8.01.2004

Scientists May Have Found New Way to Treat Alzheimer's in Study

Pfizer Inc. and Cleveland Clinic researchers may have uncovered a new route to keep the body from making a substance that clogs the brain in Alzheimer's disease, according to a study in the Aug. 1 Nature Medicine.

Scientists and drug companies have been searching for a way to disable or hamper the body's production of BACE1, an enzyme responsible for the production of beta amyloid, since it was discovered in 1999. Beta amyloid is the main component of the plaque that collects between the nerve cells in the brains of people with Alzheimer's, a central feature of the disease.

Now researchers have found a natural protein in the body that binds to BACE1, probably decreasing amyloid production and perhaps slowing the dementia associated with Alzheimer's. In laboratory tests, increased quantities of the Nogo family of proteins substantially reduced production of beta amyloid, said Riqiang Yan, senior author of the paper.

"We identified a potential therapeutic target that may inhibit the production of amyloid and slow down the progression of Alzheimer's disease," Yan, an associate staff member of the Cleveland Clinic Foundation, said in a telephone interview.

About 4.5 million Americans suffer from Alzheimer's, which claimed the life of former U.S. President Ronald Reagan last month after a decade-long battle with the disease.

One member of the Nogo protein family is responsible for regulating nerve growth, particularly after an injury. Additional studies are under way to confirm that the proteins can inhibit amyloid production in animal models, Yan said.

Yan, a discoverer of the BACE1 enzyme, was working at Pfizer's Pharmacia unit when the study began. Scientists at both locations are now studying the proteins independently. It's still not known how to manipulate the protein levels in the human brain, Yan said.

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