Inhibitors of Fatty Acid Oxidation for Prophylaxis and Treatment of Diseases Related to Mitochondrial Dysfunction
AssigneeMediGene AG
InventorsThomas Henkel, Christoph Rehfuess
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Abstract
Described are a method and a composition for preventing and/or treating a disease related to mitochondrial dysfunction by inhibiting the fatty acid oxidation of one or more cells of an organism. Particularly, the fatty acid oxidation is inhibited by inhibiting the expression and/or activity of the enzyme Camitin-Palmitoyl-Transferase-1 (CPT-1) by means of an arylalkyl- or arlyoxyalkyl-substitued oxirane carboxylic acid or pharmaceutically acceptable salts and derivatives of the arylalkyl-substituted oxirane carboxylic acid.
Claims43
A method for preventing and/or treating a disease related to mitochondrial dysfunction by inhibiting the fatty acid oxidation of one or more cells of an organism.
The method according to one of the preceding claims, wherein the disease related to mitochondrial dysfunction is Morbus Alzheimer, Morbus Parkinson, amyotrophic lateral sclerosis, inflammatory diseases, acute traumatic events such as surgery or injury, AIDS related wasting due to the toxicity of reverse transcriptase inhibitors, mitochondrial myopathies, senescence and ageing, neuronal ischemia, a polyglutamine disease, dystonia, Leber's heredity optic neuropathy (LHON), schizophrenia, stroke, myodegenerative disorders, Mitochondrial Encephalomyopathy Lactic Acidosis and Strokelike Episodes (MELAS), Myoclonic Epilepsy associated with Ragged-Red Fibers (MERRF), Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP), Progressive External Ophthalmoplegia (PEO), Leigh's disease, Kearns-Sayres Syndromes, muscular dystrophy, myotonic distrophy, chronic fatigue syndrome, Friedreich's Ataxia;
- developmental delay in cognitive, motor, language, executive function or social skills;
- epilepsy, peripheral neuropathy, optic neuropathy, autonomic neuropathy, neurogenic bowel dysfunction, sensorineural deafness, neurogenic bladder dysfunction, migraine;
- renal tubular acidosis, hepatic failure, lactic acidemia, parodontosis, Duchenne muscular dystrophy, Becker's muscular dystrophy, McArdle's disease, abnormities of the testosterone synthesis and/or hypoparathyroidism.
Use of at least one agent inhibiting the fatty acid oxidation for the preparation of a pharmaceutical composition for the prophylaxis and/or treatment of a disease related to mitochondrial dysfunction.
A method to investigate the effect of fatty acid oxidation inhibitors on mitochondrial function in vitro, said method comprising the steps of
- a) cultivating cells under conditions which are essential for mitochondrial survival,
- b) adding of at least one mitochondria damaging agent to induce mitochondrial dysfunction,
- c) adding at least one fatty acid oxidation inhibitor, and
- d) monitoring of the mitochondrial function.
The method according to one of claims 20 to 36, wherein the fatty acid oxidation inhibitors are added to the cultivated cells after the mitochondria damaging agents.
A pharmaceutical composition for the prophylaxis and/or treatment of diseases related to mitochondrial dysfunction, the composition comprising at least one agent inhibiting to the fatty acid oxidation of an organism.
Dependencies are inferred from the claim text.