-methyl-6-oxo-1,6- dihydropyrimidine-2-carboxamide; N-(2-cyclopropyl-3-(4-fluorophenyl)-2-methylpropyl)-5-methyl-6-oxo-1,6-dihydropyrimidine-2- carboxamide; N-(2-cyclopropyl-3-(2,4-difluorophenyl)-2-methylpropyl)-3-hydroxyisoxazole-5-carboxamide; N-(2-cyclopropyl-3-(4-fluorophenyl)-2-methylpropyl)-3-hydroxyisoxazole-5-carboxamide; N-(2-cyclopropyl-3-(2,4-difluorophenyl)-2-methylpropyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazole- 3-carboxamide; and N-(2-cyclopropyl-3-(4-fluorophenyl)-2-methylpropyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazole-3- carboxamide; or a salt and / or solvate of any one thereof. In another aspect, the present invention provides a substance of formula (VI): wherein: R1ais H or C1-4alkyl; R1bis H or C1-4alkyl; R2ais H, halo, C1-4alkyl or C1-4haloalkyl; R3ais H, halo or C1-4alkyl; R4ais H or C1-4alkyl; R5ais H, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C2-6alkenyl, C2- 6haloalkenyl, C0-6alkylene(C3-6cycloalkyl), C0-6alkylene(OH); or R4aand R5atogether with the carbon atom to which they are attached form a C3-6cycloalkyl wherein said cycloalkyl may be optionally substituted by one or more groups selected from C1-4alkyl, C1-4haloalkyl and halo; R6ais H, halo, C1-4alkyl, C1-4haloalkyl, C1-4alkoxy or C1-4haloalkoxy; x is 0, 1 or 2; AA is a phenyl or phenyl fused to C5-6cycloalkyl, wherein said phenyl or phenyl fused to C5-6cycloalkyl may be optionally substituted by one or more AA1; AA1is halo, C2-6alkynyl, C1-6alkyl C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C3-6cycloalkyl, CN, OH, NRqRr, or NHSO2Rt; Rqis H or C1-4alkyl; Rris H or C1-4alkyl; Rtis C1-4alkyl; BA is a monocyclic or bicyclic heterocycle or a monocyclic or bicyclic heteroaryl, wherein said heterocycle or heteroaryl may be optionally substituted by one or more B1A; and B1Ais halo, C1-6alkyl, C1-6haloalkyl, oxo (=O), C1-6alkoxy, C1-6haloalkoxy, or C0-6alkylene(OH);or a salt and / or solvate thereof for use in the prevention or treatment of a disease, disorder,or condition which is an Other NLRX1-Related Disease, Disorder or Condition. Suitable substances of formula (VI), and compositions containing them, and processes for preparing them, are further described in PCT / GB2024 / 050145, which is herein incorporated by reference in its entirety. It will be understood that suitable and / or preferred substances of formula (VI) may include any of the substances (generic or specific) disclosed in PCT / GB2024 / 050145.Suitably, the present invention provides a substance of formula (VIB) for use according tothe present invention: wherein: R1ais H or C1-4alkyl; R1bis H or C1-4alkyl; R2ais H, halo, C1-4alkyl or C1-4haloalkyl; R3ais H, halo or C1-4alkyl; R4ais H or C1-4alkyl; R5ais H, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C2-6alkenyl, C2-6haloalkenyl, C0-6alkylene(C3-6cycloalkyl), C0-6alkylene(OH); or R4aand R5atogether with the atom to which they are attached form a C3-6cycloalkyl wherein said cycloalkyl may be optionally substituted by one or more groups selected from C1-4alkyl, C1-4haloalkyl and halo; R6ais H, halo, C1-4alkyl, C1-4haloalkyl, C1-4alkoxy or C1-4haloalkoxy; x is 0, 1 or 2; AA is a phenyl or phenyl fused to C5-6cycloalkyl optionally substituted by one or more AA1; AA1is halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C3-6cycloalkyl, CN, OH, NRqRr, or NHSO2Rt; Rqis H or C1-4alkyl; Rris H or C1-4alkyl; Rtis C1-4alkyl; BA is a monocyclic or bicyclic heterocycle or a monocyclic or bicyclic heteroaryl which may be optionally substituted by one or more B1A; and B1Ais halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, or C0-6alkylene(OH); or a salt and / or solvate thereof. In one aspect of the present invention, there is provided a substance of formula (VI) or (VIB), for use according to the present invention, wherein R1aand R1bare each H. Moreover, suitably, the present invention provides a substance of formula (VI) or (VIB), for use according to the present invention, wherein R2aand R3aare each H. Furthermore, suitably, the present invention provides a substance of formula (VI) or (VIB), for use according to the present invention, wherein R4aand R5atogether with the atom to which they are attachedform a C3-6cycloalkyl, such as cyclobutyl. In an alternative suitable aspect, the presentinvention provides a substance of formula (VI) or (VIB), for use according to the present invention, wherein R4aand R5aare each methyl. In addition, in one aspect of the present invention, there is provided a substance of formula (VI) or (VIB), wherein, suitably, R6ais H. In one aspect of the present invention, there is provided a substance of formula (VI) or (VIB), for use according to the present invention, wherein x is 1.Suitably, the present invention provides a substance of formula (VI) or (VIB), for useaccording to the present invention, wherein AA is phenyl. Furthermore, suitably, the presentinvention provides a substance of formula (VI) or (VIB), for use according to the presentinvention, wherein AA is substituted by one or more AA1, and wherein at least one AA1 ishalo. Suitably, the present invention provides a substance of formula (VI) or (VIB), for use according to the present invention, wherein BA is selected from the group consisting of: wherein: B1Bis H or C1-6alkyl, such as methyl; B2Bis H or C1-6alkyl, such as methyl; and B2Bis C0-6alkylene(OH), such as OH. For example, in one aspect of the invention, the present invention provides a substance offormula (VI) or (VIB), for use according to the present invention, wherein the substance offormula (VI) or (VIB) is selected from the group consisting of: (6-hydroxypyrazin-2-yl)(8-phenyl-6-azaspiro[3.4]octan-6-yl)methanone; (4-hydroxypyridin-2-yl)(8-phenyl-6-azaspiro[3.4]octan-6-yl)methanone; (3,3-dimethyl-4-phenylpyrrolidin-1-yl)(5-hydroxypyridin-3-yl)methanone; 2-methyl-5-(8-phenyl-6-azaspiro[3.4]octane-6-carbonyl)-2,4-dihydro-3H-1,2,4-triazol-3-one; (6-hydroxypyrazin-2-yl)(8-phenyl-6-azaspiro[3.4]octan-6-yl)methanone; 6-(8-(2-fluorophenyl)-6-azaspiro[3.4]octane-6-carbonyl)pyrazin-2(1H)-one; 6-(3,3-dimethyl-4-phenylpyrrolidine-1-carbonyl)pyrazin-2(1H)-one; 6-(3,3-dimethyl-4-phenylpiperidine-1-carbonyl)pyrazin-2(1H)-one; 6-(3,3-dimethyl-4-phenylpyrrolidine-1-carbonyl)pyrazin-2(1H)-one; 5-(8-(2-fluorophenyl)-6-azaspiro[3.4]octane-6-carbonyl)-2-methyl-2,4-dihydro-3H-1,2,4- triazol-3-one; 6-(3-methyl-4-phenylpyrrolidine-1-carbonyl)pyrazin-2(1H)-one; 8-Phenyl-6-(3H-1,2,3-triazole-4-carbonyl)-6-azaspiro[3.4]octane; 6-(3-ethyl-4-phenylpyrrolidine-1-carbonyl)pyrazin-2(1H)-one; 6-[8-(4-Chlorophenyl)-6-azaspiro[3.4]octane-6-carbonyl]-1H-pyrazin-2-one; 6-[4-Phenyl-2-azaspiro[4.4]nonane-2-carbonyl]-1H-pyrazin-2-one; rac-2-{8-phenyl-6-azaspiro[3.4]octane-6-carbonyl}-3H-pyrimidin-4-one; 6-[(4-Ethynylphenyl)-6-azaspiro[3.4]octane-6-carbonyl]-1H-pyrazin-2-one; 4-[6-(6-oxo-1H-pyrazine-2-carbonyl)-6-azaspiro[3.4]octan-8-yl]benzonitrile; 2-[8-phenyl-6-azaspiro[3.4]octane-6-carbonyl]-3H-pyrimidin-4-one; (3-hydroxyisoxazol-5-yl)(8-phenyl-6-azaspiro[3.4]octan-6-yl)methanone; (3-hydroxyisoxazol-5-yl)(8-phenyl-6-azaspiro[3.4]octan-6-yl)methanone; 3-[8-Phenyl-6-azaspiro[3.4]octane-6-carbonyl]-4H-1,2,4-oxadiazol-5-one; 2-(2-fluoro-8-phenyl-6-azaspiro[3.4]octane-6-carbonyl)pyrimidin-4(3H)-one; 6-(8-phenyl-6-azaspiro[3.4]octane-6-carbonyl)pyridin-2(1H)-one; 6-(8-phenyl-6-azaspiro[3.4]octane-6-carbonyl)pyrimidin-2(1H)-one; 6-(8-(4-methoxyphenyl)-6-azaspiro[3.4]octane-6-carbonyl)pyrazin-2(1H)-one; 6-(8-(4-bromophenyl)-6-azaspiro[3.4]octane-6-carbonyl)pyrazin-2(1H)-one; 6-(8-(2-chlorophenyl)-6-azaspiro[3.4]octane-6-carbonyl)pyrazin-2(1H)-one; 6-(8-(3-chlorophenyl)-6-azaspiro[3.4]octane-6-carbonyl)pyrazin-2(1H)-one; 6-8-(5-chloro-2-fluorophenyl)-6-azaspiro[3.4]octane-6-carbonyl)pyrazin-2(1H)-one; 6-(8-(3-chloro-2-fluorophenyl)-6-azaspiro[3.4]octane-6-carbonyl)pyrazin-2(1H)-one; 3-(8-phenyl-6-azaspiro[3.4]octane-6-carbonyl)-1,2,4-oxadiazol-5(4H)-one; 6-(8-(4-fluorophenyl)-6-azaspiro[3.4]octane-6-carbonyl)pyrazin-2(1H)-one; (8-(4-fluorophenyl)-6-azaspiro[3.4]octan-6-yl)(3-hydroxyisoxazol-5-yl)methanone; 6-(8-(2,4-difluorophenyl)-6-azaspiro[3.4]octane-6-carbonyl)pyrazin-2(1H)-one; (8-(3-fluorophenyl)-6-azaspiro[3.4]octan-6-yl)(3-hydroxyisoxazol-5-yl)methanone; (8-(2,3-difluorophenyl)-6-azaspiro[3.4]octan-6-yl)(3-hydroxyisoxazol-5-yl)methanone; 6-(8-(3-fluorophenyl)-6-azaspiro[3.4]octane-6-carbonyl)pyrazin-2(1H)-one; 3-(8-(4-fluorophenyl)-6-azaspiro[3.4]octane-6-carbonyl)-1,2,4-oxadiazol-5(4H)-one; (8-(2,4-difluorophenyl)-6-azaspiro[3.4]octan-6-yl)(3-hydroxyisoxazol-5-yl)methanone; 6-(8-(2,3-difluorophenyl)-6-azaspiro[3.4]octane-6-carbonyl)pyrazin-2(1H)-one; 3-(8-(2,3-difluorophenyl)-6-azaspiro[3.4]octane-6-carbonyl)-1,2,4-oxadiazol-5(4H)-one 6-(8-(3,4-difluorophenyl)-6-azaspiro[3.4]octane-6-carbonyl)pyrazin-2(1H)-one; (8-(3,4-difluorophenyl)-6-azaspiro[3.4]octan-6-yl)(3-hydroxyisoxazol-5-yl)methanone; 3-(8-(3,4-difluorophenyl)-6-azaspiro[3.4]octane-6-carbonyl)-1,2,4-oxadiazol-5(4H)-one; 3-(8-(2,4-difluorophenyl)-6-azaspiro[3.4]octane-6-carbonyl)-1,2,4-oxadiazol-5(4H)-one; and 3-(8-(3-fluorophenyl)-6-azaspiro[3.4]octane-6-carbonyl)-1,2,4-oxadiazol-5(4H)-one; or a salt and / or solvate of any one thereof.Compounds of formula (I), (II), (III), (IV), (V), (VA), (VI) and (VIB) may be used in the form ofsingle enantiomers or mixtures of enantiomers, such as racemic mixtures. In another aspect of the present invention, there is provided a method for preventing or treating a disease, disorder, or condition which is an Other NLRX1-Related Disease, Disorder or Condition, comprising administering to a subject in need thereof a prophylactically or therapeutically effective amount of a known inhibitor of mPTP activity. Suitably, the knowninhibitor of mPTP activity is a substance of formula (I), (II), (III), (IV), (V), (VA), (VI), or (VIB),as described above.In a further aspect of the present invention, there is provided the use of a known inhibitor of mPTP activity in the manufacture of a medicament for preventing or treating a disease, disorder, or condition which is an Other NLRX1-Related Disease, Disorder or Condition.Suitably, the known inhibitor of mPTP activity is a substance of formula (I), (II), (III), (IV), (V),(VA), (VI), or (VIB), as described above.Pharmaceutical Compositions and Administration RoutesSuitably a substance which is (i) capable of binding to NLRX1 and (ii) capable of inhibiting theactivity of the mPTP, and in particular (i) binds NLRX1 and (ii) inhibits the activity of the mPTP, and which is suitably identified by a method according to the present invention, for example a method described under the sub-heading ‘Methods for Identifying Substances for use according to the present invention’, for use in the treatment of a disease, disorder or condition associated with altered NLRX1 activity, is formulated as part of a pharmaceutical composition. Moreover, and similarly, suitably a known inhibitor of mPTP activity, in particular a substanceof formula (I), (II), (III), (IV), (V), (VA), (VI) or (VIB) for use in the treatment of a disease,disorder or condition which is an Other NLRX1-Related Disease, Disorder or Condition, is formulated as part of a pharmaceutical composition. Therefore, in one aspect the present invention provides a pharmaceutical compositioncomprising a substance which is (i) capable of binding to NLRX1 and (ii) capable of inhibitingthe activity of the mPTP, and in particular (i) binds NLRX1 and (ii) inhibits the activity of the mPTP, and one or more pharmaceutically acceptable excipients. Said pharmaceutical composition is suitably for use in the treatment of a disease, disorder or condition associated with altered NLRX1 activity. Furthermore, in another aspect, the present invention provides a pharmaceutical compositioncomprising a substance of formula (I), (II), (III), (IV), (V), (VA), (VI), or (VIB), and one or morepharmaceutically acceptable excipients. Said pharmaceutical composition is suitably for use in the treatment of a disease, disorder or condition which is an Other NLRX1-Related Disease, Disorder or Condition. The present invention also provides a method for preventing or treating a disease, disorder, or condition associated with altered NLRX1 activity, comprising administering to a subject in need thereof a prophylactically or therapeutically effective amount of a pharmaceutical composition comprising a substance which is (i) capable of binding to NLRX1 and (ii) capable of inhibiting the activity of the mPTP, and in particular (i) binds NLRX1 and (ii) inhibits the activity of the mPTP, and one or more pharmaceutically acceptable excipients. Furthermore, the present invention provides use of a pharmaceutical composition comprising a substance which is (i) capable of binding to NLRX1 and (ii) capable of inhibiting the activityof the mPTP, and in particular (i) binds NLRX1 and (ii) inhibits the activity of the mPTP, andone or more pharmaceutically acceptable excipients, in the manufacture of a medicament for preventing or treating a disease, disorder, or condition associated with altered NLRX1 activity. In addition, the present invention also provides a method for preventing or treating a disease, disorder or condition which is an Other NLRX1-Related Disease, Disorder or Condition,comprising administering to a subject in need thereof a prophylactically or therapeuticallyeffective amount of a pharmaceutical composition comprising a substance of formula (I), (II),(III), (IV), (V), (VA), (VI) or (VIB), and one or more pharmaceutically acceptable excipients.Moreover, the present invention provides use of a pharmaceutical composition comprising asubstance of formula (I), (II), (III), (IV), (V), (VA), (VI), or (VIB), and one or morepharmaceutically acceptable excipients, in the manufacture of a medicament for preventing or treating a disease, disorder, or condition which is an Other NLRX1-Related Disease, Disorder or Condition. For example, the pharmaceutical composition may comprise one or more pharmaceutically acceptable excipients selected from the group consisting of adjuvants, antioxidants,bacteriostats, binders, detergents, diluents, disintegrants, emulsifiers, extenders, lubricants,salts, solvents, solutes, stabilisers, sugars, suspending agents, surfactants, such as non-ionic surfactants, oils, preservatives, thickeners, tonicity adjusting (osmotic) agents, buffers, viscosity enhancers, and water.In any of the above aspects of the invention, the substances of the invention, includingsubstances of formula (I), (II), (III), (IV), (V), (VA), (VI), and (VIB), may be provided in theform of a pharmaceutically acceptable salt and / or solvate thereof. In particular, said substance may be provided in the form of a pharmaceutically acceptable salt and / or solvate, such as a pharmaceutically acceptable salt. It will be appreciated that for use in medicine the salts of the substances of the presentinvention, including substances of formula (I), (II), (III), (IV), (V), (VA), (VI), and (VIB), shouldbe pharmaceutically acceptable. Non-pharmaceutically acceptable salts of the said substances may be of use in other contexts such as during preparation of the substances of the invention. Suitable pharmaceutically acceptable salts will be apparent to those skilled inthe art. Pharmaceutically acceptable salts include those described by Berge et al. (1977).Such pharmaceutically acceptable salts include acid and base addition salts. Pharmaceutically acceptable acid additional salts may be formed with inorganic acids e.g. hydrochloric, hydrobromic, sulphuric, nitric or phosphoric acid and organic acids e.g. succinic, maleic, acetic, fumaric, citric, tartaric, benzoic, p-toluenesulfonic, methanesulfonic or naphthalenesulfonic acid. Other salts e.g. oxalates or formates, may be used, forexample in the isolation of substances of the invention and are included within the scope ofthis invention. Certain substances of the invention, including substances of formula (I), (II),(III), (IV), (V), (VA), (VI), and (VIB), may form acid or base addition salts with one or moreequivalents of the acid or base. The present invention includes within its scope all possible stoichiometric and non-stoichiometric forms.The substances of the present invention, including substances of formula (I), (II), (III), (IV),(V), (VA), (VI), and (VIB), may be prepared in crystalline or non-crystalline form and, ifcrystalline, may optionally be solvated, e.g. as the hydrate. This