High Levels of Frataxin Overexpression Lead to Mitochondrial and Cardiac Toxicity in Mouse Models.

ABSTRACT: Friedreich ataxia (FA) is currently an incurable inherited mitochondrial disease caused by reduced levels of frataxin (FXN). Cardiac dysfunction is the main cause of premature death in FA. Adeno-associated virus (AAV)-mediated gene therapy constitutes a promising approach for FA, as demonstrated in cardiac and neurological mouse models. While the minimal therapeutic level of FXN protein to be restored and biodistribution have recently been defined for the heart, it is unclear if FXN overexpression could be harmful. Indeed, depending on the vector delivery route and dose administered, the resulting FXN protein level could reach very high levels in the heart, cerebellum, or off-target organs such as the liver. The present study demonstrates safety of FXN cardiac overexpression up to 9-fold t

SUBMITTER: Belbellaa B 

PROVIDER: S-EPMC7648087 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature