Tay-Sachs disease is a progressive neurological lysosomal storage disorder resulting from deficiencies in the ability of HexA to catabolize GM2 ganglioside. The excessive neuronal accumulation of GM2 ganglioside is accompanied by progressive neurological deterioration affecting motor, cerebral and spinocerebellar functions. These diseases are rare genetic conditions (<1000 people in the US and Canada) for which there is no effective treatment.

Tay-Sachs is categorized by onset and severity into three clinical-subtypes: Classic Infantile, Juvenile and Late-Onset (also called Adult-Onset). Onset and disease progression is a reflection of lysosomal HexA concentrations and activity. Classic Infantile Tay-Sachs is caused by a null mutation in hexA, the gene that encodes one of the two evolutionarily related HexA subunits. The complete absence of HexA in Classic Infantile Tay-Sachs is associated with the most severe form of the disease. Disease progression is characterized by a rapid and relentless deterioration of mental and physical abilities until death typically by age 3 or 4. Late-Onset Tay-Sachs (LOTS) is caused by a reduction as opposed to complete loss in HexA activity. Pharmacological chaperones may represent a relevant form of therapy provided that some amount of HexA is minimally present as it is with Juvenile Tay-Sachs and LOTS. Initial symptoms of Juvenile and LOTS may include clumsiness, mood alterations, and muscle weakness. As affected individuals age, they may exhibit tremors, muscle twitching, slurred speech, and an inability to coordinate voluntary movements. Approximately 40% of LOTS patients experience significant depression or bipolar disorder. It is believed that progress with a safe and effective treatment for LOTS will facilitate the development of a therapeutic for Juvenile Tay-Sachs.