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, we aim to develop gene-editing approaches to downregulate the expression of the mutated GFAP protein or correct mutations in the Gfap gene in an animal AxD model. 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, we expect to outline novel editing platforms that could be applied prospectively for disease modeling studies and treatments of other leukodystrophies characterized by astrocyte degeneration or dysfunctional/maladaptive astrogliosis

Project financed by ELA up to: 100 000 €