Tay-Sachs disease is a fatal neurodegenerative disease which usually kills children before age six. It occurs most commonly among Ashkenazi Jews and French-Canadians in Eastern Quebec.
There is no known cure for Tay-Sachs disease, which is caused by a deficiency of an enzyme called beta-hexosaminidase A. The condition occurs when the fetus inherits two chromosomes, one from each parent carrying the Tay-Sachs gene. Onset of the disease usually begins by age one, leading to muscle impairment, seizures and finally death.
One of the world's leading researchers into the rare genetic disorder is Dr. Barbara Triggs-Raine in the department of biochemistry. A U of M graduate, she began studying Tay-Sachs eight years ago during postdoctoral training. She has since received subst antial funding for her research projects, recently including a three-year grant from the Medical Research Council of Canada. She is a full associate investigator in the Canadian Genetic Diseases Network of Centres of Excellence.
Triggs-Raine's research focusses on the biochemical and molecular basis of lysosomal enzyme deficiencies. Her work includes the study of benign mutations that cause an apparent enzyme deficiency but do not actually cause Tay-Sachs disease.
Triggs-Raine identified the first two benign mutations, the second in her own laboratory. Couples who are predicted through enzyme screening to carry the Tay-Sachs gene might in the past have been advised to avoid having children. The work done by Trig gs-Raine now helps better predict whether the unborn child is likely to be normal. Recently, her laboratory identified several potential benign mutations in the French-Canadian population.
DNA testing for these mutations is now a recommendation of the World-Wide Tay-Sachs Disease Prevention Program.
There have been at least two cases where DNA testing showed couples had a benign mutation but still had normal children, even though they appeared to be likely candidates to have children with the disease.
"This work won't lead to a cure for Tay-Sachs, but it helps us greatly in predicting which couples might have a child with Tay-Sachs," Triggs-Raine notes. "It allows doctors to provide much more accurate counselling."
Her work may eventually be of direct benefit to diabetes sufferers as well. In 1993, she began a study of diabetes in collaboration with Dr. Dan Gietz of the department of human genetics. Diabetes affects three per cent of the western population and up to 8.7 per cent of the North American native population.
Supported by the Canadian Genetic Diseases Network, a $65,000 grant from the Manitoba Health Research Council and matching funds from industrial partner Merck Frosst, the aim of their research is to study protein intereactions within cells and to identif y novel and existing proteins that may be a target for new antidiabetic drugs. Says Triggs-Raine: "We are trying to understand why insulin isn't available or doesn't function properly in certain forms of diabetes."
She adds: "The end result isn't a cure, but an attempt to identify proteins which can be targeted by therapeutic drugs."