CAV-4-MPS

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. The foundation of this project 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, for treating the neurological symptoms of mucopolysaccharidoses (MPS). We proposed a structured translational approach that spans basic research through pre-clinical model feasibility, efficacy and safety. To provide a proof-of-principle we tackle mucopolysaccharidosis type VII as a model of MPS. The episomal long-term expression of helper-dependent CAV-2 vectors leads to stable, safe and efficient neuron-specific gene delivery for a genetic rare disease that needs low but sustained expression of the missing enzyme for the life of the patient. To develop and execute this project, we propose the coordination of an interdisciplinary combination of partners with unique expertise that will bring a novel viral vector from bench to bedside and allow a better understanding and treatment of neurodegeneration caused by MPS.