27 results about "Mitochondrial Disorders" patented technology

Therapeutic combinations, pharmaceutical compositions, and pharmaceutical kits are provided, comprising fungi (e.g., Psilocybe spp.), plants (e.g., Cannabis spp., Dipteryx spp.), and algae (e.g., from the family Bangiaceae, including Pyropia spp. and Porphyra spp.), including extracts thereof and bioactive molecules derived therefrom. Also provided are methods for producing the combinations, compositions, and kits such as through natural, biosynthetic, or synthetic means. Further provided are methods of use for treating medical conditions, particularly mitochondrial and other disorders, wherein the disclosed combinations and compositions exhibit synergistic effects and therapeutic and other advantages.

The present disclosure is in the field of biomedicine and particularly relates to a therapeutic agent for the treatment of mitochondrial disorder and promoting mitochondrial function in a subject. The method comprises administering nucleoside derivative cordycepin CO1, its derivatives and a pharmaceutically acceptable carrier to a subject. Also provided is cordycepin, its derivatives and a pharmaceutical composition thereof.

The invention discloses an NDUFS2 gene heterozygous editing pig as well as a construction method and application thereof, and relates to the field of animal gene engineering and disease model construction. The eighth exon of the NDUFS2 gene of the pig is deleted or mutated, and presents an NDUFS2 heterozygous genotype; in the newborn period, the number of neurons of the middle cerebral cortical layer and the number of dopaminergic neurons are obviously reduced, the number of neurons of the adult cortical layer is continuously reduced along with mitochondrial swelling and crest fracture, and after MPTP treatment, the number of neurons of the adult cortical layer is disordered in motion trail, and the body tremor index is increased. The pig model not only can be used for revealing the action mechanism of the NDUFS2 defect in neurodegenerative diseases (such as Parkinson's disease), but also can be used as an important tool for screening new drugs, evaluating treatment means and researching mitochondrial diseases.

The present invention provides a compound having a PDHK inhibitory activity and useful for the treatment or prophylaxis of diabetes (type 1 diabetes, type 2 diabetes etc.), insulin resistance syndrome, metabolic syndrome, hyperglycemia, hyperlactacidemia, diabetic complications (diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, cataract etc.), cardiac failure (acute cardiac failure, chronic cardiac failure), cardiomyopathy, myocardial ischemia, myocardial infarction, angina pectoris, dyslipidemia, atherosclerosis, peripheral arterial disease, intermittent claudication, chronic obstructive pulmonary disease, brain ischemia, cerebral apoplexy, mitochondrial disease, mitochondrial encephalomyopathy, cancer, pulmonary hypertension or Alzheimer disease. The present invention relates to a compound of the formula [I-a] or the formula [II], or a pharmaceutically acceptable salt thereof:wherein each symbol means the same as that described in the specification.

The invention relates to the technical field of biological medicine, in particular to a recombinant adeno-associated virus and a packaging system and application thereof. An expression cassette of the GTPBP3 gene is inserted into the genome of the recombinant adeno-associated virus. Through the recombinant adeno-associated virus vector, the defects of heart and muscle in protein and function caused by Gtpbp3 mutation can be effectively supplemented safely and stably in a targeting manner, and feasibility exploration of gene therapy on mitochondrial diseases caused by modification enzyme defects is performed for the first time; and a theoretical basis and a method are provided for the treatment of clinical similar mitochondrial diseases.

Provided are methods of treating a Primary Mitochondrial Disorder (PMD) or Mitochondrial DNA Depletion Syndrome (MDDS) in a subject in need thereof comprising: administering a therapeutically effective amount of a compound listed in Table 1, Table 2, Table 3, Table 4, or Table 5. The subject may have one or more mutations or deletions in the DNA polymerase γ gene (POLG).

Methods for treating diseases and disorders treatable by AMPK activation with cefin-1 and related compounds, such as metabolic syndrome, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis (NASH), obesity, type 2 diabetes, insulin resistance, glucose intolerance, chronic pain, muscle loss, neuromuscular disorders, heart failure, cardiac hypertrophy, diabetic cardiomyopathy, cardiac reperfusion injury, chronic kidney disease, polycystic kidney disease, diabetic nephropathy, cardiovascular disease, inflammatory bowel disease, arthritis, hypertension, peripheral vascular disease, nephrogenic diabetes insipidus, glaucoma, eye diseases or disorders, ocular angiogenesis, β-hemochromocytic disorder, cancer, fibrosis, cancer cachexia, and mitochondrial diseases.