invention includes within itsscope stoichiometric solvates (e.g. hydrates) as well as substances containing variableamounts of solvent (e.g. water). The present disclosure includes all isotopic forms of the substances of the present invention,including substances of formula (I), (II), (III), (IV), (V), (VA), (VI), and (VIB), whether in a form(i) wherein all atoms of a given atomic number have a mass number (or mixture of mass numbers) which predominates in nature (referred to herein as the “natural isotopic form”) or (ii) wherein one or more atoms are replaced by atoms having the same atomic number, but a mass number different from the mass number of atoms which predominates in nature (referred to herein as an “unnatural variant isotopic form”). It is understood that an atom may naturally exist as a mixture of mass numbers. The term “unnatural variant isotopic form” also includes embodiments in which the proportion of an atom of given atomic number having a mass number found less commonly in nature (referred to herein as an “uncommon isotope”) has been increased relative to that which is naturally occurring e.g. to the level of >20%, >50%, >75%, >90%, >95% or >99% by number of the atoms of that atomic number (the latter embodiment referred to as an "isotopically enriched variant form"). The term “unnatural variant isotopic form” also includes embodiments in which the proportion of an uncommon isotope has been reduced relative tothat which is naturally occurring. Isotopic forms may include radioactive forms (i.e. theyincorporate radioisotopes) and non-radioactive forms. Radioactive forms will typically beisotopically enriched variant forms. An unnatural variant isotopic form of a compound maythus contain one or more artificial or uncommon isotopes such as deuterium (2H or D),carbon-11 (11C), carbon-13 (13C), carbon-14 (14C), nitrogen-13 (13N), nitrogen-15 (15N),oxygen-15 (15O), oxygen-17 (17O), oxygen-18 (18O), phosphorus-32 (32P), sulphur-35 (35S), chlorine-36 (36Cl), chlorine-37 (37Cl), fluorine-18 (18F) iodine-123 (123I), iodine-125 (125I) in one or more atoms or may contain an increased proportion of said isotopes as compared withthe proportion that predominates in nature in one or more atoms. Unnatural variant isotopicforms comprising radioisotopes may, for example, be used for drug and / or substrate tissue distribution studies. The radioactive isotopes tritium, i.e.3H, and carbon-14, i.e.14C, are particularly useful for this purpose in view of their ease of incorporation and ready means of detection. Unnatural variant isotopic forms which incorporate deuterium i.e.2H or D may afford certain therapeutic advantages resulting from greater metabolic stability, for example,increased in vivo half-life or reduced dosage requirements, and hence may be preferred insome circumstances. Further, unnatural variant isotopic forms may be prepared whichincorporate positron emitting isotopes, such as11C,18F,15O and13N, and would be useful in Positron Emission Topography (PET) studies for examining substrate receptor occupancy.In one embodiment, the substances of the present invention, including substances offormula (I), (II), (III), (IV), (V), (VA), (VI), and (VIB), are provided in a natural isotopic form.In one embodiment, the substances of the present invention, including substances offormula (I), (II), (III), (IV), (V), (VA), (VI), and (VIB), are provided in an unnatural variantisotopic form. In a specific embodiment, the unnatural variant isotopic form is a form in which deuterium (i.e.2H or D) is incorporated where hydrogen is specified in the chemicalstructure in one or more atoms of a substance of the invention. In one embodiment, theatoms of the substances of the invention are in an isotopic form which is not radioactive. Inone embodiment, one or more atoms of the substances of the invention are in an isotopicform which is radioactive. Suitably radioactive isotopes are stable isotopes. Suitably theunnatural variant isotopic form is a pharmaceutically acceptable form.In one embodiment, substances of the present invention, including substances of formula (I),(II), (III), (IV), (V), (VA), (VI), and (VIB), are provided whereby a single atom of the compoundexists in an unnatural variant isotopic form. In another embodiment, substances of thepresent invention, including substances of formula (I), (II), (III), (IV), (V), (VA), (VI), and(VIB), two or more atoms exist in an unnatural variant isotopic form. Unnatural isotopic variant forms can generally be prepared by conventional techniques known to those skilled in the art or by processes described herein e.g. processes analogous to those described inthe accompanying Examples for preparing natural isotopic forms. Thus, unnatural isotopicvariant forms could be prepared by using appropriate isotopically variant (or labelled) reagents in place of the normal reagents employed in the Examples.Since the substances of the invention are intended for use in pharmaceutical compositions itwill readily be understood that they are each preferably provided in substantially pure form, for example at least 60% pure, more suitably at least 75% pure and preferably at least 85%,especially at least 98% pure (% are on a weight for weight basis). Impure preparations of thesubstances of the invention may be used for preparing the more pure forms used in thepharmaceutical compositions. The amount of active ingredient which is required to achieve a prophylactic or therapeutic effect will, of course, vary with the particular substance, the route of administration, the subject under treatment or prophylaxis, including the type, species, age, weight, sex, and medical condition of the subject and the renal and hepatic function of the subject; and the particular disease, disorder, or condition being treated or prevented, as well as its severity. An ordinarily skilled physician, veterinarian or clinician can readily determine and prescribe the effective amount of the drug required to prevent, counter or arrest the progress of the disease, disorder, or condition. The pharmaceutical compositions according to the present invention include those suitable for oral, parenteral (including subcutaneous, intradermal, intramuscular, intravenous [bolus or infusion], and intraarticular), intranasal (also known as nasal administration), inhalation (including fine particle dusts or mists which may be generated by means of various types of metered dose pressurized aerosols, nebulizers or insufflators) insufflation, rectal, intraperitoneal, topical (including dermal, buccal, sublingual, and intraocular) and intrathecal administration, although the most suitable route may depend upon, for example, the disease,disorder, or condition of the subject. In particular, suitable pharmaceutical compositionsaccording to the present invention are those suitable for oral, intrathecal and parenteral administration; and more suitably are those suitable for oral or intrathecal administration. Suitably, pharmaceutical compositions of the present invention may be administered in a single daily dose, or the total daily dosage may be administered in divided doses of two, three or four times daily. Oral dosages of the present invention, when used for the indicated effects, will range between about 0.01 mg per kg of body weight per day (mg / kg / day) to about 100 mg / kg / day, suitably 0.01 mg per kg of body weight per day (mg / kg / day) to 10 mg / kg / day, and most suitably 0.1 to 5.0 mg / kg / day, for adult humans. For oral administration, the compositions are suitably provided in the form of tablets or other forms of presentation provided in discrete units, suchas capsules, cachets, pills, containing 0.01, 0.05, 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 15.0, 25.0, 50.0,100, and 500 milligrams of the active ingredient for the symptomatic adjustment of the dosageto the subject to be treated. Alternatively, the oral composition may be presented as a powderor granules; as a solution or a suspension in an aqueous liquid or a non-aqueous liquid, for example as elixirs, tinctures, suspensions or syrups; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion. The active ingredient may also be presented as a bolus, electuaryor paste. An oral composition typically contains from about 0.01 mg to about 500 mg of theactive ingredient, suitably from about 1 mg to about 100 mg of active ingredient.The oral dosages of the present invention may conveniently be presented in unit dosage formand may be prepared by any of the methods well known in the art of pharmacy. All methods include the step of bringing the active ingredient into association with one or morepharmaceutically acceptable carriers. In general, the compositions are prepared by uniformlyand intimately bringing into association the active ingredient with liquid carriers or finely divided solid carriers or both and then, if necessary, shaping the product into the desired nit. A tablet may be made by compression or moulding, optionally with one or more pharmaceutically acceptable carriers. Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as a powder or granules, optionally mixed with a binder, lubricant, inert diluent, lubricating, surface active or dispersing agent. Moulded tablets may be made by moulding in a suitable machine a mixture of thepowdered substance moistened with an inert liquid diluent. The tablets may optionally be coated or scored and may be formulated so as to provide slow or controlled release of the active ingredient therein. The pharmaceutical compositions therefore may be administered in a form suitable for immediate release or extended release. Immediate release or extended release can be achieved by the use of suitable pharmaceutical compositions comprising a substance of the present invention, or, particularly in the case of extended release, by the use of devices such as subcutaneous implants or osmotic pumps. The pharmaceuticalcompositions of the invention may also be administered liposomally.Exemplary pharmaceutical compositions for oral administration include suspensions which can contain, for example, microcrystalline cellulose for imparting bulk, alginic acid or sodium alginate as a suspending agent, methylcellulose as a viscosity enhancer, and sweeteners or flavoring agents such as those known in the art; and immediate release tablets which can contain, for example, microcrystalline cellulose, dicalcium phosphate, starch, magnesiumstearate, calcium sulfate, sorbitol, glucose and / or lactose and / or other excipients, binders,extenders, disintegrants, diluents and lubricants such as those known in the art. Suitable binders include starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tragacanth or sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes and the like. Disintegrators include without limitation starch, methylcellulose, agar, bentonite, xanthan gum and the like.Pharmaceutical compositions of the invention may also be administered via the oral cavityby sublingual and / or buccal administration. Pharmaceutical compositions for topical administration in the mouth, for example buccally or sublingually, include lozenges comprising the active ingredient in a flavoured basis such as sucrose and acacia or tragacanth, and pastilles comprising the active ingredient in a basis such as gelatin and glycerine or sucrose and acacia. Exemplary compositions for topical administration include atopical carrier such as Plastibase (mineral oil gelled with polyethylene). Molded tablets,compressed tablets or freeze-dried tablets are exemplary forms which may be used.Exemplary pharmaceutical compositions include those formulating a substance of thepresent invention with fast dissolving diluents such as mannitol, lactose, sucrose and / or cyclodextrins. Also included in such compositions may be high molecular weight excipientssuch as celluloses (avicel) or polyethylene glycols (PEG). Such compositions can alsoinclude an excipient to aid mucosal adhesion such as hydroxy propyl cellulose (HPC), hydroxy propyl methyl cellulose (HPMC), sodium carboxy methyl cellulose (SCMC), maleic anhydride copolymer (e.g., Gantrez), and agents to control release such as polyacrylic copolymer (e.g. Carbopol 934). Lubricants, glidants, flavors, coloring agents and stabilizers may also be added for ease of fabrication and use. Lubricants used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride and the like. For oral administration in liquid form, the oral drug components can be combined with any oral, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. Intrathecal administration involves injection of the pharmaceutical composition of the invention into the spinal canal, or into the subarachnoid space so that it reaches the cerebrospinal fluid. This is advantageous for the administration of substances which may not be able to pass the blood brain barrier via other routes of administration, such as oraladministration. Pharmaceutical compositions of the present invention may be administeredintrathecally by continuous infusion such as with a catheter, or a pump, or intrathecally by a single bolus injection or by intermittent bolus injection. Pharmaceutical compositions of the invention which are administered intrathecally and continuously, are suitably administered via implantable delivery devices, such as an implantable pump. Examples of such delivery devices include devices which can be implanted subcutaneously in the body or in the cranium, and provides an access port through which the pharmaceutical compositions maybe delivered to the nerves or brain. To be administered intrathecally, the pharmaceuticalcomposition may also be administered intermittently. The intermittent administration may be, for example, every thirty minutes, every hour, every several hours, every 24 hours, every couple of days (for example every 48 or 72 hours) or any combination thereof. Intrathecal dosages of the present invention, when used for the indicated effects, will typically be less than 1 mg, such as less than 500 µg, for example less than 250 µg per kg of body weight when administered in a single dose or intermittently for adult humans. When administered continuously, the intrathecal dosages of the present invention will typically be less than 250 µg per kg body weight per hour, such as less than 125 µg per kg body weight per hour for adult humans.Pharmaceutical compositions for parenteral administration include aqueous and non-aqueoussterile injection solutions which may contain antioxidants, buffers, bacteriostats and soluteswhich render the composition isotonic with the blood of the intended recipient; and aqueousand non-aqueous sterile suspensions which may include suspending agents and thickeningagents. The pharmaceutical compositions may be presented in unit-dose or multi-dosecontainers, for example sealed ampoules and vials, and may be stored in a freeze-dried (lyophilised) condition requiring only the addition of the sterile liquid carrier, for example saline or water-for-injection, immediately prior to use. Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules and tablets of the kind previously described. Exemplary pharmaceutical compositions for parenteral administration include injectable solutions or suspensions which can contain, for example, suitable non-toxic, parenterally acceptable diluents or solvents, such as mannitol, 1,3-butanediol, water, Ringer’s solution, an isotonic sodium chloride solution, or other suitable dispersing or wetting andsuspending agents, including synthetic mono- or diglycerides, and fatty acids, including oleicacid, or Cremaphor. Intravenously, the most suitable doses will range from about 0.1 to about10 mg / kg / minute during a constant rate infusion.In an alternative suitable aspect, a pharmaceutical composition of the invention isadministered by intranasal, inhalation (including fine particle dusts or mists which may be generated by means of various types of metered dose pressurized aerosols, nebulizers or insufflators) or insufflation administration. Such a method of administration allows for lowdoses of the pharmaceutical composition of the invention to be administered, which can leadto a reduction in side-effects. Exemplary pharmaceutical compositions for intranasal, aerosolor inhalation administration include solutions in saline, which can contain, for example,benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, and / or other solubilizing or dispersing agents such as those known in the art.For example, a daily dose of 10 to 0.01µg, suitably 1 to 0.01µg, and more suitably in theregion of as low as 0.1µg (100ng) of active ingredient may be used. Suitably pharmaceuticalcompositions of the invention can be administered in intranasal form via topical use ofsuitable intranasal vehicles, or via transdermal routes, using those forms of transdermal skin patches well known to those of ordinary skill in the art. To be administered in the form of a transdermal delivery system, the dosage administration will, of course, be continuous rather than intermittent throughout the dosage regimen. Pharmaceutical compositions for rectal administration may be presented as a suppository with the usual carriers such as cocoa butter, synthetic glyceride esters or polyethylene glycol. Such carriers are typically solid at ordinary temperatures but liquefy and / or dissolve in the rectal cavity to release the drug. Examples General Methods The substances used in the Examples below, including the Background Probes and Test Substances, are disclosed in, or may suitably be prepared according to the methods disclosed in WO2022 / 049376, and / or WO2022 / 049377, and / or WO2023 / 166303, and / or WO2024 / 153945, and / or WO2024 / 153946, and / or WO2025 / 052129.Assay for inhibition of mPTP activity - Rat liver mitochondria assayPharmacological inhibition or modulation of the mPTP can be measured in well characterised ‘Ca2+retention’ assays performed in isolated mitochondria. In vitro, isolated mitochondria rapidly sequester exogenous Ca2+until the intramitochondrial Ca2+concentration reaches the threshold for mPTP activation. Once the pore is activated, mitochondrial integrity iscompromised and the stored Ca2+ is released. The distribution of Ca2+ between extra- andintra-mitochondrial compartments can be measured in real time with the use of membrane-impermeant Ca2+sensitive fluorescent dyes. Depending on the configuration of the assay, inhibition or modulation of the mPTP either delays the opening of the pore or increases the concentration of Ca2+required to induce mPTP opening. mPTP activity is measured in mitochondria freshly isolated from female Sprague Dawley (250 to 300 gram) rat livers using the folllowing method. Cervical dislocation is performed on therat. The liver is then perfused in-situ with ~40 ml cold Dulbecco’s Phosphate Buffered Saline(DPBS) prior to dissection and transfered into 30 ml Isolation Buffer (250mM Sucrose, 10mMKCl, 1mM EGTA, 1mM EDTA, 25mM HEPES, adjusted to pH 7.5 with 1M NaOH). Each lobe of the liver is then removed from the buffer, minced using tweezers and a scalpel into ~5mm pieces then transferred into a 50 ml Potterton dounce homogenization tube on ice containing 30 ml ice-cold centrifugation buffer (300mM Trehalose, 25mM HEPES, 1mM EGTA, 1mM EDTA, 10mM KCl, adjusted to pH 7.5 with 1M NaOH and supplemented with 0.1% bovine serum albumin (BSA) and complete protease inhibitor cocktail (one tablet of inhibitor per 50mls of buffer). Homogenisation is carried out using a teflon pestle at 1800 rpm. The slurry is centrifuged at 800 g for 10 min at 4oC, then the supernatant centrifuged at 10,000 g for 10 min. The pellet is washed once with FLIPR assay buffer (75mM Mannitol, 25mM Sucrose, 5mM Potassium Phosphate Monobasic, 20mM Tris base, 100mM KCl, 0.1 % BSA adjusted to pH 7.4 with 5M HCl) centrifuged again, then resuspended in FLIPR assay buffer to aconcentration of 8.8 mg / ml protein. Tested compounds (10 mM stock in DMSO) are seriallydiluted in DMSO in half log steps to generate 10 test concentrations (final concentrations in assay 30 µM to 1 nM). An intermediate dilution of 5 µl DMSO samples into 247 µl FLIPR assay buffer is carried out prior to transfer of 5 µl into duplicate wells of a 384 well polypropyleneassay plate. Control wells are 0.5 % (v / v) DMSO and 5 µM cyclosporin A.A stock mitochondria / Fluo5N assay solution is prepared in 5.6 ml FLIPR assay buffer (at RT) supplemented with succinate disodium salt (10mM), rotenone (1µM), Fluo5N pentapotassium salt (2 µM) and 1 ml mitochondria suspension, then transferred (15 µl) into the assay plate containing test compounds and incubated for 10 min at RT. Assay plates are processed for fluorescence detection on either a FLIPR Tetra (Molecular Devices) or CLARIOstar (BMG) plate reader. For kinetic fluorescence detection on the FLIPR, dye fluorescence is measured every 3 sec for a total of 10 min. After 12 sec, a 2.5 µl bolus of CaCl2(75 µM) is added from a source plate containing 675 µM CaCl2in FLIPR assay buffer. Alternatively, the 2.5 µl addition of CaCl2is performed using a Viaflow 384, plates areincubated at RT for 10 min, and dyefluorescence measured after 10 min on the CLARIOstar plate reader. pIC50 values for testedcompounds are calculated using the fluorescence value collected at the 10 min timepoint oneither plate reader, with % inhibition calculated using the DMSO control and cyclosporin A values as 0 and 100 % respectively.Assay for inhibition of mPTP activity - Rat brain mitochondria assaymPTP activity is measured in brain mitochondria freshly isolated from female Sprague Dawley (250 to 300 gram) rats. Anaesthetised rats were perfused in-situ with ~40 ml cold Dulbecco’s Phosphate Buffered Saline (DPBS), then brains dissected and transferred into 30 ml Isolation Buffer (225mM mannitol, 75 mM sucrose, 1mM EGTA, adjusted to pH 7.4 with 1M NaOH).The brain is minced using tweezers and a scalpel into ~5mm pieces then transferred into a 50ml Potterton Dounce homogenization tube on ice containing 10 ml ice-cold isolation buffer (as above with addition of Complete Protease inhibitor; 1 tablet per 50 ml buffer). Homogenisationis carried out using a teflon pestle at 1800 rpm. The slurry is centrifuged at 2000 g for 10 minat 4oC, then the supernatant centrifuged at 12,000 g for 9 min. The pellet is resuspended with a dounce homogeniser in isolation buffer as above but with the addition of 0.02 % digitonin, centrifuged at 12,000g for 11 min and finally resuspended in 5 ml modified isolation buffer (asabove but with EGTA reduced to 0.1 mM).Test compounds are prepared in 384 well polypropylene assay plates as described above forthe liver mitochondria assay. A stock mitochondria / Fluo5N assay solution is prepared in 5.6 ml assay buffer (120 mM mannitol, 40 mM MOPS, 5 mM KH2PO4, 60 mM KCl, 10 mM pyruvate, 2 mM malate, 2 mM MgCl2, 20 µM ADP, 1.26 µM oligomycin A, adjusted to pH 7.4) supplemented with Fluo5N pentapotassium salt (2 µM) and 1 ml mitochondria suspension, then transferred (15 µl) into the assay plate containing test compounds and incubated for 10min at RT. Assay plates are then transferred to a FLIPR Tetra plate reader (MolecularDevices). Dye fluorescence is then measured every 3 sec for a total of 10 min. After 12 sec,a 2.5 µl bolus of Ca2+ (75 µM) is added from a source plate containing 675 µM CaCl2 in FLIPRassay buffer. pIC50 values for test compounds are calculated using the fluorescence value collected at the 10 min timepoint with % inhibition calculated using the DMSO control and cyclosporin A values at 100 % and 0 % respectively. Background Examples Background Example 1: Identification of NLRX1 as a binding partner of inhibitors of the mPTP Potential binding partners of known inhibitors of the mPTP were identified by a process of affinity-based chemoproteomics, using Background Probe 1 below: which is known to be a potent inhibitor of the mPTP. Moreover, Background Probe 1 is suitable for immobilization on azide-activated affinity resin. Conjugation of Background Probe 1 to azide-agarose beads were carried out by click chemistry using two different coupling densities, specifically 0.6 mM and 1.2 mM, to yield low- density (LD) and high-density (HD) beads respectively.Affinity-based purification of target proteins to be screened was performed in clarifieddetergent cell lysates, specifically containing 1 mg / mL protein in 0.5% Triton X-100 extract, prepared from HEK293 cells. In a first experiment, control beads (i.e. empty azide-agarose beads), LD beads, and HD beads, were incubated in duplicate with the clarified detergent cell lysates referred to above, and in the presence of DMSO control, or Background Probe 2 below: at a concentration of 1 µM or 30 µM, each in 0.3% DMSO, at 4oC. Background Probe 2 is another known inhibitor of the mPTP, and in particular is known to be a far more potent inhibitor of the mPTP than Background Probe 1 above. Therefore, incubation with Background Probe 2 is expected to displace proteins bound to Background Probe 1 on LD and HD beads. After incubation, beads were collected via centrifugation and washed according to standard protocol. Co-purified proteins were subsequently digested on the bead using trypsin, and the resultant peptides were identified by liquid chromatography / mass spectrometry (LC / MS).In total 5062 proteins were identified across all samples. The following criteria were applied tofilter this protein set and identify only those proteins which demonstrated specific binding toBackground Probe 1:(i) The protein / peptide should be identified in both replicate samples (i.e. BackgroundProbe 1 beads in the presence of DMSO);(ii) The protein / peptide should be enriched by more than 5-fold in Background Probe 1bead samples relative to control (empty) bead samples;(iii) The protein should be displaced by Background Probe 2 by greater than 30%;(iv) Displacement by 30 µM Background Probe 2 should be greater than displacement by1 µM Background Probe 2;(v) The criteria of points (ii), (iii), and (iv) above should apply to both replicate samples;and(vi) The protein / peptide should be identified in both LD and HD bead samples.The results of the application of the above criteria are shown in Figure 1. In particular, proteinsidentified in accordance with the criteria above are plotted according to the % displacement value, which is itself the mean of duplicate values, of each of the LD and HD beads by Background Probe 2. The results show that only two proteins, PTDSS1 and NLRX1, are common, strong, hits between LD and HD beads. Of these two proteins, only NLRX1 is a mitochondrial protein. Furthermore, NLRX1 was the protein maximally displaced by Background Probe 2, relative to all other proteins identified as potential binding partners ofknown inhibitors of the mPTP. These findings implicate NLRX1 as a binding partner of knowninhibitors of the mPTP. In a second experiment, a repeat chemoproteomic screen was performed, with the addition of a further negative control. Specifically, conjugation of Background Probe 1 to azide-agarosebeads was carried out by click chemistry using a coupling density of 1 mM. Incubation ofBackground Probe 1 beads, or control (i.e. empty azide-agarose) beads, was performed in triplicate in the presence of either DMSO control, Background Probe 2 (at a concentration of 1 µM or 30 µM, in the presence of 0.3% DMSO), or the inactive control molecule, Background Control Probe 1: at a concentration of 1 µM or 30 µM, in the presence of 0.3% DMSO. Background ControlProbe 1, the enantiomer of Background Probe 2, is inactive as an inhibitor of the mPTP.Therefore, incubation with Background Control Probe 1 would not be expected to displaceproteins bound specifically to Background Probe 1 on LD and HD beads. Subsequently, thesame criteria as outlined above was used to filter the set of proteins identified by LC / MS, withthe two additional criteria below: (i) The protein / peptide should be identified in at least two of the three replicates (i.e. Background Probe 1 beads in the presence of DMSO); and(ii) Displacement by 30 µM Background Control Probe 1 should be less than 40%.Application of this amended criteria to the proteins identified by LC / MS following the second experiment resulted in only NLRX1 being identified. Whilst PTDSS1 was also enriched in thesecond experiment, it’s binding to Background Probe 1 beads was equally displaced by thepotent mPTP inhibitor Background Probe 2 and the inactive control, Background Control Prove 1, and therefore its binding was considered to be non-specific. A summary of the results of Background Example 1 are shown in Figure 2. In particular, proteins identified in the first experiment that were both (a) enriched by more than 5-fold in Background Probe 1 bead samples relative to control (empty) bead samples, and (b) displaced by greater than 0% by Background Probe 2, were plotted according to their % displacement by Background Probe 2 in both the first experiment (Exp1) and the second experiment (Exp2).The results show that only NLRX1 is enriched by more than 5-fold in Background Probe 1bead samples relative to control (empty) bead samples and displaced by greater than 60% inboth the first and second experiments. In fact, NLRX1 had a mean displacement of 93% across all samples. These results provide strong evidence to suggest that NLRX1 is a binding partner of known inhibitors of the mPTP. Background Example 2: Evaluation of the role of NLRX1 in interaction with, and modulation of, the mPTP The activity of the mPTP in both wild-type and NLRX1 knock-out (KO) cells was evaluatedusing methods known in the art and described in published protocols (see Kuznetsov et al.2008). In particular, wild-type and NLRX1 KO HeLa cells were purchased from a commercial provider (Abcam). Subsequently, both cell types were resuspended in digitonin lysis buffer (130 mM potassium chloride, 10 mM MOPS-Tris, 1mM Trizma-Pi, 1 mM EGTA, 100 µM digitonin) and incubated on ice for 5 minutes to ensure permeabilization of the plasma membrane). Following two centrifugation and wash steps (i.e. to remove the digitonin buffer) the cells were added to wells of a 96-well plate at a density of 1 x 106cells per well, in 200 µL assay buffer (130 mM potassium chloride, 10 mM MOPS-Tris, 1mM Trizma-Pi, 10 µM EGTA-Tris, 5 mM glutamate, 2.5 mM malate, 0.5 µM Calcium Green 5N, pH 7.4), with wells containing either test substanceor 0.1% DMSO control. The 96-well plate was then immediately transferred to a FLIPR® TetraPlate Reader for kinetic fluorescence detection. Calcium chloride, 5 µL of a 200 µM stock solution, was added to the plate every 5 minutes and fluorescence readings were collected every 3 seconds. To certain wells, known inhibitors of the mPTP, namely either cyclosporin A or Background Inhibitor 1 below: were added at a final concentration of 10 µM. The mean background-corrected fluorescencevalues for each condition were plotted against time. The results are shown in Figure 3.In wild-type cells, mitochondria displayed the expected response to sequential calcium chloride additions. Specifically, following the first four additions of calcium chloride, the mitochondria sequestered the Ca2+via active uptake resulting in the return of the Calcium Green 5N fluorescence to baseline. Following the fifth and sixth additions of calcium chloride, the fluorescence no longer returned to baseline but instead increased, indicative of mitochondrial permeability transition concomitant with loss of Ca2+retention. Both cyclosporin A and Background Inhibitor 1 prevented any pore transition throughout the time course of the assay. In NLRX1 KO cells, no obvious pore transition could be observed during the time course of the assay, in response to calcium chloride additions, indicating that mitochondria are dependent on NLRX1 for the formation of the calcium-dependent mPTP. Moreover, neither cyclosporin A nor Background Inhibitor 1 have any impact on the fluorescence profile. This is consistent with the mPTP already being fully inhibited by genetic deletion of NLRX1, on which the calcium-dependent mPTP appears to be dependent. In summary, these results suggest NLRX1 forms, or is a component of, the mPTP. NLRX1 Binding Examples In view of the Background Examples above, the present inventors have discovered thatinhibition of mPTP activity is mediated via binding to NLRX1. NLRX1 is therefore a novel targetagainst which substances may be screened for binding ability. The present inventors havetherefore developed novel methods and assays which are suitable for identifying substances which are capable of binding to NLRX1. NLRX1 Binding Example 1: Screening new substances for NLRX1 binding using a cellular thermal shift assay (CETSA) New substances may be screened for binding to NLRX1 using a cellular thermal shift assay (CETSA), the protocol for