New roles for old medications

The elusive search for an effective drug for Alzheimer’s patients has scientists testing medicines already in use to treat diabetes, high cholesterol and rheumatoid arthritis, with varying degrees of success.

Current drug research is focused on potential treatments for the underlying causes of Alzheimer’s, with diabetes and high cholesterol both recognized as risk factors for the brain-killing disorder.

Neil Buckholtz, chief of the Dementias of Aging Branch of the National Institute on Aging, said findings from some small studies suggest that a drug approved for control of blood sugar in diabetes (Avandia), as well as statin drugs known to lower cholesterol “show promise” as potential treatments for Alzheimer’s patients.

Three large trials with those drugs are under way, Mr. Buckholtz said in an interview, and he anticipates results from each next year.

But much of current research in the United States is aimed at curtailing the volume of amyloid-beta — a sticky protein that accumulates excessively in the brains of Alzheimer’s patients. A buildup of amyloid-beta results in its clumping together and forming “plaque,” which harms brain tissue.

Mr. Buckholtz said the thrust of this research is to inhibit enzymes that make amyloid. This is being done, he said, “by decreasing its production or increasing its clearance” from the brain.

Dr. John C. Morris, director of the Alzheimer’s Disease Research Center at Washington University at St. Louis, is involved in two different vaccine studies in which antibodies for amyloid are being grown in the laboratory for infusion into Alzheimer’s patients.

“Both studies are promising,” he said in a telephone interview.

An Alzheimer’s patient living in Potomac says he would like to see local trials of an arthritis drug called Enbrel. The man was encouraged by a recent article in the Los Angeles Times that said the memories of Alzheimer’s patients immediately improved after they were injected with Enbrel in a small “preliminary” study conducted at UCLA between September 2004 and last April. The drug was injected into the back of the neck, above the spine.

However, Mr. Buckholtz said it is far too early to be excited about Enbrel as an Alzheimer’s therapy.

In patients with the autoimmune disorder rheumatoid arthritis, Enbrel disables an inflammation-inducing molecule known as tumor necrosis factor-alpha (TNF) that causes joint pain.

“There is inflammation in the brains of Alzheimer’s patients,” explained Mr. Buckholtz, and studies have shown high levels of TNF in the spinal fluid of Alzheimer’s patients. “A number of anti-inflammatory drugs have been tested [as Alzheimer’s medications] without a great deal of success.”

As for the Enbrel trial led by Dr. Edward Tobinick, assistant clinical professor of medicine at UCLA, Mr. Buckholtz noted that it was “not controlled” with a placebo and involved only 15 patients.

“There have been a number of small trials in which the drugs that were tested seemed very interesting, but when the same drugs were tested in larger trials, they did not pan out,” Mr. Buckholtz said.