Warning: Hepatotoxicity of gene therapy in a female mouse model of Rett syndrome.

The Human Neurogenetics team shows that the treatment of mouse models of Rett syndrome, with an AAV9-Mecp2 viral vector, allows phenotypic improvement limited to respiratory problems only. The use of a higher dose causes sometimes fatal side effects, linked to the massive presence of the virus in the liver. Post-mortem hepatic analyses reveals the presence of apoptosis correlated with an increase in the level of CHOP protein, a marker of UPR response whose activation induces cell death.

These results, published in Neurobiology of Diseases, stress the need for additional preclinical work to limit the side effects of gene therapy in Rett syndrome.