which has been developed and optimised by the present inventors. Specifically, HEK293T cells were suspended in Hanks’ balanced salt solution (HBSS; Gibco) at a concentration of 40 million cells / mL, prior to mixing in equal parts with test substances (suspended in HBSS supplemented with 0.4% DMSO) to yield a final cell density of 20 millioncells / mL in 0.2 % DMSO.Samples were then incubated for 60 minutes, at 37 °C, in tubes subjected to end-over-end rotation. Following incubation, samples are divided into 50 µL aliquots in PCR tubes beforebeing subjected to a 12-step heat challenge, between 53oC and 70°C, for 3 minutes on athermal cycler. This heating step was followed by cell lysis via three cycles of freeze-thaw,following the first cycle of which radioimmunoprecipitation assay buffer (RIPA buffer; Merck)was added to achieve a final concentration of RIPA buffer of 1 x and tubes incubated for 15min at 4 °C.Following cell lysis, the resultant precipitated proteins and cell debris were pelleted viacentrifugation at 20000 g for 20 minutes. After centrifugation, the supernatant of each sample,which contains the soluble protein fraction, was mixed with gel loading buffer (NuPAGETMLDSsample buffer and NuPAGETM sample reducing agent; ThermoFisher Scientific) to achieve afinal concentration of 1 x gel loading buffer, and the loaded sample was heated at 70oC for 10 minutes. The quantity of NLRX1 protein in each sample, of 10 µL volume, was quantified via WesternBlotting using an anti-NLRX1 mouse monoclonal antibody (#TA809764; OriGene).Subsequent chemiluminescent Western Blotting detection was achieved using a horseradishperoxidase (HRP) conjugated anti-mouse secondary antibody (W4021; Promega), at a dilutionof 1:20000, by incubation with the anti-NLRX1 antibody treated Westen Blot sample for 1 hourat room temperature, and subsequent incubation with Clarity Western ECL substrates (Bio- Rad), according to the manufacturer’s instructions. To quantify or determine the ability of substances to bind to NLRX1, Western Blot intensitieswere obtained by measuring the chemiluminescence counts per square mm (I = count / mm2).The obtained intensities at each temperature (Ix) were then plotted as the luminescence count, normalised to the value obtained at 53°C. The results of testing a known potent inhibitor of the mPTP, herein referred to as TestSubstance 1, via the above-described CETSA are shown in Figure 4. In particular, Figure 4shows that NLRX1 in control (DMSO) conditions demonstrated typical melting in the CETSA, i.e. a Tm of 61.0oC (i.e. midpoint value of melting temperature, mean of n = 5 replicates). In the presence of Test Substance 1, the Tm value shifted by 1.9oC to 62.9oC (mean of n = 5 replicates), which is consistent with direct binding of Test Substance 1 to NLRX1 and consequently stabilisation of NLRX1.Moreover, the results of testing a series of Test Substances in the above-described CETSAare shown in Figure 5. The structures of Test Substances 1 to 5 are shown in Table 1 below: Table 1: Test Substance No. StructureTest Substance 1Test Substance 2Test Substance 3Test Substance 4Test Substance 5Test Substance 1 is the same as Background Probe 2 referred to above. Substance 2 is thesame as Background Control Probe 1 referred to above. Test Substance 3 is the same asBackground Probe 1 referred to above.The results of Figure 5 show that the above-described CETSA protocol is a suitable methodfor the identification of substances which bind to NLRX1. In particular, Test Substances 1, 3, and 4, were demonstrated to bind to NLRX1 with different affinities. Test Substances 2 and 5 failed to demonstrate significant specific NLRX1 binding. EC50 values (of NLRX1 binding)were calculated for each of Test Substances 1, 3, and 4 and are provided in Table 2 below:Table 2: Test Substance No. Calculated EC50 Value (µM)*Test Substance 1 6Test Substance 3 34Test Substance 4 2*mean of 3 or more replicate experiments NLRX1 Binding Example 2: Screening new substances for NLRX1 binding using a filtration binding assay New substances may be screened for binding to NLRX1 using a filtration binding assay, the protocol for which has been developed and optimised by the present inventors. Specifically, NLRX1-expressing membranes were prepared from a HeLa cell line stably transfected with the full-length human NLRX1 gene. In particular, cultured cells were detached and suspended with Buffer A (50 mM Tris HCl pH 7.4, 5 mM EDTA / Tris pH 7.4,20 mM NaCl, 5 mM KCl, 5 mM MgCl2, 10 μg / ml trypsin inhibitor, 1 μg / ml of leupeptin, and 75μg / ml PMSF) at 4°C and at a density of 500 x 106 cells per 10 mL. Cells were then lysedusing an ultrasound probe for 1 minute. The homogenate obtained was adjusted to 40 mLBuffer A and centrifugated at 50000 g. The pellet was removed using a 23G gauge needlethen resuspended by agitation with a 25G gauge needle in Buffer B (Buffer A with 10%glycerol). Protein quantification was determined according to the Bradford method andaliquots were stored at -80°C. Subsequently, NLRX1-expressing membranes are suspended in incubation buffer (50 mMTris / HCl, 5 mM EDTA / Tris (pH 7.4), 150 mM NaCl, 5 mM KCl and 2 mM MgCl2) to achieve aprotein concentration of 150 µg / mL, in a 200 µL sample volumeProbe Substances alone, or in combination with Test Substances, were then added to thesamples and the sample incubated for 15 minutes (Probe Substance 1) or 180 minutes (ProbeSubstance 2) at 4oC. The structure of Probe Substances 1 and 2 are shown in Table 3 below:Table 3: Probe Substance No. StructureProbe Substance 1Probe Substance 2Next, the samples were added to AcroPrepTM GF / B filter plates, which have previously beenwetted with filter buffer (50 mM Tris / HCl (pH 7.4), and 0.001% N-dodecyl-^-maltoside), for 60minutes at room temperature. Excess filter buffer was then removed via centrifugation for 1minute at 1000 rpm. Samples were then filtered via centrifugation for 1 minute at 1000 rpm,and subsequently washed twice with filter buffer. Filters were dried for 45 minutes at a temperature of 50oC, and 150 µL elution buffer was added to each filter plate, filtered via centrifugation for 1 minute at 1000 rpm, and collected in a Waters 186002643 plate. The detection and quantification of the eluted Probe Substance in 20 µL sample was thenperformed using ultra high-performance liquid chromatography (UHPLC; C18 column;Poroshell 120 E-C18, on a 1290 Infinity Binary LC system, Agilent) coupled to triplequadrupole mass spectrometer (Triple Quad 5500 mass spectrometer with an ESI Turbo Vion source, SCIEX). In particular, chromatographic separation was optimised to define thegradient parameters necessary to elute Probe Substances 1 and 2 with optimal peak shapeand resolution. In addition, a multiple reaction monitoring (MRM) method was optimised usingelectrospray ionization in positive mode with the maximum selectivity and sensitivity found. The limit of detection (LoD) and limit of qualification (LoQ) values were 0.15 nM and 0.6 nMrespectively for Probe Substance 1 and 1.5 nM and 3 nM respectively for Probe Substance 2. Non-specific binding was defined and accounted for in subsequent experiments via addition of 10 µM of either Substance A, used for Probe Substance 1, or Substance B, used for ProbeSubstance 2, the structures of which are shown in Table 4 below:Table 4: Substance ID StructureSubstance ASubstance BPrior to screening a series of Test Substances using the filtration binding assay protocol described above, binding of Probe Substances 1 and 2 to NLRX1-expressing membranes was confirmed and similarly compared to binding of said Probe Substances to membranes derivedfrom cells which have not been transfected with NLRX1. For this experiment, Probe Substance1 was added to samples at a concentration of 1 nM and Probe Substance 2 was added tosamples at a concentration of 5 nM. The results are shown in Figures 6 and 7. In particular,the results confirm that Probe Substances 1 and 2 specifically bind to NLRX1-expressing membranes, but that said Probe Substances fail to bind to membranes derived from cellswhich have not been transfected with NLRX1. Subsequently, the same filtration binding assayprotocol was used to determine the Kdvalues associated with binding of Probe Substances 1 and 2 to NLRX1-expressing membranes, which were 7.1 nM and 1.1 nM respectively. Next, competition binding assays were performed using the above-described filtration binding assay protocol, to determine binding of Test Substances to NLRX1-expressing membranes. For the purposes of these experiments, Probe Substance 1 was added to samples at a concentration of 10 nM and Probe Substance 2 was added to samples at a concentration of 2 nM. Test Substances were added to samples at concentrations ranging between 10 µM and1 nM. Specific binding of Test Substances to NLRX1-expressing membranes was assessed via calculation of Kivalues. A summary of the Test Substances screened using the filtrationbinding assay protocol of the invention, and the Ki values derived from their screening (andthe Probe Substance said Test Substance was used to elute), are summarised in Table 5 below: Table 5: Test Substance No. Test Substance Structure Ki (nM)95.0 (Probe Test Substance 6 Substance 1) 13.0 (Probe Test Substance 7 Substance 2) 69.0 (Probe Test Substance 8 Substance 1) 2.8 (Probe Test Substance 9 Substance 1) 8.7 (Probe Test Substance 10 Substance 2) 23.0 (Probe Test Substance 11 Substance 1) 19.0 (Probe Test Substance 12 Substance 1) 5.4 (Probe Test Substance 13 Substance 2)These results show that the above-described filtration binding assay protocol is a suitablemethod for the identification of substances which bind to NLRX1, and in particular is capable of identifying substances which bind to NLRX1 with high affinity. NLRX1 Binding Example 3: Screening new substances for NLRX1 binding using a nano- BRET assay New substances may be screened for binding to NLRX1 using a nano-BRET assay, the protocol for which has been developed and optimised by the present inventors.Specifically, a vector comprising full length human NLRX1 (Uniprot ID Q86UT6) fused to aNanoLuc® tag (Promega) at the C-terminus in a pFC32 NanoLuc® Protein Fusion Flexi®Vector (Promega) was produced by DNA synthesis and molecular cloning. Next, HEK293Tcells (ECAAC; 2 x 105cells / mL) were transfected with the NLRX1-NanoLuc® vector (1 µg / mL) in the presence of 9 µg / mL carrier DNA (Promega), 10 µL FuGENE HD transfection reagent (Promega), and 1.5 mL OptiMEM (Invitrogen). Control samples were prepared similarly butwith replacement of the NLRX1- NanoLuc® vector with an equivalent volume of OptiMEM.Cell samples were incubated for 20 minutes at room temperature prior to mixing with lipid mixtures and subsequent incubation for 24 hours at 37oC, 5% CO2, in a humidified incubator. Following incubation, cells were harvested via trypsinization and seeded at about 20,000 cells / well into a 96-well plate (Corning).Test Substances were then added using the Multidrop Pico 8 dispenser device (ThermoFisherScientific), at a top concentration of 10 µM, and as a ten-point, 1:3, serial dilution in duplicate wells. A tracer molecule was then added at a final concentration of 1 µM to all wells of the 96- well plate. Samples were then incubated for 2 hours at 37oC, 5% CO2, in a humidified incubator. The tracer molecule was produced via click chemistry to conjugate the NanoBRETTM590- Azide-C3 (Promega) to the alkyne moiety of the below compound: Following incubation, 50 µL of a development solution of Nano-Glo® substrate (Promega)diluted 1 in 166 and supplemented with a 1 in 500 dilution of extracellular inhibitor in OptiMEM,was added to each well of the 96-well plate. The plate contents were then mixed by shaking and incubation for 10 minutes at room temperature. Assay signals (luciferase signal) were obtained using a CLARIOstar reader (top optic: Em:470 / 480; Em F: 615-18). The BRET ratio (acceptor 618 nm emission / donor 470 nm emission)for each concentration was obtained, multiplied by 1000 and then plotted. The results for thisanalysis for two Test Substances, 2 and 6, are shown in Figures 8 and 9. In particular, in thepresence of an increasing concentration of Test Substance 14, the BRET ratio decreased approximately two-fold, indicative of specific NLRX1 binding, whilst no such decrease wasseen in the presence of Test Substance 2. The structure of Test Substances 2 and 6 areillustrated in Table 6 below:Table 6: Test Substance No. Structure pIC50*Test Substance 2 < 5Test Substance 14 6.9**mean of 4 replicate experimentsThese results show that the above-described nano-BRET assay protocol is a suitable methodfor the identification of substances which bind to NLRX1, and in particular is capable ofidentifying substances which bind to NLRX1 with high affinity. In particular, Test Substance14 is demonstrated to bind NLRX1 with high affinity, whilst Test Substance 2 demonstratesno significant, specific, binding to NLRX1. NLRX1 Binding Example 4: Screening new substances for NLRX1 binding using a filtration binding assay New substances may be screened for binding to NLRX1 using a filtration binding assay, the protocol for which has been developed and optimised by the present inventors.Firstly, a radiolabelled Test Substance was produced via synthesis of tritium, [3H], labelledTest Substance 15, the structure of which is illustrated below: ,which radiolabelled Test Substance has a radioactive concentration of 1 mCi / mL and a specificactivity of 28 Ci / mmol.In order to evaluate the specificity of binding of radiolabelled Test Substance 15 to NLRX1,binding of said Test Substance to brain slices from wild-type and NLRX1-knockout mice wasevaluated by ex vivo autoradiography.Specifically, brains from an adult wild-type or NLRX1-knockout mice were dissected and freshfrozen at between -25 and -30 oC, using 2-methyl-butane to regulate the freezing process,prior to storage at -80 oC before use. For use, brains were sectioned coronally, from anteriorto posterior (to include the cortical region as well as both dorsal and ventral hippocampus), ona cryostat to provide brain slices of about 20 µm thickness, which slices are then placed onto 1 % gelatin-coated slides using the ‘freeze thaw’ method. Excess water was removed from thesections by incubating with CaSO4 for 1 hour at 4 oC before storing those sections at -80 oCuntil use. In use, the coronal brain sections were incubated with 3.3 nM radiolabelled Test Substance 15 for 120 minutes at 4oC, in the presence of an intracellular buffer comprising 50 mM Tris,10 mM NaCl, 0.5 mM MgCl2, 140 mM KCl, and having pH 7.0.The specific binding component was determined by incubating adjacent coronal brain sectionswith the radiolabelled Test Substance 15 (as above) in the presence of a saturatingconcentration (10 µM) of unlabelled Test Substance 15, which yields a measure of non-specificbinding. Triplicate 5 µL aliquots of each stock were counted on a beta counter to confirm theconcentration of each radioligand dilution. Following incubation, the coronal brain sectionswere washed twice (each time for 1 minute) in ice cold buffer (comprising 50 mM Tris and 1.4mM MgCl2, having pH 7.4 at 4 °C) before being briefly submerged in water to remove excesssalts. The coronal brain sections were then dried immediately in a continuous cool air streamovernight, prior to apposition.Total binding of 3.3 nM radiolabelled Test Substance 15 to wild-type brain slices was 22 ^ 4fmol / mg protein, whereas binding to NLRX1-knockout brain slices was below the limit ofquantification consistent with specific binding of the radioligand to NLRX1 (see Figure 19).Non-specific binding of Test Substance 15 to both wild-type and NLRX1-knockout brain slices,determined in the presence of 10 µM unlabelled Test Substance 15, was also below the limitof quantification (see Figure 19).To determine a Kd for the binding of Test Substance 15 to NLRX1, a saturation filtration bindingassay was performed using brain homogenates prepared from Sprague-Dawley rats.Specifically, fresh frozen brains from Sprague-Dawley rats (n = 15), were weighed andhomogenised in 5 x (w / v) sucrose buffer comprising 0.32 M sucrose, 5 mM Tris, and 1 mMMgCl2, and having pH 7.4, at 4°C. The homogenate was centrifuged at 32000 g at 4 oC for20 minutes. The resultant pellet was washed in the same buffer and centrifuged again at32000 g at 4 oC for 20 minutes. The pellet was then washed