Therapeutic Options for Tay-Sachs Disease

Tay-Sachs disease (TSD) is a lysosomal storage disease that is inherited in an autosomal recessive pattern. Lysosomal storage diseases are a group of disorders characterized by deficiency of a specific single lysosomal enzyme, resulting in accumulation of abnormal metabolic products. TSD is characterized by a deficiency in a common lysosomal acid hydrolase, hexosaminidase A (Hex A). An insufficient amount of Hex A causes the accumulation of one of its substrates, GM2 ganglioside. When this accumulation occurs in the neurons of the central nervous system (CNS), the build up GM2 ganglioside leads to diffuse apoptotic cell death. TSD has a variable clinical presentation. It is usually characterized by severe mental retardation and death within two to four years after birth (Chavanay and Jendoubi, 1998). Other symptoms include progressive motor weakness appearing at three to five months of age followed by progressive blindness and decreased attentiveness (Platt and Butters, 1998). Morphologic changes in the neuronal cell population accompany the clinical symptoms. Two well-documented histopathologic findings seen in microscopic studies are ectopic dendritogenesis and axonal spheroid formation (Flax et al., 1998).