Taking Aim at Tay-Sachs

Taking Aim at Tay-Sachs

Biology Department researchers see hope for managing fatal disease

By Mark Sullivan
Staff Writer

Research being done at Boston College by Prof. Thomas Seyfried (Biology) and his group offers hope for the treatment of Tay-Sachs disease, a fatal genetic disorder commonly found in children of Eastern European Jewish descent.

Prof. Thomas Seyfried (Biology) with research associate Julie Kasperzyk (left) and graduate student Rena Baek. (Photo by Gary Gilbert)
In Tay-Sachs, an enzyme deficiency leads harmful quantities of a fatty substance, or lipid, called ganglioside GM2 to accumulate in the nerve cells of the brain, resulting in a relentless deterioration of mental and physical abilities. Even with the best of care, children with Tay-Sachs disease usually die by age 5. There is no cure.

Now Seyfried is reporting the successful use in mice of a drug that blocks the accumulation of the fatty substances in the brain. "It could represent a real therapy for this disorder," he said.

"The drug - NB-DGJ for short - is a small, artificial imino sugar molecule that blocks the first step in the synthesis of the types of lipids that accumulate in the brain in Tay-Sachs," said Seyfried.
"If you don't synthesize these lipids, they can't accumulate, and the patient should be saved from the devastating effects of their accumulation."

In the Jewish population, the disease's frequency is potentially as high as one in 2,500, and one in 30 is a carrier of the Tay-Sachs gene. The disorder also is noted with heightened frequency among French Acadians or Cajuns.

A four-year grant of $840,000 from the National Institutes of Health is supporting Seyfried's research.

This past July, Seyfried received $33,000 from the National Tay-Sachs and Allied Diseases Association, one of the first research grants made by the Brighton-based group, which traditionally has focused its resources on family assistance.

"Dr. Seyfried's work represents a critical dimension in potential therapeutic approaches," said Jayne Gershkowitz, executive director of NTSAD, one of the country's oldest genetic disease organizations.

"While other scientists study gene therapy, neural stem cells, bone marrow transplantion and metabolic bypass therapies, the research community agrees that no one technique will be the solution. It is likely that a combination of therapies, mixed together in just the right "recipe," will be needed to halt or even reverse the ravaging effects of Tay-Sachs, Sandhoff and similar diseases. We are hopeful that Dr. Seyfried's efforts will yield a key ingredient for this recipe."

Seyfried's group includes research associate Julie Kasperzyk, graduate students Eric Hauser and Rena Baek, and undergraduate research assistants Christine Denny and Matthew LaLone.

The BC researchers have worked in collaboration with an Oxford colleague, Frances Platt, who Seyfried said developed the strategy for blocking the lipids' synthesis and accumulation.

"We proved the principle, that if you block the synthesis, you block the storage," he said.

The Seyfried group presented a preliminary report on its findings at the Society for Glycobiology conference in Boston this past November.
"The reason we're excited is this offers, for the first time, hope," said Seyfried. "There's no cure for Tay-Sachs, and there have been no therapies. Nothing has ever worked.

"This is a therapy. We're not curing the disease or eliminating the cause. But the disease might be managed. We may prevent some of the consequences.

"We need many more years of basic research. But if it works out the way we think it will, it will represent the first real opportunity for a therapeutic approach to the disease.

"This is not a cure. But it's a therapy. In the past, they had no therapies."

More information on Seyfried and his research is available on the World Wide Web at /schools/cas/biology/facadmin/seyfried/.


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