a further three times to obtain aP2 membrane homogenate. This final pellet was resuspended in wash buffer, i.e.50 mMTris, of pH 7.4 at 4°C. The protein concentration was determined by BCA assay (Pierce BCAkit) and the homogenate stored at 80 ⁰C. Next, rat brain homogenates were thawed on iceand made up to an assay volume of 0.25 mL per well, with 55 µg protein per well, usingintracellular buffer (comprising 50 mM Tris, 10 mM NaCl, 0.5 mM MgCl2, and 140 mM KCl,and having pH 7.0) at 4°C. Homogenate suspensions were then incubated at 4 oC for 120minutes with 0.1 to 150 nM radiolabelled Test Substance 15. As above, the specific bindingcomponent was determined by incubating the membrane suspension with radioligand in thepresence of a saturating concentration, 10 µM, of unlabelled Test Substance 15. Assayswere terminated by filtration through Whatman GF / B filters which were pre-soaked in 0.001% dodecyl maltopyranoside, before washing said filters four times with ice cold wash buffer comprising 50 mM Tris of pH 7.4 at 4°C. Known volumes of stock radioligand were counted to produce a standard curve.Using this method, the Kd for the binding of Test Substance 15 to NLRX1 was determined tobe 7.3 nM, which value was the mean of triplicate experiments (see Figure 20). Next, competition binding assays were performed using the above-described filtration binding assay protocol, to determine binding of Test Substances to NLRX1-expressing coronal brainsections. For the purposes of these experiments, radiolabelled Test Substance 15 was addedto coronal brain sections at a concentration of 10 nM. Test Substances were added to samplesat concentrations ranging between 10 µM and 0.01 nM. Specific binding of Test Substances to NLRX1-expressing membranes was assessed via calculation of Kivalues. A summary of the Test Substances screened using the filtration binding assay protocol of the invention, andthe Ki values derived from their screening are summarised in Table 7 below:Table 7: Test Substance No. Test Substance Structure Ki (nM)Test Substance 4 7.3Test Substance 5 5.3Test Substance 16 8.1Test Substance 17 8.1Test Substance 18 8.5Test Substance 19 7.6These results show that the above-described filtration binding assay protocol is a suitablemethod for the identification of substances which bind to NLRX1, and in particular is capable of identifying substances which bind to NLRX1 with high affinity. Inhibition of the mPTP Examples In view of the novel methods and assays which have been developed by the present inventors for the identification of substances which are capable of binding to NLRX1, the present inventors have further investigated whether said substances are capable of inhibiting the activity of the mPTP. Inhibition of the mPTP Example 1: Investigating the mPTP inhibitory activity of substances that bind to NLRX1 using an mPTP activity assay in isolated rat liver mitochondria As discussed above, pharmacological inhibition of the mPTP can be measured in ‘Ca2+retention’ assays performed in isolated mitochondria. Here, activity of the mPTP was measured in mitochondria freshly isolated from female Sprague Dawley (250 to 300 gram) rat livers. Firstly, cervical dislocation was performed onthe rat prior to perfusion of the liver in-situ with about 40 mL cold Dulbecco’s PhosphateBuffered Saline (DPBS). The liver was then dissected and transfered into 30 mL isolationbuffer (250 mM sucrose, 10 mM KCl, 1 mM EGTA, 1 mM EDTA, 25 mM HEPES, adjusted topH 7.5 with 1 M NaOH). Each lobe of the liver was then removed from the buffer, mincedusing tweezers and a scalpel into ~5 mm pieces then transferred into a 50 mL Pottertondounce homogenization tube on ice containing 30 mL ice-cold centrifugation buffer (300 mMtrehalose, 25 mM HEPES, 1 mM EGTA, 1 mM EDTA, 10 mM KCl, adjusted to pH 7.5 with 1M NaOH and supplemented with 0.1% bovine serum albumin (BSA) and complete proteaseinhibitor cocktail (one tablet of inhibitor per 50 mL buffer).Homogenisation was carried out using a teflon pestle at 1800 rpm. The slurry wascentrifuged at 800 g for 10 minutes at 4 oC, then the supernatant centrifuged at 10,000 g for10 minutes. The pellet was washed once with FLIPR assay buffer (75 mM mannitol, 25 mMsucrose, 5 mM potassium phosphate (monobasic), 20 mM Tris base, 100 mM KCl, 0.1 %BSA adjusted to pH 7.4 with 5 M HCl) centrifuged again, then resuspended in FLIPR assaybuffer to a concentration of 8.8 mg / mL protein.Test Substances (stored in 10 mM stock in DMSO) were serially diluted in DMSO in half logsteps to generate 10 test concentrations (final concentrations in assay 30 µM to 1 nM). An intermediate dilution of 5 µl DMSO samples into 247 µl FLIPR assay buffer was carried out prior to transfer of 5 µl into duplicate wells of a 384 well polypropylene assay plate. Control wells were 0.5 % (v / v) DMSO and 5 µM cyclosporin A.A stock mitochondria / Fluo5N assay solution was prepared in 5.6 mL FLIPR assay buffer (atroom temperature) supplemented with succinate disodium salt (10 mM), rotenone (1 µM),Fluo5N pentapotassium salt (2 µM) and 1 mL mitochondria suspension, prior to beingtransferred (15 µL) into the assay plate containing Test Substances and incubated for 10minutes at room temperature. Assay plates were then transferred to a FLIPR® Tetra PlateReader (Molecular Devices). Dye fluorescence was then measured every 3 seconds for atotal of 10 minutes. After 12 seconds, a 2.5 µL bolus of CaCl2 (75 µM) was added from asource plate containing 675 µM CaCl2 in FLIPR assay buffer. IC50 values for tested compounds were calculated using the fluorescence value collected at the 10 minutes timepoint with % inhibition calculated using the DMSO control and cyclosporin A values as 100 and 0 % respectively.The results of testing Test Substances 1 to 6 in the above-described mPTP activity assay areshown in Table 8 below:Table 8: Test Substance No. pIC50 from mPTP rat liver assay*Test Substance 1 7.9Test Substance 2 < 4.52Test Substance 3 6.7Test Substance 4 6.9Test Substance 5 5.5Test Substance 6 7.5Test Substance 7 6.4Test Substance 8 7.3Test Substance 9 8.4Test Substance 10 6.5Test Substance 11 8.0Test Substance 12 7.7Test Substance 13 6.7Test Substance 14 7.7*mean of 3 or more replicate experiments These results show that all Test Substances which are capable of binding to NLRX1 are also potent inhibitors of the activity of the mPTP. Moreover, it should be noted that, in general, the rank order of Test Substances in NLRX1 binding affinity correlates well with the rank order of said Test Substances in mPTP inhibitory activity. Test Substances 2 and 5, which fail to demonstrate any specific NLRX1 binding activity, similarly fail to inhibit the activity of the mPTPwith any significant potency. In particular, without wishing to be bound by theory, the presentinventors consider that any weak mPTP inhibitory activity of Test Substances 2 and 5 isobserved merely due to inclusion of said Test Substances at very high concentrations. Thisfurther supports the conclusion that inhibition of mPTP activity is mediated via binding to andconsequential regulatory modulation of NLRX1.Chemical Examples Chemical Example 1a: N-(2-Cyclopropyl-3-(2,4-difluorophenyl)propyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide (racemate)Synthesis To a flask purged and maintained with nitrogen was added cyclopropylacetonitrile (0.24 mL,2.66 mmol) and THF (6.0 m). The reaction mixture was cooled to -78 °C and LDA (2M inTHF / heptane / ethylbenzene, 2.9 mL, 2.90 mmol) added dropwise. The reaction mixture wasstirred at -78 °C for 1 hr. 2,4-Difluoro benzyl bromide (0.31 mL, 2.42 mmol) was added, andthe reaction mixture stirred at -78 °C for 1 hr. Water (10 mL) was added and the mixtureextracted with EtOAc (2 x 40 mL). The combined organics were passed through a phaseseparator cartridge (Biotage) and the filtrate evaporated in vacuo. The crude product waspurified by flash chromatography (Biotage, 10g Sfar column) eluting with isohexane-EtOAc (0- 20%) to yield 2-cyclopropyl-3-(2,4-difluorophenyl)propanenitrile (116 mg, 23 %) as a colourless oil.1H-NMR (400 MHz, DMSO-D6) δ 7.49-7.41 (m, 1H), 7.27-7.21 (m, 1H), 7.12- 7.06 (m, 1H), 3.00 (d, J = 7.3 Hz, 2H), 2.72-2.67 (m, 1H), 1.11-1.03 (m, 1H), 0.59-0.51 (m, 2H), 0.39-0.23 (m, 2H). To a flask purged and maintained with nitrogen was added 2-cyclopropyl-3-(2,4-difluorophenyl)propanenitrile (116 mg, 0.561 mmol) in THF (4.0 mL). The reaction mixture wascooled to 0 °C and LiAlH4 (1.0M in THF, 1.10 mL, 1.10 mmol) added dropwise at 0 °C. The reaction mixture was stirred at RT for 2 hrs. The reaction mixture was cooled to 0 °C, quenched with aqueous Rochelle's salt solution (5 mL) and extracted with EtOAc (30 mL). The organic phase was washed with sat. brine solution (30 mL), passed through a phase separatorcartridge (Biotage) and the filtrate evaporated in vacuo. The crude product was purified bycatch release cartridge (Biotage SCX-2), washing with MeOH and eluted with 1M NH3-MeOH.Fractions containing desired product were combined and the solvent evaporated in vacuo toyield 2-cyclopropyl-3-(2,4-difluorophenyl)propan-1-amine (53 mg, 24% ) as a pale-yellow oil.LC-MS in pH9; RT 1.54 min, MZ 212.2 [M+H]+ To 5-Hydroxy-1-methyl-1H-1,2,4-triazole-3-carboxylic acid (19 mg, 0.133 mmol), 2-cyclopropyl-3-(2,4-difluorophenyl)propan-1-amine (52 mg, 0.133 mmol) and DIPEA (0.069mL, 0.398 mmol) in DMF (2.5 mL) was added HATU (64 mg, 0.159 mmol), and the reactionmixture was stirred at RT for 2 hrs. The solvent was evaporated in vacuo and the crude productdirectly purified by prep-LCMS (2.4min_pH2 Formic acid, 30-72% MeCN followed by organicwash). Fractions containing desired product were combined and the solvent evaporated invacuo. The product was lyophilised from 1:1 MeCN-H2O to yield N-(2-cyclopropyl-3-(2,4-difluorophenyl)propyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide (11 mg, 25 %) as a white solid.1H-NMR (400 MHz, DMSO-D6) δ 12.18 (s, 1H), 8.50 (t, J = 6.0 Hz, 1H), 7.32 (q, J = 7.9 Hz, 1H), 7.08 (td, J = 10.0, 2.7 Hz, 1H), 6.95-6.92 (m, 1H), 3.30 (s, 3H), 3.23 (d, J = 6.0 Hz, 1H), 3.18-3.12 (m, 1H), 2.70-2.63 (m, 1H), 2.56 (dd, J = 13.7, 7.8 Hz, 1H), 1.09 (dt, J = 23.5, 7.0 Hz, 1H), 0.52-0.43 (m, 1H), 0.32-0.26 (m, 1H), 0.21-0.14 (m, 1H), -0.00 (td, J = 9.4, 4.7 Hz, 1H), -0.37 (td, J = 9.4, 4.9 Hz, 1H); QC in pH2 = 100%, RT 4.47 min, MZ 335.1 [M-H]-; QC in pH9 = 100%, RT 3.83 min, MZ 335.1 [M-H]- Chemical Examples 1b (mPTP Inhibitor 1) and 1c: (R)-N-(2-Cyclopropyl-3-(2,4- difluorophenyl)propyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide and (S)-N-(2-cyclopropyl-3-(2,4-difluorophenyl)propyl)-1-methyl-5-oxo-4,5-dihydro-1H- 1,2,4-triazole-3-carboxamide 50 mg of racemic compound (prepared according to Example 1a) was submitted for chiralseparation (Daicel ChiralPak AD, 250mm x 4.6mm, 5um; 50 / 50 Ethanol / Methanol + 0.1% TFA(overall) v / v) to give N-[(2R)-2-cyclopropyl-3-(2,4-difluorophenyl)propyl]-1-methyl-5-oxo-4H-1,2,4-triazole-3-carboxamide (22 mg, 0.0645 mmol) as a white solid and N-[(2S)-2-cyclopropyl-3-(2,4-difluorophenyl)propyl]-1-methyl-5-oxo-4H-1,2,4-triazole-3-carboxamide (22 mg, 0.0645 mmol) as a white solid.Stereochemistry was inferred and confirmed by X-ray crystallography. (R)-N-(2-Cyclopropyl-3-(2,4-difluorophenyl)propyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide:1H-NMR (400 MHz, DMSO-D6) δ 12.18 (s, 1H), 8.50 (t, J = 6.2 Hz, 1H), 7.32 (q, J = 8.1 Hz, 1H), 7.08 (td, J = 10.0, 2.6 Hz, 1H), 6.97-6.91 (m, 1H), 3.30 (s, 3H), 3.24 (t, J = 6.4 Hz, 1H), 3.18-3.12 (m, 1H), 2.67 (q, J = 6.6 Hz, 1H), 2.56 (dd, J = 13.5, 7.6 Hz, 1H), 1.14-1.05 (m, 1H), 0.47 (tt, J = 12.9, 4.7 Hz, 1H), 0.32-0.26 (m, 1H), 0.21-0.14 (m, 1H), -0.00 (td, J = 9.4, 5.0 Hz, 1H), -0.37 (td, J = 9.4, 4.9 Hz, 1H); (R)-N-(2-Cyclopropyl-3-(2,4-difluorophenyl)propyl)-1- methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide: QC in pH2 = 100%, RT 4.48 min, MZ 335.1 [M-H]-; QC in pH9 = 100%, RT 3.74 min, MZ 335.0 [M-H]- (S)-N-(2-cyclopropyl-3- (2,4-difluorophenyl)propyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxamide:1H-NMR (400 MHz, DMSO-D6) δ 12.22 (s, 1H), 8.55 (t, J = 6.2 Hz, 1H), 7.36 (q, J = 8.1 Hz, 1H),7.12 (td, J = 9.8, 2.7 Hz, 1H), 7.02-6.96 (m, 1H), 3.35 (s, 3H), 3.29 (t, J = 6.4 Hz, 1H), 3.23- 3.16 (m, 1H), 2.74-2.67 (m, 1H), 2.60 (dd, J = 13.7, 7.8 Hz, 1H), 1.18-1.09 (m, 1H), 0.52 (tt, J= 13.0, 4.9 Hz, 1H), 0.37-0.30 (m, 1H), 0.25-0.19 (m, 1H), 0.05 (td, J = 9.4, 4.9 Hz, 1H), -0.32(td, J = 9.4, 4.9 Hz, 1H); (S)-N-(2-cyclopropyl-3-(2,4-difluorophenyl)propyl)-1-methyl-5-oxo- 4,5-dihydro-1H-1,2,4-triazole-3-carboxamide: QC in pH2 = 100%, RT 4.48 min, MZ 335.1 [M- H]-; QC in pH9 = 100%, RT 3.74 min, MZ 335.0 [M-H]-Results: mPTP pIC50 values for compounds 1a to 1c in the mPTP assays described in GeneralMethods are provided below. The results indicate that the tested compounds displays potentinhibition of mPTP. Example No mPTP Rat livermPTP Rat brain pIC50* pIC50 1a 6.58 NT1b 6.76 7.911c 5.66 6.60*The examples were tested by different contract research organisation. Potencies as determined by the two organisations are believed to be comparable because tested standards had no notable differences between the two organisations. Biological Examples In addition to the novel methods and assays described above, the present inventors have also investigated the anti-inflammatory and therapeutic effect of inhibitors of the mPTP, whichinhibition is understood to be mediated via binding to NLRX1, in a range of models.Biological Example 1: Investigating the effect of mPTP Inhibitor 1 in a ΔNLS TDP43mouse model of amyotrophic lateral sclerosis (ALS)In the ΔNLS TDP43 mouse model, human TDP43 protein is expressed, via a transgene, withmutations introduced into the nuclear localisation sequence (NLS), such that the humanTDP43 protein is not imported in the nucleus but mis-localised to the cell cytoplasm and otherorganelles e.g. mitochondria. Mis-localisation of TDP43 in this mouse model is thought to resemble that observed in tissue samples / cells from amyotrophic lateral sclerosis (ALS)patients (Walker et al. 2015).Specifically, the human ΔNLS TDP43 transgene is under the control of the neurofilament (NF)gene promoter and is regulated by a doxycycline transactivation element.In the present study, ΔNLS TDP43 mice were generated by breeding NEFH-tTA (Jax stock 025397) with tetO-hTDP-43ΔNLS bigenic mice (Jax stock 014650). Animals were maintained in 12 / 12 light / dark cycles at a room temperature between 20-26°C and at a relative humidity around 50%. Food and water were provided ad libitum. Pregnant mice and females with offspring at pre-weaning age were provided with chow containing doxycycline (200 mg / kg) to repress the hTDP43 transgene in the pups during development. Pups were weaned at approximately 4 weeks of age, genotyped and kept on doxycycline (200 mg / kg)-containing chow until 7 weeks of age. Mice on study were placed on regular chow. Mice were group housed in OPTI-MICE ventilated cages (Animal Care Systems, CO). Animals were housed in same-genotype groups of control or transgenic mice. Mice in the same cage received the same treatment. Oral treatment with vehicle (n=15) or mPTP Inhibitor 1 (5 mg / ml solution in 2% DMSO, 5%Cremaphor in sterile water) at the indicated doses (50 mg / kg or 150 mg / kg, n=14) was initiatedin parallel with doxycycline withdrawal. After 14 or 28 days of twice-daily dosing, plasma,cerebrospinal fluid (CSF) and brain tissue samples were collected for analysis.Specifically, mice were anaesthetised via isoflurane administration, placed in a stereotaxicframe and CSF isolated via cisterna magna puncture. Isolated CSF was centrifuged at 5000rpm for 1 min and snap frozen on dry ice prior to storage at -80oC. Next, blood was collectedin EDTA-coated tubes via cardiac puncture. Plasma was isolated from whole blood by centrifugation of the blood sample at 4oC for 15 min at 3000 x g, followed by removal of the plasma supernatant, which was subsequently aliquoted and frozen at -80oC. Finally, brain tissue (i.e. brain cortices) was collected and separated into hemispheres for dissection. Individual cortices were divided into left and right portions, and snap frozen or preserved in RNAlater. The structure of mPTP Inhibitor 1 is as follows: Firstly, to investigate the effect of mPTP Inhibitor 1 on neurodegeneration, neurofilament-light(NFL) protein levels were quantified in plasma and CSF after 14 days of twice-daily dosing. Inparticular, NFL