THÈME DE RECHERCHE : 

Développement d’une approche par thérapie génique pour traiter les dystrophies rétiniennes dues à des mutations dans CRX.

Development of a gene therapy approach to treat CRX-associated inherited retinal dystrophies.

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SUBVENTION JED : 22.500 €

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OBJECTIF DU PROJET : 

Inherited retinal dystrophies (IRDs), characterized by progressive loss of photoreceptors (PR), are a common cause of visual impairment. IRDs are a group of genetically and clinically heterogeneous diseases with more than 250 causative genes, which makes therapeutic development challenging1. Encouragingly, the efficacy and safety of adeno-associated virus (AAV) vector-mediated gene therapy for some recessive IRDs has been proven clinically2,3. Our experience with dominant mutations in genes encoding PR transcription factors has highlighted their high potential to be also good targets for future gene therapy development. As such, the cone-rod homeobox transcription factor, CRX, is an ideal candidate4. In this context, our general objective is to develop a CRX gene replacement strategy to treat dominant CRX-dependent IRDs using mouse models carrying different CRX mutations. Our research hypothesis is that a CRX-expressing AAV vector could override the negative effects of CRX dominant mutations. The preclinical value of our project resides in the investigation of novel and innovative therapeutic strategies to potentially treat patients with CRX-associated retinopathies, especially children with Leber congenital amaurosis (LCA).