New Class of Drugs May Fight Alzheimer's

ByABC News
June 11, 2008, 5:45 PM

June 12 -- WEDNESDAY, June 11 (HealthDay News) -- A class of drugs called gamma-secretase modulators shows potential for treating Alzheimer's disease, a new study suggests.

A hallmark of Alzheimer's is so-called amyloid plaque, which develops tangles in the brain. The gamma-secretase modulators reduce the production of long pieces of amyloid beta protein that stick together and form clumps. At the same time, the drugs increase the production of shorter amyloid beta that blocks longer amyloid beta from sticking together, the researchers explained.

"We have discovered a novel mechanism of action for a class of drugs that are currently being tested as Alzheimer's disease therapeutics," said lead researcher Dr. Todd E. Golde, an associate professor at the Mayo Clinic Department of Neuroscience, in Jacksonville, Fla.

These new drugs don't work in the same way that many other drugs do, Golde said. "Sometimes we think of drugs as magic bullets targeting a single entity, but this drug, by the way it works, could have three consequences that could have a benefit for Alzheimer's disease," he said.

While the new compounds decrease the production of long chains of amyloid beta, Golde said, "Surprisingly, they increase the presence of shorter chains of amyloid beta, which we think actually prevents the accumulation of longer chains of amyloid beta."

"In a short form, amyloid beta is harmless as far as we know," he added. "So you sort of get three bangs for your buck."

"This finding could tell us how drugs for Alzheimer's disease already in clinical trials may be working," Golde said. One of the modulator drugs, tarenflurbil (Flurizan), was in a just-completed phase III clinical trial, and the results should be available this summer, he said.

The latest findings are published in the June 12 edition of Nature.

One expert thinks the new research could produce a drug that could fight the development of amyloid plaque in two ways.

"This is interesting and unexpected," said Dr. Sam Gandy, chairman of the Alzheimer's Association's National Medical and Scientific Advisory Council. "This suggests that it might be possible to design or identify compounds that both modulate generation of amyloid beta and at the same time modulate accumulation of amyloid beta."