61 results about "Mitochondrial Disorders" patented technology

The invention belongs to the technical field of biomedicine, and discloses an immortalized cell line for human kidney suspected cell carcinoma as well as a culture method and application of the immortalized cell line. The immortalized cell line for the human kidney suspected cell carcinoma, disclosed by the invention, is named as a human kidney suspected cell carcinoma cell line Loya a-710 (Homo sapiens), the classification name of the Latin name of the immortalized cell line is Chromophore sensor cell carcino: Loya a-710, and the preservation number of the immortalized cell line is CCTCC (China Center for Type Culture Collection) NO: C2025123. The human kidney suspected cell carcinoma cell line Loya-710 disclosed by the invention is used as an in-vitro model to rapidly grow in tissue culture, and mitochondrial mutation characteristics, a vesicle structure and a classical immunohistochemical marker of ChRCC are reserved. The invention provides a precious tool for further research on ChRCC heredity, molecules and biological characteristics, and also provides a powerful new model for mitochondrial diseases.

The present invention 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 sGC stimulation is increased, or the concentration of nitric oxide (NO) or cyclic 3 ', 5'-guanosine monophosphate (cGMP), or both, is increased, or both, or both. Or an up-regulation of the NO-sGC-cGMP pathway is desirable. Compounds useful in the methods of the invention are compounds of Formula I or pharmaceutically acceptable salts thereof.

The ageing of the population is a key issue in the modern societies. The inventors have therefore searched how to determine parameters linked with the biological age of the subject. This has led them to find that characterizing mitochondria in an area of the subject enables to deduce such parameters. For this, the inventors has developed a tool providing with characterizing parameters of a mitochondrion, and notably a morphology parameter of the mitochondrion and an ultrastructure parameter of the mitochondrion. This opens the way of exploiting the characterizing parameters of mitochondria for multiples applications, such as therapy, medicine screening or clinical follow-up for aging related disorders or mitochondrial disorders.

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.

This invention relates to compounds of the formula (1) or a salt or tautomer thereof; wherein: R1 is C(O)ORa; Ra is selected from hydrogen, an optionally substituted methyl or C2-12 hydrocarbyl group and a group A-B-Cyc; A is selected from a bond and a C1-6 alkylene linker group; B is absent, -C(O)NRD- or -NRDC(O)-, provided that when A is a bond, B is absent; RD is selected from hydrogen and a C1-4 hydrocarbyl group; Cyc is an optionally substituted 5-6 membered cyclic aromatic group or 3-6 membered cyclic non-aromatic group R2 is selected from hydrogen, an optionally substituted C1-4 hydrocarbyl group, and optionally substituted 5-6 membered cyclic aromatic groups or 3-6 membered cyclic non-aromatic groups; one of R3 and R4 is selected from hydrogen and an optionally substituted C1-4 hydrocarbyl group; and the other of R3 and R4 is hydrogen. The compounds increase mitochondrial function and the invention therefore also provides pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds, in particular in diseases caused or affected by mitochondrial dysfunction.

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 disclosure is directed to nitrogen-containing heteroaryl analogs, methods of making nitrogen-containing analogs, and methods of treating disorders associated with PINK1 kinase activity including, but not limited to, neurodegenerative diseases, mitochondrial diseases, fibrosis, and / or cardiomyopathy using these analogs. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

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.

The present disclosure is directed to N-(3-substituted-chroman-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine compounds, methods of making N-(3-substituted-chroman-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine compounds, and methods of treating disorders associated with PINK1 kinase activity including, but not limited to, neurodegenerative diseases, mitochondrial diseases, fibrosis, and / or cardiomyopathy using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

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

The present disclosure describes fused quinone compounds, and compositions and methods thereof. Such compounds can be useful in treating mitochondrial diseases in a subject, such as a human.

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.

The invention belongs to the technical field of gene detection, and particularly relates to a mitochondrial DNA highly pathogenic mutation detection kit based on digital PCR and a detection method. The kit comprises a primer pair for amplifying the high pathogenic mutation of the mitochondrial DNA, a probe and a digital PCR (Polymerase Chain Reaction) premixed solution. The invention provides the primer pair for amplifying the high pathogenic mutation of the mitochondrial DNA and a probe sequence. Detection primers and probes are respectively provided for 14 Chinese common pathogenic mitochondrial DNA variations, about 20 primary mitochondrial DNA diseases can be screened through detection, the detection kit provided by the invention has the characteristics of accuracy, sensitivity and economy, the detection sensitivity is improved to 0.01% of mutation load by optimizing the primer probe design and an amplification system, and the detection kit can be used for detecting the primary mitochondrial DNA diseases of the primary mitochondrial DNA diseases of the primary mitochondrial DNA diseases of the primary mitochondrial DNA diseases of the primary mitochondrial DNA diseases of the primary mitochondrial DNA diseases. The detection can be completed within 6 hours, the clinical decision-making period is greatly shortened, and the kit can be suitable for the fields of conventional screening of mitochondrial DNA diseases, prenatal diagnosis, genetic detection before embryo implantation and the like.

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.