Improved efficacy of FKRP AAV gene therapy by combination with ribitol treatment for LGMD2I.

ABSTRACT: Mutations in the fukutin-related protein (FKRP) gene cause dystroglycanopathy, with disease severity ranging from mild LGMD2I to severe congenital muscular dystrophy. Recently, considerable progress has been made in developing experimental therapies, with adeno-associated virus (AAV) gene therapy and ribitol treatment demonstrating significant therapeutic effect. However, each treatment has its strengths and weaknesses. AAV gene therapy can achieve normal levels of transgene expression, but it requires high doses, with toxicity concerns and variable distribution. Ribitol relies on residual FKRP function and restores limited levels of matriglycan. We hypothesized that these two treatments can work synergistically to offer an optimized therapy with efficacy and safety unmatched by each treat

SUBMITTER: Cataldi MP 

PROVIDER: S-EPMC10727973 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature