The Sena-Esteves laboratory is investigating gene therapy approaches for the treatment of neurodegenerative lysosomal storage diseases such as GM1-gangliosidosis and GM2-gangliosidoses (Tay-Sachs and Sandhoff diseases). We have devised new ways to deliver therapeutic levels of the missing enzymes to the entire brain by injection of adeno-associated virus (AAV) vectors into specific structures in the CNS. Based on the exceptional results that we have obtained in animal models, we are initiating pre-clinical studies that will culminate in a human clinical trial for Tay-Sachs disease. Similar work is planned for GM1-gangliosidosis.
Also we are working on developing new AAV vectors capable of crossing the blood brain barrier for effective gene delivery to the brain after intravascular infusion. We have introduced a new paradigm for brain tumor gene therapy based on the genetic modification of normal brain to create an environment, which is non-permissive to tumor growth. We have demonstrated the effectiveness of this approach for preventing the formation and precluding growth of brain tumors using xenograft models in nude mice. Also we are initiating studies directed at understanding the contribution of different genes to the migratory behavior of GBM cells and strategies to counteract it. Finally we are investigating new gene therapy approaches for Ataxia Telangiectasia.