protein levels were determined via Quanterix assay, using the NF-Light V2Advantage Kit and the Quanterix SIMOA® assay (Quanterix Cat # 104073). The results areillustrated in Figure 10 (error bars are SEM; statistical significance determined by one-wayANOVA with Tukey’s correction for multiple testing; * =0.05, ** = 0.01, *** = 0.005, ****=0.001). The results of Figure 10 illustrate that a significant increase in NFL expression was observedin both the plasma and CSF of ΔNLS TDP43 mice relative to wild-type mice. However,treatment of ΔNLS TDP43 mice with mPTP Inhibitor 1 at either 50 mg / kg or 150 mg / kg (for 14 days) resulted in a significant reduction in NFL expression in both the plasma (64% for 50 mg / kg, 53% for 150 mg / kg) and the CSF (20% for 50 mg / kg, 62% for 150 mg / kg).Furthermore, to investigate the anti-inflammatory effect of mPTP Inhibitor 1 in the ΔNLSTDP43 mouse model of amyotrophic lateral sclerosis (ALS), the level of expression of the astrocyte activation marker, GFAP, in the plasma, and the level of expression of the pro-inflammatory cytokine IL-1β, in the brain cortices, were quantified. In particular, GFAP levelswere determined via Quanterix assay, using the GFAP SR-X kit. Separately, IL-1β levels weredetermined via lysis of individual mice brain cortices in assay kit lysis buffer (MSD, V-Plex PlusMouse IL-1β) and subsequent assaying according to the manufacturers’ instructions.The results of the GFAP expression assay are illustrated in Figure 11 (error bars are SEM; statistical significance determined by one-way ANOVA with Tukey’s correction for multiple testing; * =0.05, ** = 0.01, *** = 0.005, ****=0.001). The results of Figure 11 illustrate that a significant increase in GFAP expression was observed in the plasma of ΔNLS TDP43 mice relative to wild-type mice. However, treatment of ΔNLS TDP43 mice with mPTP Inhibitor 1 ateither 50 mg / kg or 150 mg / kg (for 14 days) resulted in a significant reduction in GFAPexpression in the plasma (79% for 50 mg / kg, 88% for 150 mg / kg). This result is indicative of treatment with mPTP Inhibitor 1 resulting in dampened neuroinflammation in ΔNLS TDP43mice. In a repeat experiment, ΔNLS TDP43 mice were alternatively treated with mPTPInhibitor 1 at either 10 mg / kg or 50 mg / kg (for 14 days). The results of this repeat GFAP expression assay are illustrated in Figure 12 (error bars are SEM; statistical significance determined by one-way ANOVA with Tukey’s correction for multiple testing; * =0.05, ** = 0.01,*** = 0.005, ****=0.001). The results of Figure 12 similarly illustrate that treatment of ΔNLSTDP43 mice with mPTP Inhibitor 1 at either 10 mg / kg or 50 mg / kg (for 14 days, n=12) resulted in a significant reduction in GFAP expression in the plasma. That is, even at a lower dose of 10 mg / kg, treatment of ΔNLS TDP43 mice with mPTP Inhibitor 1, leads to a significantreduction in neuroinflammation, as represented by a reduction in GFAP expression.The results of the IL-1β expression assay are illustrated in Figure 13 (error bars are SEM; statistical significance determined by one-way ANOVA with Tukey’s correction for multipletesting; * =0.05, ** = 0.01). The results of Figure 13 illustrate that a significant increase in IL-1β expression is observed in the brain cortices of ΔNLS TDP43 mice relative to wild-type mice.This observation is consistent with induction of neuroinflammatory pathways. However,treatment of ΔNLS TDP43 mice with mPTP Inhibitor 1 at 50 mg / kg (for 14 days) resulted in a significant reduction in IL-1β expression, which is representative of dampened neuroinflammation. In addition, the effect of mPTP Inhibitor 1 on inflammation in the brain cortices of ΔNLS TDP43 mice was investigated by quantifying the expression levels of an array of mRNA transcripts inthe brain tissue. Specifically, transcriptional expression levels were assessed via RNAseq. Inparticular, RNA was isolated from samples of the brain cortices and preserved in RNAlaterusing QIAzol lysis reagent. Next, samples were lysed, by mechanical disruption, using aTissueLyser (Qiagen) with 5 mm stainless steel beads in 750 µl QIAzol lysis buffer. IsolatedRNA was purified using RNeasy96 Universal Tissue Kit (Qiagen) and stored at -80oC prior touse. Directional mRNA libraries were prepared by PolyA enrichment, and samples weresequenced using Illumina PE150 Sequencing with 8 G of raw data per sample (Novogene).Differential Expressed Gene (DEG) analysis was performed by Fios Genomics. In total, 7694 mRNA transcripts (p.adj. < 0.05) were altered in ΔNLS TDP43 mice relative to wild-type mice. Treatment of ΔNLS TDP43 mice with mPTP Inhibitor 1 resulted in a significant change in the expression of 143 mRNA transcripts, 74 of which were also differentially expressed between ΔNLS TDP43 and wild-type mice. As illustrated in Figure 14, the effect of treatment with mPTP Inhibitor 1 was to normalise expression of 73 of the aforementioned 74 mRNA transcripts back in the direction towards that observed in wild-type mice. That is,treatment of ΔNLS TDP43 mice with mPTP Inhibitor 1 results in normalisation of a subset ofthe transcriptome to the wild-type, i.e. disease-free phenotype. Upon further analysis, it was identified that a number of mRNA transcripts within the 74 ofwhich were differentially expressed between both ΔNLS TDP43 mice and wild-type mice, andΔNLS TDP43 mice treated with vehicle and ΔNLS TDP43 mice treated with mPTP Inhibitor 1, are associated with inflammation, and in particular are regulated by production of the pro-inflammatory cytokines, interferons. In particular, 12 specific genes / mRNA transcripts wereselected for further validation via qPCR, in an independent experiment. Specifically, mPTPInhibitor 1 was orally administered, at a dose of either 10 mg / kg or 50 mg / kg, to ΔNLS TDP43mice 28 days, and the expression of said 12 specific genes in the brain cortical cell lysateswas quantified and assessed via qPCR. qPCR analysis was performed by reverse transcribing total RNA (1 µg of RNA in 20µL volume) into cDNA using the SuperScriptTM IV VILOTMMaster Mix with ezDNaseTM enzyme kit. Next, a 1 in 10 dilution of cDNA was used as inputfor qPCR assays for the genes of interest, namely Bst2, Stat1, Tspo, Lgals3bp, Ifi27, ISG15, Ifit3, Oasl1, Ifitm3, Ccl4, GFAP, CXCL10 together with the housekeeping gene Gapdh. The output from each qPCR was quantified using the delta delta Ct method and normalised to theequivalent value from the GADPH qPCR assay.The results of this analysis, and corresponding results for said 12 genes in the RNAseq analysis, are shown in Figure 15 and Figure 16. Regarding Figure 16, representative data isshown for two of the 12 specific genes of interest, ISG15 and GFAP (error bars are SEM;statistical significance determined by one-way ANOVA with Tukey’s correction for multipletesting; * =0.05, ** = 0.01, *** = 0.005, ****=0.001). The results of Figures 15 and 16 illustratethat each of the 12 specific genes / mRNA transcripts were significantly upregulated (i.e.expression thereof was increased) in ΔNLS TDP43 mice relative to wild-type mice. However,treatment of ΔNLS TDP43 mice with mPTP Inhibitor 1 significantly reduced the expression ofeach of the 12 specific genes / mRNA transcripts. Notably, the reduction in expression quantified was similar between the RNAseq and qPCR assays. In summary, these results suggest that in the ΔNLS TDP43 mouse model, which is thought to resemble the conditions in amyotrophic lateral sclerosis (ALS) patients, treatment with mPTPInhibitor 1 leads to a significant reduction in inflammation, as represented by a reduction inthe expression of pro-inflammatory genes and markers, and a significant reduction in neurodegeneration, as represented by a reduction in the expression of NFL, which is a marker of neurodegeneration. Biological Example 2: Investigating the effect of mPTP Inhibitor 1 in a pilocarpine induced rat seizure modelThe neuroprotective and anti-inflammatory effects mPTP Inhibitor 1 were evaluated in a ratseizure model. In particular, status epilepticus was induced in male Sprague-Dawley (SD) ratsvia administration of pilocarpine. Seizures were monitored for 90 min, before being terminatedvia administration of sodium pentobarbital. Animals were allowed to recover for 24 hours,before terminal tissues were collected for biomarker analysis.Specifically, male SD rats (n = 6-10 / group; approx. 7 weeks old at study start, Beijing VitalRiver Laboratory Animal Technology Co., Ltd) were intraperitoneally administered lithiumchloride (Sigma, US; 127 mg / kg in saline) one day prior to the study start, followed byintraperitoneal administration of scopolamine methylbromide (2 mg / kg in saline) 24 hours later to minimise peripheral muscarinic cholinergic effects. mPTP Inhibitor 1 was administered orally one hour prior to pilocarpine treatment. Then, seizures were induced in rats via intraperitoneal injection of 15 mg / kg pilocarpine hydrochloride (MedChem Express, dissolvedin saline). Seizure intensity was measured using the Racine scale, with seizures above Grade4 classified as status epilepticus (SE). After 90 min of SE, seizures were terminated viaintraperitoneal administration of sodium pentobarbital (32.5 mg / kg). Animals were allowed torecover for 24 hours, prior to biomarker analysis.Next, animals were euthanised via isoflurane overdose. CSF was recovered from the subduralregion and stored at -80oC. Blood was collected in EDTA coated tubes, spun at 4000 x g at4oC for 5 min to isolate plasma which was then aliquoted and stored at -80oC. The brains ifindividual animals were removed, sectioned into the left and right cortex, and further dividedinto the posterior and anterior regions. Each section was flash-frozen in liquid nitrogenimmediately after collection and stored at -80oC until required.Expression of cytokine transcripts was quantified via qPCR. In particular, RNA was extractedfrom approximately 50 mg brain tissue from the right posterior cortex. The brain tissue wasincubated in 1 mL QIAzol Lysis reagent and homogenised using a TissueLyser II (Qiagen).RNA was then isolated using chloroform and subsequently processed using a QIAgen RNeasyLipid Tissue Mini kit, according to the manufacturers’ instruction. Reverse transcription wasperformed on 2 µg total RNA using the Invitrogen High Capacity RNA-to-cDNA kit, accordingto the manufacturers’ instructions. Next, transcript levels were determined using the TaqmanFAST gene expression assay for the targets of interest. Expression levels were determined using the deltaCt method, with each transcript of interest (TNF, IL-6, IL1b, CCL2) beingnormalised to the housekeeping gene, GAPDH. Data for each transcript of interest wassubsequently normalised to the vehicle control, allowing relative changes to be accurately compared.The results are illustrated in Figure 17 (error bars are SEM; statistical significance determinedby one-way ANOVA with Dunnett’s correction for multiple correlation; * =0.05, ** = 0.01, *** = 0.005, ****=0.001). The results of Figure 17 illustrate that a significant increase in the expression of pro-inflammatory cytokine transcripts, namely TNFα, IL-6, IL-1β, and CCL2, was observed in rats treated with pilocarpine, and thus induced into a seizure, relative to rats treated with saline only, 24 hours post-treatment. However, oral treatment of pilocarpine- treated mice with mPTP Inhibitor 1, at a dose of either 50 mg / kg or 150 mg / kg, resulted in a significant decrease in the level of expression of each of these pro-inflammatory cytokinetranscripts. Notably, the 150 mg / kg dose of mPTP Inhibitor 1 elicited a more significantreduction in the expression of said pro-inflammatory cytokine transcripts than the 50 mg / kg dose. These results suggest that treatment with mPTP Inhibitor 1 has an anti-inflammatoryeffect in the pilocarpine induced rat seizure model.In addition, to investigate the effect of mPTP Inhibitor 1 on neurodegeneration, neurofilament- light (NFL) protein levels were quantified in plasma and CSF after 24 hours post-treatment. Specifically, NFL expression was quantified using the Uman Diagnostic NF-Light kit, usedaccording to the manufacturer’s instructions. As appropriate, samples were diluted in kitsample diluent to ensure measured values were within the linear range of the assay. NFL levels in each sample were quantified by converting measured absorbance to a standard curve, then subsequently normalised by reference to samples from saline treated rats (0% effect) and samples from pilocarpine treated rats (100% effect).The results are illustrated in Figure 18 (error bars are SEM; statistical significance determinedby one-way ANOVA with Dunnett’s correction for multiple correlation; * =0.05, ** = 0.01, *** =0.005, ****=0.001). The results of Figure 18 illustrate that a significant increase in NFLexpression was observed in both the plasma and CSF of rats treated with pilocarpine, and thus induced into a seizure, relative to rats treated with saline only, 24 hours post-treatment. However, treatment of pilocarpine-treated mice with mPTP Inhibitor 1, at a dose of 10 mg / kg,50 mg / kg, or 150 mg / kg, resulted in a significant reduction in expression of NFL in both theplasma and CSF. Notably, the reduction in NFL expression observed following treatment of pilocarpine-treated mice with mPTP Inhibitor 1 appeared to be dose-dependent. These resultssuggest that treatment with mPTP Inhibitor 1 has a neuroprotective effect in the pilocarpineinduced rat seizure model. In summary, these results suggest that in pilocarpine induced rat seizure model, treatmentwith mPTP Inhibitor 1 has a potent anti-inflammatory effect, as represented by a reduction in the expression of pro-inflammatory cytokine transcripts, and has a significant neuroprotective effect (i.e. protects against neurodegeneration), as represented by a reduction in the expression of NFL, which is a marker of neurodegeneration. Summary In summary, these results demonstrate that methods developed by the present inventors,which comprise (i) identifying a substance which is capable of binding to NLRX1, for examplevia one of the assays described above, and (ii) confirming that said substance is capable ofinhibiting the activity of the mPTP, for example via the mPTP activity assay described above, are entirely suitable for the identification of new substances which may have utility in thetreatment of diseases, disorders, or conditions associated with altered NLRX1 activity , and inparticular in the treatment of diseases, disorders, or conditions associated with activation ofthe mPTP. Moreover, these results demonstrate that mPTP inhibitors, and specifically mPTP Inhibitor 1,have a potent anti-inflammatory and neuroprotective effect in two distinct animal models. It istherefore similarly envisaged that new substances, which are inhibitors of the mPTP, identified by the methods developed by the present inventors, will have a similar effect. Therefore, mPTP inhibitors, including new substances identified by the methods described herein, areexpected to have utility in the treatment of diseases, disorders, or conditions associated withaltered NLRX1 activity and, in particular, in the treatment of diseases, disorders, or conditionsassociated with activation of the mPTP.Miscellaneous All references referred to in this application, including patent and patent applications, are incorporated herein by reference to the fullest extent possible. Throughout the specification and the claims which follow, unless the context requires otherwise, the word ‘comprise’, and variations such as ‘comprises’ and ‘comprising’, will be understood to imply the inclusion of a stated integer, step, group of integers or group of steps but not to the exclusion of any other integer, step, group of integers or group of steps. The application of which this description and claims form part may be used as a basis for priority in respect of any subsequent application. The claims of such subsequent application may be directed to any feature or combination of features described herein. They may take the form of product, composition, process, or use claims and may include, by way of example and without limitation, the following claims. The invention embraces all combinations of preferred and more preferred groups and suitable and more suitable groups and embodiments of groups recited above. 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Claims

