In the 1990s laboratories in the United States, Canada, and France developed mouse models of Tay-Sachs disease, Sandhoff disease and GM2 activator deficiency. These investigations led to a much better understanding of the brain pathology and progression of the diseases. A significant outcome has been the use of the mouse models to experiment with approaches to therapy. A promising approach is based on partially blocking the synthesis of gangliosides with drugs so that accumulation of GM2 ganglioside becomes minimal. In addition to "substrate deprivation," as this blocking action is called, other laboratories are trying gene therapy and drug-based methods for bypassing the Tay-Sachs defect. The combination of carrier testing and prenatal diagnosis to assure the birth of healthy babies, and the more recent prospects for treating affected patients are major advances since the discovery of a cherry-red spot described in the first infant known to have been born with Tay-Sachs disease.
SEE ALSO CELL, EUKARYOTIC; DISEASE, GENETICS OF FOUNDER EFFECT; GENE; GENETICS OF DISEASE; HETEROZYGOTE ADVANTAGE; METABOLIC DISEASE; MUTATION; POPULATION SCREENING; PRENATAL DIAGNOSIS; PROTEINS; RNA PROCESSING; RODENT MODELS.
Roy A. Gravel
Gravel, Roy A., et al. "The GM2 Gangliosidoses." In The Metabolic and Molecular Bases of Inherited Diseases, 8th ed., Charles R. Scriver, Arthur L. Beaudet, William S. Sly and David Valle, eds. New York: McGraw-Hill, 2001.
"HEXA Locus Database." <http://data.mch.mcgill.ca/gm2-gangliosidoses>.
"Tay-Sachs Disease." National Center for Biotechnology Information, Division of Online Mendelian Inheritance in Man. <http://www.ncbi.nlm.nih.gov:80/entrez/dispomim.cgi?id=272800>.