The mission of TIGEM’s Molecular Therapy (MT) research plan is to develop novel strategies for the prevention and treatment of disease. One of our major research strategies is in vivo vector-mediated gene delivery. The general objective is to develop new vector systems using adeno-associated vectors (AAV) and helper dependent adenoviral vector (HDad) delivery methods, test them in the appropriate animal models, uncover the mechanisms involved in vector transduction, and then finally move the most promising approaches to the clinic.
Here at TIGEM, the AAV vector system has been particularly successful when used in several pre-clinical studies on lysosomal storage disorders (LSDs) and in vast series of animal models of retinal degenerations including albinism, retinitis pigmentosa, Stargardt disease, and Leber congenital amaurosis. We have also successfully used this vector system in the clinic to treat the retinal degenerative disease LCA2 RPE65. This was one of the first gene therapy trials for the treatment of an inherited ocular disease, and it showed very encouraging results, supporting the validity of subretinal administration of AAV in humans.
Finally, we also utilize small molecules such as particular chaperones for the treatment of LSDs. TIGEM's long-standing experience in studying metabolic diseases has generated clear evidence that small chaperones can increase enzymatic activity of alpha-glucosidase, the protein product of a mutated gene in Pompe disease. These results have direct implications for the treatment of the disease and for the efficacy of enzyme replacement therapy (ERT). Such data have led to the first clinical trial testing the efficacy of the combined use of chaperones and ERT in patients with Pompe disease.