Avandia Helps Treat Alzheimer’s Disease

A 500-patient study showed Avandia enhanced memory when compared with a placebo.

For 14 years, neurologist Allen Roses has argued that a gene discovery he made about Alzheimer’s disease would lead to new treatments for the mind-robbing illness. His prediction may finally be coming true.

The study supports a hypothesis that the disease, which affects 4.5 million Americans, is caused by some of the same biological malfunctions that are involved in diabetes. The researchers found that only people with a particular gene linked to a protein that transports cholesterol through the blood responded to the treatment.

“It is one of the first studies to indicate that a drug works for some people and not others based on a test of their genetics,” Roses, 62, said before his presentation at the University of San Diego School of Medicine. The results, he said, suggest “a totally new approach to treating the disease.”

The research involved a longer-lasting version of the drug called Avandia XR that isn’t yet approved in U.S. for treating diabetes. Koenig said Glaxo is planning further tests of Avandia XR and no Alzheimer’s disease trials of the drug are yet scheduled.

The drug works by improving the body’s use of the hormone insulin, which moves glucose from the bloodstream into the body cells. Glaxo’s research indicates Avandia’s impact on Alzheimer’s disease isn’t related to the drug’s effect on insulin. Instead, the drug appears to increase the availability of blood sugar in the brain, which may extend the life of neurons involved in memory, stated Roses.

The U.S. institute says the precise cause of Alzheimer’s is unknown. One idea is that brain cells are killed by clumps of so-called amyloid plaques that are often seen in X-ray images of the brains of deceased victims.

Another notion was first greeted with skepticism by scientists when uncovered in the early 1990s by a genetics lab run by Roses at Duke University in Durham, North Carolina. Roses and his research colleagues found that people who are born with a version of a gene that makes a natural substance called apolipoprotein E, or APOE, are at a high risk of developing Alzheimer’s disease. APOE carries cholesterol through the blood.

Research by other scientists over the years confirmed that people who inherit one type of the gene, called APOE4, are at higher risk than others of developing Alzheimer’s, according to the U.S. institute of aging.

The Gladstone lab published an experiment showing that the No. 4 version of the APOE blood protein interfered with the ability of neurons to make use of glucose in the brain. This inability to access glucose might be killing off crucial brain cells, the Gladstone and Glaxo researchers guessed.

Because, Avandia appears to promote glucose production by neurons, Glaxo undertook a study of 500 patients with mild forms of Alzheimer’s who were being treated in Europe and New Zealand. After six months, Avandia showed no benefit when compared with a placebo. When Glaxo separated patients on the basis of their genetics, it found that those who didn’t have the type 4 variant of the gene showed a “statistically significant” improvement in memory.

Glaxo is seeking U.S. Food and Drug Administration approval for future studies that would include DNA analysis of test subjects. Glaxo said it may undertake larger trials after it gets an agreement from the FDA.

The Pharmacogenomics Journal, Dec 2005