CLAIMS:

1. A substance which is (i) capable of binding to NLRX1 and (ii) capable of inhibiting theactivity of the mPTP, for use in the prevention or treatment of a disease, disorder, orcondition associated with altered NLRX1 activity.

2. The substance for use according to claim 1, wherein the disease, disorder, orcondition is associated with activation of the mPTP.

3. The substance for use according to claim 2, wherein the disease, disorder, orcondition is a degenerative or neurodegenerative disease, disorder, or condition, for exampleselected from Parkinson’s disease, dementia with Lewy bodies, Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis, frontal temporal dementia, chemotherapy induced neuropathy, Huntington’s disease, epilepsy, Charcot-Marie-Tooth disease, multiplesystem atrophy, spinocerebellar ataxias, progressive supranuclear palsy, hereditary spasticparaplegia, Duchenne muscular dystrophy, congenital muscular dystrophy, inclusion body myositis, traumatic brain injury and Friedreich’s ataxia.

4. The substance for use according to claim 3, wherein the disease, disorder, orcondition is Parkinson’s disease.

5. The substance for use according to claim 3, wherein the disease, disorder, orcondition is amyotrophic lateral sclerosis.

6. A method for identifying a substance useful for the prevention or treatment of a disease, disorder, or condition associated with altered NLRX1 activity, which method comprises determining whether said substance (i) binds to NLRX1 and (ii) inhibits activity of the mPTP and, if it does, identifying said substance as a substance useful for the prevention or treatment of said disease, disorder, or condition associated with altered NLRX1 activity.

7. The method according to claim 6, wherein the disease, disorder, or condition isassociated with activation of the mPTP.

8. The method according to claim 7, wherein the disease, disorder, or condition is adegenerative or neurodegenerative disease, disorder, or condition, for example selected from Parkinson’s disease, dementia with Lewy bodies, Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis, frontal temporal dementia, chemotherapy inducedneuropathy, Huntington’s disease, epilepsy, Charcot-Marie-Tooth disease, multiple systematrophy, spinocerebellar ataxias, progressive supranuclear palsy, hereditary spasticparaplegia, Duchenne muscular dystrophy, congenital muscular dystrophy, inclusion body myositis, traumatic brain injury and Friedreich’s ataxia.

9. The method according to claim 8, wherein the disease, disorder, or condition isParkinson’s disease.

10. The method according to claim 8, wherein the disease, disorder, or condition isamyotrophic lateral sclerosis.

11. The method according to any one of claims 6 to 10, wherein the determination ofwhether said substance binds to NLRX1 is performed by means comprising a thermal shift assay of NLRX1 binding.

12. The method according to claim 11, wherein the determination of whether a substancebinds to NLRX1 is performed by means comprising a cellular thermal shift assay (CETSA).

13. The method according to any one of claims 6 to 10, wherein the determination ofwhether said substance binds to NLRX1 is performed by means comprising a filtrationbinding assay of NLRX1 binding.

14. The method according to any one of claims 6 to 10, wherein the determination ofwhether said substance binds to NLRX1 is performed by means comprising a proximityassay of NLRX1 binding.

15. The method according to claim 14, wherein the determination of whether a substancebinds to NLRX1 is performed by means comprising a bioluminescence resonance energy transfer (BRET) assay, and in particular is a nano-BRET assay, of NLRX1 binding.

16. The method according to any one of claims 6 to 15, wherein the determination ofwhether a substance inhibits the activity of the mPTP is performed by means comprising a mitochondrial calcium retention assay.

17. A substance which is (i) capable of binding to NLRX1 and (ii) capable of inhibiting theactivity of the mPTP identified by the method of any one of claims 6 to 16.

18. A substance according to claim 17, for use in the prevention or treatment of adisease, disorder, or condition associated with altered NLRX1 activity.

19. A substance according to claim 18, for use in the prevention or treatment of adisease, disorder, or condition associated with activation of the mPTP.

20. The substance for use according to claim 19, wherein the disease, disorder, orcondition is a degenerative or neurodegenerative disease, disorder, or condition, for example selected from Parkinson’s disease, dementia with Lewy bodies, Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis, frontal temporal dementia, chemotherapyinduced neuropathy, Huntington’s disease, epilepsy, Charcot-Marie-Tooth disease, multiplesystem atrophy, spinocerebellar ataxias, progressive supranuclear palsy, hereditary spasticparaplegia, Duchenne muscular dystrophy, congenital muscular dystrophy, inclusion body myositis, traumatic brain injury and Friedreich’s ataxia.

21. The substance for use according to claim 20, wherein the disease, disorder, orcondition is Parkinson’s disease.

22. The substance for use according to claim 20, wherein the disease, disorder, orcondition is amyotrophic lateral sclerosis.

23. An assay method for a substance that binds to NRLX1 which comprises meanscomprising a cellular thermal shift assay (CETSA) of NLRX1 binding, wherein the CETSAcomprises:(i) contacting a test substance with cells expressing NLRX1 to produce a test sample;(ii) exposing the test sample to a stepwise heat challenge; (iii) calculating the Tm value of the test sample; and (iv) comparing the Tm value of the test sample to the Tm value of a control sample; wherein binding to NLRX1 is indicated by an increased Tm value of the test sample relative to the Tm value of a control sample.

24. An assay method for a substance that binds to NRLX1 which comprises meanscomprising a filtration binding assay of NLRX1 binding, wherein the filtration binding assaycomprises:(i) contacting a probe substance, which binds to NLRX1, with membranes on which NLRX1 ispresent;(ii) filtering test substances through said membranes on which NLRX1 is present; and(iii) detecting, and optionally quantifying, the amount of test substance binding to membraneson which NLRX1 is present, or detecting, and optionally quantifying, the amount of probesubstance displaced from binding to membranes on which NLRX1 is present;wherein binding to NLRX1 is indicated by detection, and optional quantification, of testsubstance binding to membranes on which NLRX1 is present or detection, and optionalquantification, of probe substance displaced from binding to membranes on which NLRX1 ispresent.

25. An assay method for a substance that binds to NRLX1 which comprises meanscomprising a filtration binding assay of NLRX1 binding, wherein the filtration binding assay comprises: (i) contacting a test substance with NLRX1, to produce a test sample; (ii) filtering the test sample through a filter, on which NLRX1 is retained;(iii) detecting, and optionally quantifying, the amount of test substance which is retained onthe filter;wherein binding to NLRX1 is indicated by detection, and optional quantification, of testsubstance retained on the filter.

26. An assay method for a substance that binds to NRLX1 which comprises meanscomprising a bioluminescence resonance energy transfer (BRET) assay, and in particular anano-BRET assay, of NLRX1 binding, wherein the BRET or nano-BRET assay comprises:(i) contacting a test substance with cells expressing an NLRX1-luciferase construct to produce a test sample; (ii) contacting a tracer molecule, which comprises a substance known to bind to NLRX1 and a substance which is required for luciferase activity, with the test sample; and (iii) contacting luciferase substrate with the test sample; and (iv) quantifying the luciferase signal of the test sample; wherein binding to NLRX1 is indicated by a decrease in the luciferase signal relative to a control sample.

27. An assay method for a substance that binds to NRLX1 which comprises meanscomprising a bioluminescence resonance energy transfer (BRET) assay, and in particular anano-BRET assay, of NLRX1 binding, wherein the BRET or nano-BRET assay comprises:(i) contacting a test substance with cells expressing an NLRX1-luciferase construct to produce a test sample; (ii) contacting a tracer molecule, which comprises a substance known to bind to NLRX1 and a substance which is required for luciferase activity, with the test sample; and(iii) contacting luciferase substrate with the test sample; and (iv) quantifying the light emission signal of the NLRX1-luciferase test sample and the fluorescence of the tracer molecule; wherein binding to NLRX1 is indicated by a change in the BRET ratio relative to a control sample.

28. A substance of formula (I):wherein: R1a is H or methyl; R1b is H or F; A is group (Aa), (Ab), (Ac) or (Ad): wherein group (Aa) is:wherein: R2is H, C1-4alkyl, C1-4alkylene(aryl), C1-4alkylene(OH), C1-4alkylene(C3-6cycloalkyl), C1-4alkylene(4-7 membered heterocycloalkyl), C1-4alkoxy, OC1-4alkylene(aryl), C1-4alkyleneOC1-4alkyl, C1-4alkyleneOC3-6cycloalkyl, C1-4alkyleneO(4-7 membered heterocycloalkyl), C1-4alkyleneO(aryl), C3-6alkynyl or C1-4alkenylO(C3-6alkynyl); wherein said aryl, heterocycloalkyl and cycloalkyl are optionally substituted by 1, 2 or 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR2aR2b, SO2R2cand NHSO2R2c; R2ais selected from H and C1-4alkyl; R2bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R2cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; each R3is independently halo, methyl, ethyl or n-propyl; m is 0, 1, 2, 3 or 4; wherein group (Ab) is:wherein: R4 is H, C1-4alkyl or C1-4alkylene(aryl); wherein said aryl is optionally substituted by 1, 2 or 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1- 4alkoxy, C1-4haloalkyl, halo, CN, OH, NR4aR4b, SO2R4c and NHSO2R4c; R4a is selected from H and C1-4alkyl; R4b is selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R4c is selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R5 is H or C1-4alkyl; each R6 is independently C1-4alkyl or halo; n is 0, 1, 2 or 3; wherein group (Ac) is:wherein: R7is C1-4alkyl, C1-4alkylene(OH) or C1-4alkyleneOC1-4alkyl; o is 1 or 2; wherein group (Ad) is:wherein: X is a bond, O or CH2; each R8 is independently halo, C1-4alkyl, C1-4alkoxy, OC1-4haloalkyl, OC1-4alkylene(C3- 6cycloalkyl), OC1-4alkylene(4-7 membered heterocycloalkyl) or OH; wherein said heterocycloalkyl and cycloalkyl are optionally substituted by 1, 2 or 3 substituentsindependently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR8aR8b, SO2R8cand NHSO2R8c; R8ais selected from H and C1-4alkyl; R8bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R8cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; each R9is independently halo or C1-4alkyl; p is 0, 1 or 2; q is 0, 1, 2, 3 or 4; wherein B is group (Ba), (Bb) or (Bc): wherein group (Ba) is:wherein: Y is C(R11)(R12), N(R13), O or S; each R10 is independently halo or C1-4alkyl; r is 0, 1, 2 or 3; R11 is H or C1-4alkyl; R12 is H or C1-4alkyl; or R11 and R12 together with the carbon atom to which they are attached form a C3-6cycloalkyl; R13 is H, C1-4alkyl or C3-6cycloalkyl; wherein said cycloalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR13aR13b, SO2R13cand NHSO2R13c; R13ais selected from H and C1-4alkyl; R13b is selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R13cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; wherein group (Bb) is:wherein: each R14 is independently halo or C1-4alkyl; s is 0, 1, 2 or 3; wherein group (Bc) is:wherein: R15 is C1-4alkyl, C1-4alkoxy, C3-6cycloalkyl, C1-4haloalkyl, halo or CN; wherein said cycloalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR15aR15b, SO2R15c and NHSO2R15c; R15a is selected from H and C1-4alkyl; R15b is selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R15cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R16is H, halo or C1-4alkyl; and D, E and F are each independently C(R16); or one of D, E and F is N, and the two remaining D, E and F groups are independently C(R16); or a pharmaceutically acceptable salt and / or solvate thereof, for use in the prevention or treatment of a disease, disorder, or condition which is an Other NLRX1-Related Disease, Disorder or Condition.

29. A substance of formula (II):wherein: R1a is H or methyl;R1bis H or fluoro; A is group (Aa), (Ab), (Ac) or (Ad): wherein group (Aa) is:wherein: R2 is H, C1-4alkyl, C1-4alkylene(aryl), C1-4alkylene(OH), C1-4alkylene(C3-6cycloalkyl), C1- 4alkylene(4-7 membered heterocycloalkyl), C1-4alkoxy, OC1-4alkylene(aryl), C1-4alkyleneOC1-4alkyl, C1-4alkyleneOC3-6cycloalkyl, C1-4alkyleneO(4-7 membered heterocycloalkyl), C1-4alkyleneO(aryl), C3-6alkynyl and C1-4alkyleneO(C3-6alkynyl); wherein said aryl, heterocycloalkyl or cycloalkyl are optionally substituted by 1, 2 or 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR2aR2b, SO2R2c and NHSO2R2c; R2a is selected from H and C1-4alkyl; R2b is selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R2c is selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; each R3 is independently halo, methyl, ethyl or n-propyl; m is 0, 1, 2, 3 or 4; wherein group (Ab) is:wherein: R4is H, C1-4alkyl or C1-4alkylene(aryl); wherein said aryl is optionally substituted by 1, 2 or 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR4aR4b, SO2R4c and NHSO2R4c; R4ais selected from H and C1-4alkyl; R4bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl;R4cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R5is H or C1-4alkyl; each R6is independently C1-4alkyl or halo; n is 0, 1, 2 or 3; wherein group (Ac) is:wherein: R7 is C1-4alkyl, C1-4alkylene(OH) or C1-4alkyleneOC1-4alkyl; o is 1 or 2; wherein group (Ad) is:wherein: X is a bond, O or CH2; each R8is independently halo, C1-4alkyl, C1-4alkoxy OC1-4haloalkyl, OC1-4alkylene(C3-6cycloalkyl), OC1-4alkylene(4-7 membered heterocycloalkyl) or OH; wherein said heterocycloalkyl and cycloalkyl are optionally substituted by 1, 2 or 3 substituents independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR8aR8b, SO2R8cand NHSO2R8c; R8ais selected from H and C1-4alkyl; R8bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; R8cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-7 membered heterocycloalkyl; each R9 is independently halo or C1-4alkyl; p is 0, 1 or 2; q is 0, 1, 2, 3 or 4; wherein B is:wherein: R10 is H, halo or C1-4alkyl; D, E and F are each independently C(R10); or one of D, E and F is N and the two remaining D, E and F groups are independently C(R10); or a pharmaceutically acceptable salt and / or solvate thereof, for use in the prevention or treatment of a disease, disorder, or condition which is an Other NLRX1-Related Disease, Disorder or Condition.

