Alexander disease (AxD) is a rare autosomal dominant disorder caused by point mutations in the gene encoding for the glial fibrillary acidic protein (GFAP), the major intermediate filament protein in astrocytes. Accumulation of GFAP protein in Rosenthal fibers leads to astrocytic dysfunctions and altered development and homeostasis of affected brain tissues.

No cures are currently available for AxD patients. In the proposed pilot project, the team aim to develop a gene editing approach to specifically downregulate the expression of the mutated GFAP protein in affected AxD astrocytes. This project will collect solid proof-of-concept data for the future progress of a novel and definitive gene therapy strategy for the treatment of AxD patients. In addition, they expect to outline novel editing platforms that could be applied prospectively for disease modelling studies and therapeutic treatments of other leukodystrophies characterized by astrocyte degeneration or dysfunctional/maladaptive astrogliosis.

Project financed by ELA up to: 60 000 €