42 results about "Frontotemporal dementia" patented technology

The present invention is in the field of transactive response DNA binding protein with a molecular weight of 43 kDa (TARDB or also TDP-43). The invention relates to humanized TDP-43 specific binding molecules, in particular to humanized anti-TDP-43 antibodies or antigen-binding fragment or a derivative thereof and uses thereof. The present invention provides means and methods to diagnose, prevent, alleviate and / or treat a disease, disorder and / or abnormality associated with TDP-43 aggregates including but not limited to Frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Chronic Traumatic Encephalopathy (CTE), and limbic-predominant age-related TDP-43 encephalopathy (LATE).

Disclosed are compounds, and corresponding methods of treatment, that activate myocyte-specific enhancer factor 2 (MEF2) transcriptional activity that are therefore useful in treating deficits in MEF2C activity found in autism spectrum disorder (ASD), intellectual disability (ID), attention deficit and hyperactivity disorder (ADHD), and in diseases characterized by cognitive decline such as Alzheimer's disease (AD), Lewy body dementia (LED), Frontotemporal dementia (FTD), and other forms of dementia, as well as movement disorders such as Parkinson's disease (PD) and parkinsonism from other causes.

Examples may provide a method of determining a neurological disorder status of a subject. The method includes generating at least one dynamic brain network model (DNM) for the subject, and determining at least one sink index (SI) for the subject using the DNM. The method also includes determining whether the subject has frontotemporal dementia (FTD), Alzheimer's disease, or does not have dementia using one or more SI ratios of brain regions associated with FTD to other brain regions. Additional methods as well as related systems and computer readable media are also provided.

The application relates to fused pyrimidinone derivatives of the general formula (I) which act as agonists of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) useful for the treatment of Parkinson's disease, rheumatoid arthritis, Alzheimer's disease, amyotrophic lateral sclerosis, Nasu-Hakola disease, frontotemporal dementia, multiple sclerosis, prion disease, and stroke.

The invention relates to anti-TDP-43 binding molecules and uses thereof. The present invention is in the field of trans-activation responsive DNA binding proteins (TARDB or also referred to as TDP-43) having a molecular weight of 43 kDa. The present invention relates to TDP-43 specific binding molecules, in particular to anti-TDP-43 antibodies or antigen binding fragments or derivatives thereof, and uses thereof. The present invention provides means and methods for diagnosing, preventing, ameliorating and / or treating diseases, disorders and / or abnormalities associated with TDP-43 aggregates, including, but not limited to, frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), chronic traumatic encephalopathy (CTE), and edge-dominant age-related TDP-43 encephalopathy (LATE).

In various aspects of the present disclosure, there is provided a method of detecting, preventing, reversing, treating, or delaying the onset of a nervous system disease (e.g., an adult onset nervous system disease, Alzheimer's disease, Parkinson's disease, frontotemporal dementia).

The present disclosure relates to a compound of formula (I) which is in crystalline Form 1, characterized by having a powder X-ray diffractogram displaying peaks expressed as degree 2-Theta angles at about 3.3, 10.0, 20.1, 21.7, and 25.0. The present disclosure also relates to processes for its preparation, as well as a medicament and a pharmaceutical composition comprising it. The present disclosure further concerns the crystalline Form 1 of compound of formula (I) for use as a medicine and more particularly in the prevention and / or in the treatment of Parkinson's disease, frontotemporal dementia, multiple system atrophy, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, or brain injury.

The present invention relates to antisense oligonucleotides capable of modulating the expression of Tau in a target cell. The oligonucleotide lines hybridize to the MAPT mRNA. The present invention further relates to conjugates of the oligonucleotides, and pharmaceutical compositions and methods for the treatment of a Tau aberrant deposition lesion (Tauopathy), Alzheimer's disease (AD), frontotemporal dementia (FTD), FTDP-17, progressive ocular nuclear paralysis (PSP), chronic traumatic brain lesion (CTE), corticobasal nuclear degeneration (CBD), epilepsy, a Display syndrome, depression, a seizure disorder (disorder of epileptic seizure), and a movement disorder (disorder of movement).

The present disclosure relates to the novel use of ANAVEX3-71 and related compounds in medical treatments, such as Parkinson's Disease, Frontotemporal Dementia, Schizophrenia, and Alzheimer's Disease.

The present invention relates to novel compounds and pharmaceutical compositions. More particularly, the present invention provides novel compounds which are useful for the treatment of and prevention of neurodegenerative disorders including, but not limited to, Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD), and Nasu-Hakola Disease (NHD).

The present disclosure provides for a compound according to formula (I)or a pharmaceutically acceptable salt thereof as CaV1.22 activators for the treatment of schizophrenia, bipolar disorder, major depressive disorder, substance use disorder, ADHD, Phelan-McDermid Syndrome, autism spectrum disorder, multiple sclerosis, frontotemporal dementia, Alzheimer's disease, Brugada Syndrome, Short QT syndrome, or early repolarization syndrome.

The present invention belongs to the field of transactivation-responsive DNA binding protein with a molecular weight of 43 kDa (TARDB or also known as TDP-43). The present invention relates to TDP-43 specific binding molecules, in particular anti-TDP-43 antibodies or antigen-binding fragments or derivatives thereof and their uses. The present invention provides means and methods for diagnosing, preventing, alleviating and / or treating diseases, disorders and / or abnormalities associated with TDP-43 aggregates, including but not limited to frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), chronic traumatic encephalopathy (CTE) and limbic-dominant age-related TDP-43 encephalopathy (LATE).

The present invention is in the field of trans-activation responsive DNA binding proteins (TARDB or also referred to as TDP-43) having a molecular weight of 43 kDa. The present invention relates to TDP-43 specific binding molecules, in particular to anti-TDP-43 antibodies or antigen binding fragments or derivatives thereof, and uses thereof. The present invention provides means and methods for diagnosing, preventing, ameliorating, and / or treating diseases, disorders, and / or abnormalities associated with TDP-43 aggregates, including, but not limited to, frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), chronic traumatic encephalopathy (CTE), and edge dominant age-related TDP-43 encephalopathy (LATE).

Provided herein are fusion proteins that comprise progranulin and an Fc polypeptide. Methods of using such proteins to treat progranulin-associated disorders (e.g., a neurodegenerative disease, such as frontotemporal dementia (FTD)) are also provided herein.

Disclosed are bicyclic heteroarene compounds, including purines, as PIKfyve inhibitors useful in the treatment of a TDP-43-associated neurological / neurodegenerative disorder, such as frontotemporal dementia, ALS and Alzheimer's disease. The compounds described herein, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing such neurological / neurodegenerative diseases.

There is described a set of antisense oligonucleotides suitable for inducing exon skipping on a pre-mature RNA transcript (pre-mRNA) from a human Granulin gene (GRN) carrying a null mutation. There are further described a pharmaceutical composition comprising said set of antisense oligonucleotides and the therapeutic use of said oligo set and / or pharmaceutical composition, particularly for the prevention and / or therapeutic treatment of a neurodegenerative disease such as frontotemporal dementia (FTD).

The present disclosure relates, in some aspects, to compositions of UNC13A antisense oligonucleotides (ASOs) and methods of using ASO to alter UNC13A concealment exon splicing and increase UNC13A protein expression. Such ASO may be used in the treatment of neurodegenerative disorders, in particular neurodegenerative disorders associated with the TAR-DNA binding protein-43 (TDP-43) pathology, such as amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD).

Among the various aspects of the present disclosure is the provision of a method of detecting, preventing, reversing, treating, or delaying the onset of a neurological disease (e.g., adult-onset neurological diseases, Alzheimer's disease, Parkinson's disease, Frontotemporal dementia).

The application relates to fused pyrimidinone derivatives of the general formula (I) which act as agonists of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) useful for the treatment of Parkinson's disease, rheumatoid arthritis, Alzheimer's disease, amyotrophic lateral sclerosis, Nasu-Hakola disease, frontotemporal dementia, multiple sclerosis, prion disease, and stroke.

The present disclosure relates to a compound of formula (I) which is in crystalline Form 1, characterized by having a powder X-ray diffractogram displaying peaks expressed as degree 2-Theta angles at about 3.4, 6.8, 10.3, 13.7, and 20.5. The present disclosure also relates to processes for its preparation, as well as a medicament and a pharmaceutical composition comprising it. The present disclosure further concerns the crystalline Form 1 of compound of formula (I) for use as a medicine and more particularly in the prevention and / or in the treatment of Parkinson's disease, frontotemporal dementia, multiple system atrophy, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, or brain injury.

Disclosed herein are UNC13A oligonucleotides having one or more spacer regions or having no spacer regions. In various embodiments, UNC13A oligonucleotides with spacer regions can reduce misspliced UNC13A transcripts and increase full-length UNC13A transcripts, resulting in therapeutic efficacy on nervous system diseases such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), or Alzheimer's disease (AD).

