45 results about "Mitochondrial Disorders" patented technology

The present disclosure provides pharmaceutical and nutritional compositions and methods for treating mitochondrial disorders. The present invention relates to a pharmaceutical or nutritional composition comprising a stabilized sulforaphene (e.g., a sulforaphene-cyclodextrin complex) that improves the efficacy, biological activity, and stability of the isolated sulforaphene. The disclosure also includes the use of the stabilized sulforaphene as an effective therapeutic agent for the treatment of mitochondrial disorders, such as mitochondrial myopathy.

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 relates to a method of treating a mitochondrial disease in a patient in need thereof by administering Compound (I), a stimulator of soluble guanylate cyclase (sGC) at certain dosages either alone or in combination therapy.

The present disclosure relates to the use of stimulators of soluble guanylate cyclase (sGC), pharmaceutically acceptable salts thereof, and pharmaceutical preparations or dosage forms containing them, alone or in combination with one or more additional agents, for the treatment of various mitochondrial diseases, in which increased sGC stimulation, or increased concentrations of nitric oxide (NO) or cyclic guanosine 3',5'-monophosphate (cGMP), or both, or upregulation of the NO-sGC-cGMP pathway is desired. Compounds useful in the methods of the present invention are of Formula I or pharmaceutically acceptable salts thereof:

Methods of treating diseases and disorders treatable by AMPK activation with sephin1 and related compounds, for example metabolic syndrome, non-alcoholic fatty liver disease, nonalcoholic steatohepatitis (NASH), obesity, type 2 diabetes, insulin resistance, glucose intolerance, chronic pain, sarcopenia, a neuromuscular disorder, heart failure, cardiac hypertrophy, diabetic cardiomyopathy, cardiac reperfusion injury, chronic kidney disease, polycystic kidney disease, diabetic nephropathy, cardiovascular diseases, inflammatory bowel disease, arthritis, hypertension, peripheral vascular disease, nephrogenic diabetes insipidus, glaucoma, an eye disease or disorder, ocular neovascularization, β-hemoglobinopathy, cancer, fibrosis, cancer cachexia, and mitochondrial disease.

The invention relates to combination or composition comprising: (i) nicotinic acid or a derivative thereof, and (ii) a fatty acid or a derivative thereof selected from tetradecylthioacetic acid 5 (TTA) or a derivative thereof. The invention further relates to a pharmaceutical or nutritional combination or composition for use in a method of preventing or treating mitochondrial diseases, inflammatory diseases, metabolic disorders, neurodegenerative diseases and / or aging of an animal, and / or a method of increasing brain metabolism of an animal, wherein said pharmaceutical or nutritional 10 combination or composition is administered to said animal, and wherein said pharmaceutical or nutritional combination or composition comprises: (i) nicotinic acid or a derivative thereof, and (ii) a fatty acid or a derivative thereof selected from tetradecylthioacetic acid (TTA) or a derivative thereof.

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.

Methods and systems are provided for analyzing the ability of immune cells to kill target cells based on the effectiveness of mitochondria of the immune cells. The systems and methods further can be used for transplanting healthy mitochondria into immune cells to increase their effectiveness against target cells. The methods described herein can be used in treatment of cancer, mitochondrial diseases, and certain metabolic diseases.

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.

Compositions and methods for modulation by upregulation (up modulation) and / or downregulation (down modulation) of mitophagy are described for the treatment of mitochondrial disorders including OPA-1 related disease and Single Large Scale Mitochondrial DNA Deletion (SLSMD). Also disclosed are a number of screening assays and gene targets having utility for the identification of agents which modulate the phenotype associated with such disorders.

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).

To provide: compositions of cells with mitochondrial DNA reduction and / or mitochondrial DNA replacement; methods for producing the same; and methods for treating various diseases associated with genetic or age-related mitochondrial dysfunction.SOLUTION: A method for producing mitochondria replaced cells includes: (a) contacting recipient cells with an agent that reduces endogenous mtDNA copy number; (b) incubating the recipient cells for a period of time sufficient for the agent to partially reduce the endogenous mtDNA copy number in the recipient cells; and (c) co-incubating (1) the recipient cells from the step (b) in which the endogenous mtDNA has been partially reduced with (2) exogenous mitochondria from a healthy donor for a period of time sufficient to non-invasively transfer the exogenous mitochondria into the recipient cells, thereby producing the mitochondria replaced cells.SELECTED DRAWING: Figure 1A

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.

The present disclosure provides pharmaceutical and nutraceutical compositions and methods for the treatment of mitochondrial disorders. The pharmaceutical or nutraceutical compositions include a stabilized sulforaphene, such as sulforaphene-cyclodextrin complex, that increases the efficacy, biological activity and stability of isolated sulforaphene. The present disclosure also includes the use of stabilized sulforaphene as an effective therapeutic agent for the treatment of mitochondrial disorders, such as mitochondrial myopathy.

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.

Polypeptides having a mitochondrial targeting sequence (MTS), an endonuclease sequence, and a destabilization domain sequence; nucleic acids encoding the same; uses of the polypeptides and nucleic acids to induce mitophagy, increase mitochondrial turnover, and / or induce double-strand breaks in mitochondrial DNA in cells; and the aforementioned therapeutic uses, for example, in the treatment of mitochondrial diseases and disorders.

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.

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.