AAV-mediated gene therapy of spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) and Farber disease - Archive ouverte HAL Accéder directement au contenu
Poster De Conférence Année : 2022

AAV-mediated gene therapy of spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) and Farber disease

Résumé

Farber disease (FD) and spinal muscular atrophy with progressive myoclonic epilepsy (SMAPME) are autosomal recessive disorders caused by mutations in the ASAH1 gene, which codes for acid ceramidase (ACDase), a lysosomal enzyme that catalyses the bioactive lipid ceramide into sphingosine and fatty acid. These ASAH1-related disorders present with a spectrum of clinical manifestations and lead to death in most cases during early infancy (FD) or at teenage (SMA-PME). To date, there is no curative treatment for patients and therefore a clear unmet medical need. In the present study, we evaluated a gene therapy approach in a mouse model of acid ceramidase deficiency. We report that intravenous administration of a recombinant AAV9 vector expressing human ACDase in diseased Asah1P361R/P361R mice prolonged survival of all animals until the end of a 6-month study, restored body growth and motor activity, and abolished inflammation in peripheral tissues and the central nervous system. Our findings provide proof-of-concept that systemic AAV-mediated ASAH1 gene replacement can rescue the severe phenotype of a mouse model of acid ceramidase deficiency, paving the way for clinical translation in patients.
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Dates et versions

hal-04453821 , version 1 (12-02-2024)

Identifiants

  • HAL Id : hal-04453821 , version 1

Citer

Jérôme Denard, Martina Marinello, Virginie Latournerie, Delphine Bonnin, Karine Poulard, et al.. AAV-mediated gene therapy of spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) and Farber disease. ASGCT 2022, May 2022, Washinghton DC, United States. ⟨hal-04453821⟩
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