Disclosed are compounds of Formulas (I), (la), (lb), (II), (Ila), (III), (Illa), and (Illb), as well as pharmaceutical compositions thereof. The compounds can be used to improve proteostasis and enhance clearance of protein accumulation events by positively modulating the autophagy-lysosomal pathway, including augmenting the activity of cathepsin enzymes, and / or to treat neurological diseases, disorders and conditions, such as, but not limited to, Alzheimer's disease, Parkinson's disease, Huntington's disease, mild cognitive impairment, frontotemporal dementia, amyotrophic lateral sclerosis, Lewy body dementias, chronic traumatic encephalopathy, traumatic brain injury, and α-synucleinopathies.

Among the various aspects of the present disclosure is the provision of a method of detecting, preventing, reversing, treating, or delaying the onset of a neurological disease (e.g., adult-onset neurological diseases, Alzheimers disease, Parkinsons disease, Frontotemporal dementia).

Disclosed are compounds of Formulas (I), (Ia), (Ib), (II), (IIa), (III), (IIIa), and (IIIb), as well as pharmaceutical compositions thereof. The compounds can be used to improve proteostasis and enhance clearance of protein accumulation events by positively modulating the autophagy-lysosomal pathway, including augmenting the activity of cathepsin enzymes, and / or to treat neurological diseases, disorders and conditions, such as, but not limited to, Alzheimer's disease, Parkinson's disease, Huntington's disease, mild cognitive impairment, frontotemporal dementia, amyotrophic lateral sclerosis, Lewy body dementias, chronic traumatic encephalopathy, traumatic brain injury, and α-synucleinopathies.

The present invention provides a formulation of metformin and glibenclamide for the prevention and / or treatment of neurodegenerative diseases, preferably chosen among Parkinson's disease, multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal dementia, Lewy body dementia, Huntington's disease and Alzheimer's disease.

Novel compounds such as DHMP maintain DHM features and pharmacological activities with increased potency and efficacy, improved water solubility, enhanced bioavailability, increased permeability to the blood brain barrier (BBB), and increased stability. Because DHMP retains the therapeutic activities of DHM and has properties that improve its bioavailability, it can be used as a therapeutic agent for treating Alzheimer's disease-related diseases (ADRD) including Alzheimer's disease (AD), Vascular Dementia, Frontotemporal Dementia (FTD), Mixed Dementia as well as neurodegeneration such as Parkinson's disease. Administration of these compounds result in beneficial pathological changes including reduction of Aꞵ and Tau, improvement of neuroinflammation, reduction of cognitive / memory deficits, as well as improvement of anxiety, depression, and aggression. The disclosed DHM derivatives can also be used to treat sleep disorders, neurological disorders such as PTSD, Autism, Epilepsy / Seizures, and Alcohol Use Disorders (AUD), fetal alcohol syndrome (FAD), substance addictions, and cancers.

Aspects of the disclosure relate to methods and compositions (e.g., kits) for detecting repeat-associated non-ATG (RAN) proteins in a subject (e.g., a subject having or suspected of having a disease associated with RAN protein translation, for example amyotrophic lateral sclerosis (ALS) and / or frontotemporal dementia (FTD), or spinocerebellar ataxia type 36 (SCA36), or other diseases that produce poly(PR), poly(GR) or poly(GP) RAN proteins. In some embodiments, methods described by the disclosure comprise detecting one or more RAN proteins in a biological sample obtained from a subject by an electrochemiluminescence-based immunoassay using one or more anti-RAN protein antibodies. In some embodiments, the disclosure relates to kits comprising one or more anti-RAN antibodies and an electrochemiluminescence-based immunoassay plate and / or reagents.

The present disclosure describes that the 15-lipoxygenase (15-LO) product 4-hydroxynonenal (4HNE or 4-HNE) post-translationally modifies LRRK2 and is believed to induce a pathologically elevated, chronic LRRK2 kinase activity associated with a LRRK2 mediated disease or condition, e.g., Parkinson's disease or frontotemporal dementia. Production of LRRK2-4HNE adducts, e.g., LRRK2 Cys2024-4HNE and / or LRRK2 Cys2025-4HNE adduct described herein, may be an indication of a LRRK2 mediated disease or condition. Inhibiting the production of excessive 4HNE in cells by 15-LO inhibitors converted an elevated LRRK2 activity to a normal basal LRRK2 activity level as demonstrated in cellular experiments in the Examples. The 15-LO inhibition of 4HNE production is believed to only remove elevated LRRK2 activity associated with LRRK2 mediated diseases or conditions and not normal LRRK2 activity that may be required for other cellular functions. Accordingly, 15-LO inhibition of elevated LRRK2 activity and / or expression may afford a safe and effective treatment for LRRK2 mediated diseases or conditions.

In various aspects of the present disclosure, a method is provided for detecting, preventing, reversing, treating, or delaying the onset of a neurological disease (e.g., an adult-onset neurological disease, Alzheimer's disease, Parkinson's disease, frontotemporal dementia).