30. A substance of formula (III):wherein: R1ais H or methyl; R1bis H or F; A is group (Aa), (Ab), (Ac), (Ad) or (Ae): wherein group (Aa) is:wherein: R2 is H, halo, C1-4alkyl, C1-4haloalkyl, C1-4alkylene(aryl), C1-4alkylene(OH), C1- 4alkylene(C3-6cycloalkyl), C1-4alkylene(4-10 membered heterocycloalkyl), 4-10 membered heterocycloalkyl, C1-4alkoxy, OC1-4alkylene(aryl), C1-4alkyleneOC1-4alkyl, C1-4alkyleneOC3-6cycloalkyl, C1-4alkyleneO(4-10 membered heterocycloalkyl), C1- 4alkyleneO(aryl), C3-6alkynyl, C1-4alkenylO(C3-6alkynyl), C1-4alkylene(CO2H); OC1- 4alkylene(CO2H), C1-4alkyleneOC1-4alkylene(CO2H), N(R2aa)C1-4alkylene(CO2H), C1- 4alkylene(NR2abR2ac), OC1-4alkylene(NR2abR2ac) or N(R2aa)C1-4alkylene(NR2abR2ac); wherein said aryl, heterocycloalkyl and cycloalkyl are optionally substituted by 1, 2 or3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR2aR2b, SO2R2cand NHSO2R2c; R2ais selected from H and C1-4alkyl; R2bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R2cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; each R2aais independently selected from H and C1-4alkyl; each R2abis independently selected from H and C1-4alkyl; each R2acis independently selected from H and C1-4alkyl; or R2aband R2actogether with the nitrogen atom to which they are attached form a 4-10 membered heterocycloalkyl; R2xis H, halo, C1-4alkyl, C1-4haloalkyl or C1-4alkoxy; each R3is independently halo, C1-4alkyl, C1-4haloalkyl or C1-4alkoxy; m is 0, 1,2 or 3; or; R2x is C1-4alkylene(4-10 membered heterocycloalkyl), 4-10 membered heterocycloalkyl, C1-4alkyleneO(4-10 membered heterocycloalkyl), C1- 4alkylene(CO2H), OC1-4alkylene(CO2H), C1-4alkyleneOC1-4alkylene(CO2H), N(R2xaa)C1- 4alkylene(CO2H), C1-4alkylene(NR2xabR2xac), OC1-4alkylene(NR2xabR2xac) or N(R2xaa)C1- 4alkylene(NR2xabR2xac); wherein said heterocycloalkyl is optionally substituted by 1, 2 or 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1- 4alkoxy, C1-4haloalkyl, halo, CN, OH, NR2xaR2xb, SO2R2xc and NHSO2R2xc; R2xa is selected from H and C1-4alkyl; R2xb is selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R2xc is selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; each R2xaa is independently selected from H and C1-4alkyl; each R2xab is independently selected from H and C1-4alkyl; each R2xac is independently selected from H and C1-4alkyl; or R2xab and R2xac together with the nitrogen atom to which they are attached form a 4-10 membered heterocycloalkyl; R2 is H, halo, C1-4alkyl, C1-4haloalkyl, C1-4alkoxy, C1-4alkyleneOC1-4alkyl, C1- 4alkyleneOC3-6cycloalkyl or C1-4alkyleneO(4-10 membered heterocycloalkyl); each R3is independently halo, C1-4alkyl, C1-4haloalkyl or C1-4alkoxy; m is 0, 1, 2 or 3;wherein group (Ab) is:wherein: R4 is H, C1-4alkyl or C1-4alkylene(aryl); wherein said aryl is optionally substituted by 1, 2 or 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1- 4alkoxy, C1-4haloalkyl, halo, CN, OH, NR4aR4b, SO2R4c and NHSO2R4c; R4a is selected from H and C1-4alkyl; R4b is selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R4c is selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R5 is H or C1-4alkyl; each R6 is independently C1-4alkyl or halo; n is 0, 1, 2 or 3; wherein group (Ac) is:wherein: R7is C1-4alkyl, C1-4alkylene(OH) or C1-4alkyleneOC1-4alkyl; o is 1 or 2; wherein group (Ad) is:wherein: X is a bond, O or CH2; each R8 is independently halo, C1-4alkyl, C1-4alkoxy, OC1-4haloalkyl, OC1-4alkylene(C3- 6cycloalkyl), OC1-4alkylene(4-10 membered heterocycloalkyl) or OH; wherein said heterocycloalkyl and cycloalkyl are optionally substituted by 1, 2 or 3 substituentsindependently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR8aR8b, SO2R8cand NHSO2R8c; R8ais selected from H and C1-4alkyl; R8bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R8cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; each R9is independently halo or C1-4alkyl; p is 0, 1 or 2; q is 0, 1, 2, 3 or 4; wherein group (Ae) is:wherein: R17 is H, halo, C1-4alkyl, C1-4haloalkyl, C1-4alkylene(aryl), C1-4alkylene(OH), C1- 4alkylene(C3-6cycloalkyl), C1-4alkylene(4-10 membered heterocycloalkyl), 4-10 membered heterocycloalkyl, C1-4alkoxy, OC1-4alkylene(aryl), C1-4alkyleneOC1-4alkyl, C1-4alkyleneOC3-6cycloalkyl, C1-4alkyleneO(4-10 membered heterocycloalkyl), C1- 4alkyleneO(aryl), C3-6alkynyl, C1-4alkenylO(C3-6alkynyl), C1-4alkylene(CO2H), OC1- 4alkylene(CO2H), C1-4alkyleneOC1-4alkylene(CO2H), N(R17aa)C1-4alkylene(CO2H), C1- 4alkylene(NR17abR17ac), OC1-4alkylene(NR17abR17ac) or N(R17aa)C1- 4alkylene(NR17abR17ac); wherein said aryl, cycloalkyl or heterocycloalkyl is optionally substituted by 1, 2 or 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR17aR17b, SO2R17c, NHSO2R17c; R17ais selected from H and C1-4alkyl; R17bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R17c is selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; each R17aais independently selected from H and C1-4alkyl; each R17abis independently selected from H and C1-4alkyl; each R17acis independently selected from H and C1-4alkyl; or R17aband R17actogether with the nitrogen atom to which they are attached form a 4-10 membered heterocycloalkyl;R18is H, halo, C1-4alkyl, C1-4haloalkyl, C1-4alkoxy, C1-4alkyleneOC1-4alkyl, C1-4alkyleneOC3-6cycloalkyl or C1-4alkyleneO(4-10 membered heterocycloalkyl); R20is H, halo, C1-4alkyl, C1-4haloalkyl or C1-4alkoxy; R21is H, halo, C1-4alkyl, C1-4haloalkyl or C1-4alkoxy; or; R17is H, halo, C1-4alkyl, C1-4haloalkyl, C1-4alkoxy, C1-4alkyleneOC1-4alkyl, C1-4alkyleneOC3-6cycloalkyl or C1-4alkyleneO(4-10 membered heterocycloalkyl); R18is C1-4haloalkyl, C1-4alkylene(aryl), C1-4alkylene(OH), C1-4alkylene(C3-6cycloalkyl), C1-4alkylene(4-10 membered heterocycloalkyl), 4-10 membered heterocycloalkyl, OC1-4alkylene(aryl), C1-4alkyleneOC1-4alkyl, C1-4alkyleneOC3-6cycloalkyl, C1-4alkyleneO(4-10 membered heterocycloalkyl), C1-4alkyleneO(aryl), C3-6alkynyl, C1-4alkenylO(C3-6alkynyl), C1-4alkylene(CO2H), OC1-4alkylene(CO2H), C1-4alkyleneOC1-4alkylene(CO2H), N(R18aa)C1-4alkylene(CO2H), C1-4alkylene(NR18abR18ac), OC1-4alkylene(NR18abR18ac) or N(R18aa)C1-4alkylene(NR18abR18ac); wherein said aryl, cycloalkyl or heterocycloalkyl is optionally substituted by 1, 2 or 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR18aR18b, SO2R18c, NHSO2R18c; R18a is selected from H and C1-4alkyl; R18b is selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R18c is selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; each R18aa is independently selected from H and C1-4alkyl; each R18ab is independently selected from H and C1-4alkyl; each R18ac is independently selected from H and C1-4alkyl; or R18ab and R18ac together with the nitrogen atom to which they are attached form a 4-10 membered heterocycloalkyl; R20 is H, halo, C1-4alkyl, C1-4haloalkyl or C1-4alkoxy; R21 is H, halo, C1-4alkyl, C1-4haloalkyl or C1-4alkoxy; or; R17 is H, halo, C1-4alkyl, C1-4haloalkyl, C1-4alkoxy, C1-4alkyleneOC1-4alkyl, C1- 4alkyleneOC3-6cycloalkyl or C1-4alkyleneO(4-10 membered heterocycloalkyl); R18 is H, halo, C1-4alkyl, C1-4haloalkyl, C1-4alkoxy, C1-4alkyleneOC1-4alkyl C1- 4alkyleneOC3-6cycloalkyl or C1-4alkyleneO(4-10 membered heterocycloalkyl); R20 is H, halo, C1-4alkyl, C1-4haloalkyl or C1-4alkoxy; R21is C1-4haloalkyl, C1-4alkylene(aryl), C1-4alkylene(OH), C1-4alkylene(C3-6cycloalkyl), C1-4alkylene(4-10 membered heterocycloalkyl), 4-10 membered heterocycloalkyl,OC1-4alkylene(aryl), C1-4alkyleneOC1-4alkyl, C1-4alkyleneOC3-6cycloalkyl, C1-4alkyleneO(4-10 membered heterocycloalkyl), C1-4alkyleneO(aryl), C3-6alkynyl, C1-4alkenylO(C3-6alkynyl), C1-4alkylene(CO2H), OC1-4alkylene(CO2H), C1-4alkyleneOC1-4alkylene(CO2H), N(R21aa)C1-4alkylene(CO2H), C1-4alkylene(NR21abR21ac), OC1-4alkylene(NR21abR21ac) or N(R21aa)C1-4alkylene(NR21abR21ac); wherein said aryl, cycloalkyl or heterocycloalkyl is optionally substituted by 1, 2 or 3 substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR21aR21b, SO2R21c, NHSO2R21c; R21ais selected from H and C1-4alkyl; R21bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R21cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; each R21aais independently selected from H and C1-4alkyl; each R21abis independently selected from H and C1-4alkyl; each R21ac is independently selected from H and C1-4alkyl; or R21ab and R21ac together with the nitrogen atom to which they are attached form a 4-10 membered heterocycloalkyl; wherein B is group (Ba), (Bb) or (Bc): wherein group (Ba) is:wherein: Y is C(R11)(R12), N(R13), O or S; each R10is independently halo or C1-4alkyl; r is 0, 1, 2 or 3; R11 is H or C1-4alkyl; R12 is H or C1-4alkyl; or R11 and R12 together with the carbon atom to which they are attached form a C3-6cycloalkyl; R13is H, C1-4alkyl or C3-6cycloalkyl; wherein said cycloalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR13aR13b, SO2R13cand NHSO2R13c; R13ais selected from H and C1-4alkyl;R13bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R13cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; wherein group (Bb) is:wherein: each R14 is independently halo or C1-4alkyl; s is 0, 1, 2 or 3; wherein group (Bc) is:wherein: R15 is C1-4alkyl, C1-4alkoxy, C3-6cycloalkyl, C1-4haloalkyl, halo or CN; wherein said cycloalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, halo, CN, OH, NR15aR15b, SO2R15cand NHSO2R15c; R15ais selected from H and C1-4alkyl; R15bis selected from H, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R15cis selected from C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-4haloalkyl, aryl and 4-10 membered heterocycloalkyl; R16is H, halo or C1-4alkyl; and D, E and F are each independently C(R16); or one of D, E and F is N, and the two remaining D, E and F groups are independently C(R16); or a pharmaceutically acceptable salt and / or solvate thereof, for use in the prevention ortreatment of a disease, disorder, or condition which is an Other NLRX1-Related Disease,Disorder or Condition .

31. A substance of formula (IV):wherein: R1is H or F; wherein: R2is C1-3alkyl, -CH2OC1-3alkyl, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3-5cycloalkyl; R3is H, C1-3alkyl, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3-5cycloalkyl; R4is H, C1-3alkyl, -CH2OC1-3alkyl, C1-3fluoroalkyl, C1-3alkoxy, C1-3fluoroalkoxy, -CN, halo or C3-5cycloalkyl; and R5 is H, C1-3alkyl, -CH2OC1-3alkyl, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3- 5cycloalkyl; provided that when R5 is H then R1 is F; B is group (Ba) or (Bb): wherein group (Ba) is:wherein: Y is C(R9a)(R9b), O or N(R9c); R9a, R9band R9care independently H or C1-3alkyl or R9aand R9btogether with the carbon atom to which they are attached form a C3-6cycloalkyl group; and R6, R7and R8are independently H, C1-3alkyl, C2-3alkynyl, C1-3fluoroalkyl, C1-3alkoxy, - CN, halo or C3-5cycloalkyl; wherein group (Bb) is:(Bb); wherein: R10 is H, C1-3alkyl, C2-3alkynyl, C1-3fluoroalkyl, C1-3alkoxy, -CN, halo or C3-5cycloalkyl; D is N or C(R11) and R11, R12 and R13 are independently H, C1-3alkyl, C2-3alkynyl, C1-3fluoroalkyl, C1-3alkoxy,-CN, halo or C3-5cycloalkyl; or a prodrug thereof in which an available nitrogen atom in group Ba or Bb is derivatised by the moiety -CH2-OP(=O)(OH)2; or a pharmaceutically acceptable salt and / or solvate thereof, for use in the prevention ortreatment of a disease, disorder, or condition which is an Other NLRX1-Related Disease,Disorder or Condition .

32. A substance of formula (V):wherein: R1is H or C1-4alkyl; R2is H, halo, C1-4alkyl, C1-4haloalkyl; C1-4alkoxy, C1-4haloalkoxy or C0-4alkylene(OH); R3is H, halo or C1-4alkyl; R4is H, halo or C1-4alkyl; R5is halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C2-6alkenyl, C2- 6haloalkenyl, C0-6alkylene(C3-6cycloalkyl), C0-6alkylene(OH); or R4and R5together with the carbon atom to which they are attached form aC5-11 spiro carbocyclyl, 4 to 7 membered heterocycle or C3-6cycloalkyl wherein said spiro carbocyclyl,heterocycloalkyl or cycloalkyl may be optionally substituted by one or more groups selected from C1-3alkyl, C1-3haloalkyl and halo; R6is H or C1-4alkyl; R7is H, halo, C1-4alkyl, C1-4haloalkyl, C1-4alkoxy or C1-4haloalkoxy; A is a monocyclic or bicyclic aryl or a monocyclic or bicyclic heteroaryl optionally substituted by one or more A1; A1is independently selected from the group consisting of: C1-3alkylthio, halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C3-6cycloalkyl, CN, OH, NRgRh, or NHSO2Rj; Rgis H or C1-4alkyl; Rhis H or C1-4alkyl; Rjis C1-4alkyl; or when A represents phenyl substituted by one or more A1, R5together with a substituent A1in the ortho position are joined and together represent (CH2)vwherein v represents 1, 2 or 3 and wherein one of the said CH2groups may optionally be replaced by O;B is a monocyclic or bicyclic heterocycle or a monocyclic or bicyclic heteroaryl wherein said heterocycle or heteroaryl may be optionally substituted by one or more B1; B1is halo, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, oxo (=O), or thiooxo (=S), C0-6alkylene(OH); or a salt and / or solvate thereof,for use in the prevention or treatment of a disease, disorder, or condition which is an OtherNLRX1-Related Disease, Disorder or Condition.

33. A substance of formula (VI):wherein: R1ais H or C1-4alkyl; R1bis H or C1-4alkyl; R2ais H, halo, C1-4alkyl or C1-4haloalkyl; R3ais H, halo or C1-4alkyl; R4ais H or C1-4alkyl; R5ais H, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C2-6alkenyl, C2- 6haloalkenyl, C0-6alkylene(C3-6cycloalkyl), C0-6alkylene(OH); or R4aand R5atogether with the carbon atom to which they are attached form a C3-6cycloalkyl wherein said cycloalkyl may be optionally substituted by one or more groups selected from C1- 4alkyl, C1-4haloalkyl and halo; R6ais H, halo, C1-4alkyl, C1-4haloalkyl, C1-4alkoxy or C1-4haloalkoxy; x is 0, 1 or 2; AA is a phenyl or phenyl fused to C5-6cycloalkyl, wherein said phenyl or phenyl fused to C5-6cycloalkyl may be optionally substituted by one or more AA1; AA1is halo, C2-6alkynyl, C1-6alkyl C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C3-6cycloalkyl, CN, OH, NRqRr, or NHSO2Rt; Rqis H or C1-4alkyl; Rris H or C1-4alkyl; Rtis C1-4alkyl;BA is a monocyclic or bicyclic heterocycle or a monocyclic or bicyclic heteroaryl, wherein said heterocycle or heteroaryl may be optionally substituted by one or more B1A; and B1Ais halo, C1-6alkyl, C1-6haloalkyl, oxo (=O), C1-6alkoxy, C1-6haloalkoxy, or C0-6alkylene(OH); or a salt and / or solvate thereof; for use in the prevention or treatment of a disease, disorder, or condition which is an Other NLRX1-Related Disease, Disorder or Condition.

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