The present disclosure relates to the use of stimulators of soluble guanylate cyclase (sGC), pharmaceutically acceptable salts thereof and pharmaceutical formulations or dosage forms comprising them, alone or in combination with one or more additional agents, for the treatment of various mitochondrial diseases, wherein an increase in sGC stimulation, or an increase in the concentration of nitric oxide (NO), or cyclic guanosine 3′,5′-monophosphate (cGMP) or both, or an upregulation of the NO-sGC-cGMP pathway is desirable. Compounds useful in the methods of the invention are those of Formula I or pharmaceutically acceptable salts thereof.

Provided are methods of treating a subject having a Primary Mitochondrial Disorder (PMD) or Mitochondrial DNA Depletion Syndrome (MDDS) comprising administering a therapeutically effective amount of a compound listed in Table 1, Table 2, Table 3, Table 4, or Table 5, wherein the subject does not have a mutation in the DNA polymerase γ gene (POLG).

The invention relates to a mitochondrial delivery system and a preparation method and application thereof. According to the mitochondrial delivery system, safe and efficient cell entry of active mitochondria can be achieved, the mitochondrial delivery system has appropriate particle size and surface potential, toxicity to cells is avoided while the entrapment rate of the mitochondria is effectively improved and the electrochemical stability and biological activity of a mitochondrial membrane are guaranteed, and the mitochondrial cell entry efficiency is remarkably improved. The mitochondrial delivery system not only can transplant active mitochondria into common cells to repair cell damage, but also can transplant the active mitochondria into egg cells to play a role across a zona pellucida and a plasma membrane barrier. The mitochondrial delivery system can be used for treating mitochondrial diseases related to mitochondrial dysfunction, especially infertility caused by mitochondrial dysfunction of egg cells.

A composition for preventing, ameliorating, or treating mitochondrial disorders according to the present invention comprises a peptide consisting of the amino acid sequence of general formula 1: K-Y-R1-R2-R3-R4-R5-R6-R7-R8 (general formula 1), wherein, in general formula 1, R1 is arginine (R), lysine (K), or glutamine (Q); R2 is arginine (R) or glutamine (Q); R3, R4, and R5 are each arginine (R) or lysine (K); R6 is asparagine (N) or serine (S); and R7 and R8 are lysine (K) or tyrosine (Y). The composition according to the present invention can prevent, ameliorate, or treat mitochondrial disorders by reducing oxidative stress caused by increased reactive oxygen species in cells.

Disclosed are a 1-deoxynojirimycin derivative and use thereof. According to the present invention, a variety of 1-deoxynojirimycin derivatives are prepared and obtained through screening. Compared with 1-deoxynojirimycin as a lead compound, the 1-deoxynojirimycin derivative can better bind to an amino acid site that is related to a target protein OPA1, stabilize a binding pocket at a dimer interface, promote the formation of an OPA1 dimer and repair a mitochondrial ultrastructure, thereby significantly saving mitochondrial functions and effectively improving a physiological state of cells. The 1-deoxynojirimycin derivative of the present invention can be used for preparing a drug for treating a disease that is related to unbalanced formation of the OPA1 dimer, and for example, can be used as a potential therapeutic drug for mitochondrial cardiomyopathy and other mitochondrial diseases.

To provide compounds and compositions capable of modulating PINK1 kinase activity, and methods for producing and using the same.SOLUTION: A compound has a structure in the figure. (In the formula: Z is O, NH, or CH2; R1a, R1b, R1c and R1d are H, halogen, CN, NH2, or the like; and R2 is -(CH2)nCy1, -O(CH2)nCy1, Cy1, or the like, where Cy1 is C4-C9 cycloalkyl, C3-C9 heterocycle, or the like.)SELECTED DRAWING: Figure 1A

The present invention is directed to a composition and a method for treating a mammal exhibiting an inherited mitochondrial disease. That method comprises administering a pharmaceutical composition containing a mitochondria-treating effective amount of PEG-OAC nanozymes, DEF-OAC-PEG nanozymes or both nanozymes dissolved or dispersed in a physiologically tolerable diluent. In that composition, PEG is an acronym for a reacted alpha-amino-omega-methoxy-poly(ethylene glycol) substituent, OAC is an acronym for oxidized activated charcoal particle, and DEF is an acronym for a reacted deferoxamine substituent. Both of the PEG and the DEF substituents are each covalently bonded to the OAC particle by the primary amino group on each.

The present invention discloses 1-deoxynojirimycin derivatives and their uses. Through screening, several 1-deoxynojirimycin derivatives were prepared. Compared with the lead compound 1-deoxynojirimycin, these derivatives better bind to the relevant amino acid site of the target protein OPA1 and are stabilized in the binding pocket of the dimer interface. They promote the formation of OPA1 dimers and restore mitochondrial ultrastructure, thereby significantly maintaining mitochondrial function and effectively improving cellular physiological status. The 1-deoxynojirimycin derivatives of the present invention are useful for preparing drugs for treating diseases associated with an imbalance in OPA1 dimer formation, and are promising therapeutic agents for, for example, mitochondrial cardiomyopathy and other mitochondrial diseases.

