Biology and potential strategies for the treatment of GM2 gangliosidoses

Abstract The G M2 gangliosidoses are a group of heritable neurodegenerative disorders caused by excessive accumulation of the ganglioside G M2 owing to deficiency in β-hexosaminidase activity. Tay–Sachs and Sandhoff diseases have similar clinical phenotypes resulting from a deficiency in human hexosaminidase α and β subunits, respectively. The lack of treatment for G M2 gangliosidoses stimulated interest in developing animal models to understand the molecular mechanisms underlying the various forms of this disease and to test new potential therapies. In this review, we discuss the molecular biology of G M2 gangliosidoses and the different strategies that have been tested in animal models for the treatment of this genetic disorder, including gene transfer and cell engraftment of neural stem cells engineered to express the hexosaminidase isoenzymes.