Canavan disease is a devastating degenerative disorder of the white matter caused by mutations in the aspartoacylase (ASPA) gene. Dr. Gao and his lab has a long history in Canavan disease research. In his PhD thesis work, Dr. Gao cloned, characterized the ASPA gene and genetic mutations associated with Canavan disease while at Dr. Matalon’s lab. This work laid the foundation for future therapeutic research, including gene therapy. Dr. Gao’s PhD mentor’s lab was also the first to develop a Canavan disease mouse model that, again, was a milestone in Canavan disease research.
Dr. Gao’s lab started Canavan disease gene therapy in 2008
Later, during his post-doc and junior faculty years at Dr. Wilson’s Institute for Human Gene Therapy at UPenn, Dr. Gao discovered a plethora of second generation adeno-associated viruses (AAV) serotypes that are capable of crossing the blood-brain barrier (BBB) when given intravenously and thus revolutionized brain directed gene therapy and enabled scientists around the world to developed new strategies to treat genetic disorders of the brain; nowadays, AAVs are widely used in many clinical trials.
With these groundbreaking scientific contributions in mind, Dr. Gao’s lab started Canavan disease gene therapy in 2008 when he joined UMass as the founding director of the Gene Therapy Center and Vector Core.
Since then, Dr. Gao’s lab has extensively been developing AAV based gene therapy and pathomechanistic research for Canavan disease. The current 3rd generation gene therapy developed by a research team led by Dominic Gessler, a physician scientist fellow in Gao lab can completely normalize the CD knock-out mouse that dies around 28 days of age when untreated. Curiously, this 3rd generation gene therapy turns treated mice into “supermice”, outperforming healthy wild-type mice on motor function testing. In a second mouse model with a milder phenotype and almost normal survival but severe neurologic symptoms, the 3rd generation gene therapy is able to rescue even mice treated at much later adult age. Most importantly, many unpublished data suggest that the gene therapy becomes effective within weeks after treatment in mouse.
So far, Gao lab has successfully treated hundreds of mice at different ages that demonstrate the efficacy of this gene therapy. Now, Dr. Gao’s lab working towards the clinical translation of this potent 3rd generation gene therapy that only requires a single intravenous injection to treat Canavan disease in mice.