Disclosed are analogs of elamipretide (MTP-131). The compounds are useful for the treatment and prevention of ischemia-reperfusion injury (e.g., cardiac ischemia-reperfusion injury) or myocardial infarction.

The invention discloses a technology for inducing mitochondrial membrane damage and an autophagy degradation mechanism based on Raptinal. The technology is used for reducing the content of residual mutation mtDNA carried in the mitochondrial replacement process. According to the method, before nuclear transfer (PNT), a nuclear donor embryo containing mutated mtDNA is placed in a Raptinal operating solution for short-time incubation, so that a mutated mitochondrial membrane is depolarized and damaged, and then the mutated mitochondrial membrane is selectively cleared through the mitochondrial autophagy effect of a nuclear receptor embryo, so that the co-transfer of the mutated mtDNA is remarkably reduced. And cell apoptosis is avoided by adding a pan-caspase inhibitor, so that the balance between membrane injury and embryo survival is realized. C57BL / 6J and BALB / c mice are taken as models, allele-specific PCR (polymerase chain reaction) is used for detecting mtDNA residues of reconstructed embryos, and results show that the detection rate of mutated mtDNA can be reduced from 100% to 30% and the carrying rate of the mutated mtDNA is reduced by more than 70% through Raptinal treatment. The method is easy and convenient to operate, safe, reliable and suitable for the mammalian mitochondrial replacement process, and an efficient new scheme is provided for preventing maternal mitochondrial genetic diseases.

The invention discloses adenine deaminase, a mitochondrial base editing system containing the adenine deaminase and application of the adenine deaminase. Compared with an amino acid sequence shown as SEQ ID NO: 2, the adenine deaminase has one or more amino acid residue differences. The adenine deaminase disclosed by the invention is based on TadA structure-oriented molecular modification, has higher deamination efficiency, shows remarkably enhanced editing activity in a cell nucleus base editing system and a mitochondrial base editing system, remarkably improves the efficiency and the targeting range of a traditional CRISPR source ABE and a mitochondrial adenine editor, and can be used for preparing a mitochondrial adenine deaminase. The application in the aspects of mitochondrial disease model preparation, gene therapy, gene function research and the like is greatly promoted.

This disclosure provides a gene transfer construct comprising a destabilization domain (DD) sequence, a translation separator sequence, and a sequence encoding one or more copies of one or more peptides of interest; a nucleic acid encoding the gene transfer construct; the use of a nucleic acid encoding the gene transfer construct to prevent mitochondrial hyperfission and fragmentation; the use of a nucleic acid encoding the gene transfer construct to induce apoptosis in cells, such as cancer cells; and therapeutic applications of a nucleic acid encoding the gene transfer construct, for example, in the treatment of mitochondrial dysfunction and mitochondrial diseases and disorders associated with various types of cancer.

The present invention relates to quinone, hydroquinone and naphthoquinone analogs of vatebenzoquinone for the treatment of mitochondrial disorder diseases. Disclosed is a compound of formula C-D, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, tautomer, hydrate, and / or solvate thereof, where C is 11, and D is 13, 14, 19, or 20. The invention also discloses application of the compound, the pharmaceutically acceptable salt or the composition containing the compound and the pharmaceutically acceptable salt in preparation of medicines for treating or preventing Friedel's Ataxia, improving the expression level of ataxia, treating defects of complex I, reducing or inhibiting the activity of lipoxygenase-15 and reducing or inhibiting ferroptosis, and also discloses application of the compound, the pharmaceutically acceptable salt or the composition containing the compound and the pharmaceutically acceptable salt in preparation of medicines for treating or preventing Friedel's Ataxia, improving the expression level of ataxia, treating defects of complex I.

The present invention provides methods of treating mitochondrial diseases using an active fragment of Activity -Dependent Neurotrophic protein, i.e., NAP (davunetide).

The present invention provides methods and compositions for generation of mitochondria replaced cells (MirC), and therapeutic methods for using such compositions for treating a subject having an age-related disease or syndrome, mitochondrial disease or disorder, or otherwise in need of mitochondrial replacement. Also provided are methods and compositions for producing a recipient cell having a mitochondrial disease or disorder, as well as methods and compositions for producing or enhancing production of an inducible pluripotent stem cell (iPSC). In addition, methods and compositions to enhance mitochondrial transfer are also included.