BRAINCAV · NONHUMAN ADENOVIRUS VECTORS FOR GENE TRANSFER TO THE BRAIN

Formidable challenges remain to prevent and treat successfully neurodegenerative diseases. Traditional pharmacological approaches, as well as those using stem cells, have made progress but their impact remain limited. As suggested by clinical results in Canavan and Parkinson’s disease, gene transfer offers substantial potential. However, this strategy of therapeutic intervention also brings unique obstacles - in particular the need to address feasibility, efficacy and safety. BrainCAV's foundation is the potential of canine adenovirus type 2 (CAV-2) vectors, which preferentially transduce neurons and undergo a very efficient long-distance targeting via axonal transport. Moreover, the episomal long-term expression leads to safe, efficient neuron-specific gene delivery. We proposed a structured translational approach that spans basic research through pre-clinical model feasibility, efficacy and safety. To provide a proof-of-principle of the effectiveness of CAV-2, we tackle mucopolysaccharidosis type VII, a global, orphan disease commonly affecting children, and Parkinson's disease, a focal degeneration of dopaminergic neurones commonly affecting aged population. To develop and execute this project, BrainCAV brings together an interdisciplinary combination of partners with unique expertise that will take CAV-2 vectors to the doorstep of clinical trials.