Title:
INHIBITORS OF THE FATTY ACID OXIDATION FOR PROPHYLAXIS AND TREATMENT OF DISEASES RELATED TO MITOCHONDRIAL DYSFUNCTION
Document Type and Number:
WIPO Patent Application WO2003037323
Kind Code:
A3
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 Carnitin-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-substitued oxirane carboxylic acid.
Inventors:
HENKEL THOMAS (DE)
REHFUESS CHRISTOPH (DE)
REHFUESS CHRISTOPH (DE)
Application Number:
PCT/EP2002/011913
Publication Date:
October 23, 2003
Filing Date:
October 24, 2002
Export Citation:
Assignee:
MEDIGENE AG GES FUER MOLEKULAR (DE)
HENKEL THOMAS (DE)
REHFUESS CHRISTOPH (DE)
HENKEL THOMAS (DE)
REHFUESS CHRISTOPH (DE)
International Classes:
A61K31/336; A61K31/4025; A61K31/435; A61K31/443; A61K31/495; (IPC1-7): A61K31/336; A61K31/435; A61K31/495; A61K31/197
Domestic Patent References:
| WO1997000678A1 | 1997-01-09 | |||
| WO2001034145A1 | 2001-05-17 | |||
| WO1998000422A1 | 1998-01-08 |
Foreign References:
| EP0533579B1 | 1996-12-04 |
Other References:
BALTALARLI A ET AL: "Cerebral protection with trimetazidine in transient brain ischemia in rats", INTERNATIONAL JOURNAL OF ANGIOLOGY, vol. 9, no. 3, 2000, ISSN 1061-1711, pages 183 - 187, XP001135219
SUZER T ET AL: "Lipid peroxidation and glutathione levels after cortical injection of ferric chloride in rats: Effect of trimetazidine and deferoxamine.", RESEARCH IN EXPERIMENTAL MEDICINE., vol. 199, no. 4, February 2000 (2000-02-01), pages 223 - 229, XP001145591, ISSN: 0300-9130
HAGUENAUER J P ET AL: "[Trimetazidine and degenerative deafness. Effect on hearing and integration]", ANNALES D'OTO-LARYNGOLOGIE ET DE CHIRURGIE CERVICO FACIALE: BULLETIN DE LA SOCIETE D'OTO-LARYNGOLOGIE DES HOPITAUX DE PARIS. FRANCE 1990, vol. 107 Suppl 1, 1990, pages 51 - 56, XP009005396, ISSN: 0003-438X
COYAS A: "[The efficacy of trimetazidine in cochleovestibular disorders of ischemic origin. A crossover control versus placebo trial]", ANNALES D'OTO-LARYNGOLOGIE ET DE CHIRURGIE CERVICO FACIALE: BULLETIN DE LA SOCIETE D'OTO-LARYNGOLOGIE DES HOPITAUX DE PARIS. FRANCE 1990, vol. 107 Suppl 1, 1990, pages 82 - 87, XP009005395, ISSN: 0003-438X
OSTRE C ET AL: "Electroretinogram in children with mitochondrial encephalomyopathy.", NEUROPHYSIOLOGIE CLINIQUE, vol. 22, no. SUPPL. 1, 1992, 6th European Congress of Clinical Neurophysiology, Lisbon, Portugal, September 19-22, 1992. NEUROPHYSIOL CLIN, pages 95S, XP009005398, ISSN: 0987-7053
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1986, DOGEN H ET AL: "THE USEFULNESS OF TRIMETAZIDINE HYDROCHLORIDE PROSTAGLANDIN E-1 AND ALDOSE REDUCTASE INHIBITOR ONO-2235 IN DIABETIC NEUROPATHY", XP001135229, Database accession no. PREV198682057140
GRANGIER R ET AL: "Neuropathie optique hereditaire de Leber. Mutations de Wallace du genome mitochondrial", BULLETIN DES SOCIETES D'OPHTALMOLOGIE DE FRANCE, (1995),, vol. 95, no. 6, ISSN: 0081-1270, pages 413 - 417, XP009005456
KENNEDY JENNIFER A ET AL: "Effect of perhexiline and oxfenicine on myocardial function and metabolism during low-flow ischemia/reperfusion in the isolated rat heart.", JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, vol. 36, no. 6, December 2000 (2000-12-01), pages 794 - 801, XP009005373, ISSN: 0160-2446
ALLELY M C ET AL: "Modulation of alpha-1-adrenoceptors in rat left ventricle by ischaemia and acyl carnitines: Protection by ranolazine.", JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, vol. 21, no. 6, 1993, pages 869 - 873, XP009005375, ISSN: 0160-2446
SUZER T ET AL: "Lipid peroxidation and glutathione levels after cortical injection of ferric chloride in rats: Effect of trimetazidine and deferoxamine.", RESEARCH IN EXPERIMENTAL MEDICINE., vol. 199, no. 4, February 2000 (2000-02-01), pages 223 - 229, XP001145591, ISSN: 0300-9130
HAGUENAUER J P ET AL: "[Trimetazidine and degenerative deafness. Effect on hearing and integration]", ANNALES D'OTO-LARYNGOLOGIE ET DE CHIRURGIE CERVICO FACIALE: BULLETIN DE LA SOCIETE D'OTO-LARYNGOLOGIE DES HOPITAUX DE PARIS. FRANCE 1990, vol. 107 Suppl 1, 1990, pages 51 - 56, XP009005396, ISSN: 0003-438X
COYAS A: "[The efficacy of trimetazidine in cochleovestibular disorders of ischemic origin. A crossover control versus placebo trial]", ANNALES D'OTO-LARYNGOLOGIE ET DE CHIRURGIE CERVICO FACIALE: BULLETIN DE LA SOCIETE D'OTO-LARYNGOLOGIE DES HOPITAUX DE PARIS. FRANCE 1990, vol. 107 Suppl 1, 1990, pages 82 - 87, XP009005395, ISSN: 0003-438X
OSTRE C ET AL: "Electroretinogram in children with mitochondrial encephalomyopathy.", NEUROPHYSIOLOGIE CLINIQUE, vol. 22, no. SUPPL. 1, 1992, 6th European Congress of Clinical Neurophysiology, Lisbon, Portugal, September 19-22, 1992. NEUROPHYSIOL CLIN, pages 95S, XP009005398, ISSN: 0987-7053
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1986, DOGEN H ET AL: "THE USEFULNESS OF TRIMETAZIDINE HYDROCHLORIDE PROSTAGLANDIN E-1 AND ALDOSE REDUCTASE INHIBITOR ONO-2235 IN DIABETIC NEUROPATHY", XP001135229, Database accession no. PREV198682057140
GRANGIER R ET AL: "Neuropathie optique hereditaire de Leber. Mutations de Wallace du genome mitochondrial", BULLETIN DES SOCIETES D'OPHTALMOLOGIE DE FRANCE, (1995),, vol. 95, no. 6, ISSN: 0081-1270, pages 413 - 417, XP009005456
KENNEDY JENNIFER A ET AL: "Effect of perhexiline and oxfenicine on myocardial function and metabolism during low-flow ischemia/reperfusion in the isolated rat heart.", JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, vol. 36, no. 6, December 2000 (2000-12-01), pages 794 - 801, XP009005373, ISSN: 0160-2446
ALLELY M C ET AL: "Modulation of alpha-1-adrenoceptors in rat left ventricle by ischaemia and acyl carnitines: Protection by ranolazine.", JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, vol. 21, no. 6, 1993, pages 869 - 873, XP009005375, ISSN: 0160-2446
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