{"id":20351,"date":"2024-06-27T17:55:50","date_gmt":"2024-06-27T15:55:50","guid":{"rendered":"https:\/\/ela-international.preprod.melisagency.fr\/?post_type=news_research&p=20351"},"modified":"2024-07-09T15:07:39","modified_gmt":"2024-07-09T13:07:39","slug":"epi-743-clinical-trial-in-adrenomyeloneuropathy","status":"publish","type":"news_research","link":"https:\/\/elainternational.eu\/en\/actualites_recherche\/epi-743-clinical-trial-in-adrenomyeloneuropathy\/","title":{"rendered":"EPI-743 clinical trial in adrenomyeloneuropathy"},"content":{"rendered":"\n\n
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EPI-743 clinical trial in adrenomyeloneuropathy<\/strong><\/h3>\n <\/div>\n <\/div>\n<\/section>\n\n\n\n
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Description of the project<\/strong><\/h5>\n <\/div>\n
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X-linked adrenoleukodystrophy (ALD) is the most common peroxisomal disease. The product of the affected gene is a peroxisomal membrane protein (ADLP), a member of the large family of ABC transporters (ATP-binding cassette, ATP binding cassette): ABCD1. The ABCD1 protein-deficient mouse model of X-ALD exhibits lateonset, progressive axonal degeneration resembling AMN in humans. We observe an early onset of oxidative stress accompanied by lesions, one year before the onset of the disease.<\/p>\n

In these mice, treatment with a combination of antioxidants including \u03b1-tocopherol, N-acetyl-cysteine \u200b\u200band \u03b1-lipoic acid reverses oxidative damage, improves energy deficit as well as axonal degeneration and damage. Oxidative stress therefore appears to be underlying axonal degeneration in adrenoleukodystrophy; it is one of the hallmarks of the pathogenesis of X-ALD.<\/p>\n

Our group has helped to demonstrate the glutathione imbalance present in the blood of patients with X-ALD, thus highlighting the importance of imbalance of forms of glutathione (its oxidised form versus its reduced form) as a characteristic and potential biomarker of this disease.<\/p>\n

More recently, a new drug, called EPI-743 (alphatocotrienol quinone), has been designed to reconstitute glutathione in reduced form (anti-oxidant form). The exact mechanism of action of EPI-743 has not yet been determined, but EPI-743 has been shown to be \u00a0potent in vitro protector of cells taken from patients with diseases of the mitochondrial respiratory chain, such as Friedreich’s ataxia, Leigh’s syndrome (SURF1) and Leber’s inherited optic neuropathy.<\/p>\n

Six patients with Leber’s hereditary optic neuropathy are currently being treated with EPI-743 in open-label emergency treatment studies. Improvements in visual acuity, visual field and color vision have been observed.<\/p>\n

Several pediatric patients with Leigh syndrome, Kearns-Sayre syndrome, POLG1 deficiency, MELAS syndrome and Friedreich’s ataxia are currently being treated with EPI-743 in open-label clinical studies. Clinical improvement associated with biomarkers was observed.<\/p>\n

In a recently completed Phase 2A trial, EPI-743 was associated with signs of neurological improvement in 10 included children with Leigh syndrome.<\/p>\n

Our goal is to determine the efficacy and safety of EPI-743 in an open study in 10 patients with X-linked adrenomyeloneuropathy (AMN).<\/p>\n

The main objective of this study is to evaluate the effect of EPI-743 administered orally to subjects with AMN on the change in the association between clinical ALD score in adults ( AACS, Adult ALD Clinical Score) and the dependency rating scale (mRS-9Q) between baseline and the end of 48 weeks of treatment.<\/p>\n

The secondary objectives of this study are evaluated from baseline to up to 48 weeks of treatment. They \u00a0are:<\/p>\n

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  • to assess the safety of EPI-743 for 48 consecutive weeks;<\/li>\n
  • to assess the effect of EPI-743 on motor functions (6 minute walk test distance (6MWT), time required to travel 25 feet (T25FW);<\/li>\n
  • to assess the effect of EPI-743 on disease progression as assessed by the Clinical Overall Impression Improvement Scale (CGIIMP);<\/li>\n
  • to assess the effect of EPI-743 on the change in quality of life (SF-36 questionnaire);<\/li>\n
  • to assess the effect of EPI-743 on the evolution of the auditory evoked potential of the brainstem;<\/li>\n
  • to assess the effect of EPI-743 on changes in hormone levels;<\/li>\n
  • to explore the effect of EPI-743 on altering components of the glutathione cycle.<\/li>\n<\/ul>\n <\/div>\n <\/div>\n<\/section>","protected":false},"excerpt":{"rendered":"","protected":false},"author":2,"featured_media":0,"parent":0,"template":"","news_research_categories":[126],"news_research_tags":[111,114],"class_list":["post-20351","news_research","type-news_research","status-publish","hentry","news_research_categories-clinical-trial","news_research_tags-adrenomyeloneuropathy-amn","news_research_tags-leukodystrophy"],"acf":[],"yoast_head":"\nEPI-743 clinical trial in adrenomyeloneuropathy - ELA International<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/elainternational.eu\/en\/actualites_recherche\/epi-743-clinical-trial-in-adrenomyeloneuropathy\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"EPI-743 clinical trial in adrenomyeloneuropathy - 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