Novel Therapies Fight Alzheimer's on Multiple Fronts

Insulin, immune system and even calisthenics offer hope, experts say

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HealthDay Reporter

MONDAY, June 20, 2005 (HealthDay News) -- Future treatments for Alzheimer's disease may run the gamut from calisthenics combined with singing, Chinese herbs, immune-boosting therapies and insulin delivered to the brain via the nose.

Research in these areas and more was presented Monday at the Alzheimer's Association International Conference on Prevention of Dementia, held in Washington, D.C.

Several of the proposed treatment methods target beta-amyloid, the abnormal brain protein that is thought to be the culprit behind Alzheimer's disease.

"The amyloid theory is really solidifying over time. I'm a firm believer," said Dr. John Stoukides, medical director of the Rhode Island Mood and Memory Research Institute.

The first study, a phase II trial, found that patients with mild Alzheimer's disease taking a drug called Flurizan were able to slow the disease-related decline in their activities of daily living (such as eating and dressing) by about 67 percent when compared with people on placebo.

"This is the most important thing for people with Alzheimer's," said Stoukides, who is an investigator for the continuing trials of the drug.

"We want to identify [Alzheimer's patients] early, treat it quickly and aggressively, and stop them from getting worse than they are at a good point. It's the [decline in] activities of daily living you really want to slow down because that's what puts people in nursing homes," Stoukides said.

Flurizan is the first of a new class of drugs known as selective amyloid beta- lowering agents, which are intended to affect the suspected underlying cause of the disease, a buildup of beta-amyloid protein. All of the FDA-approved treatments now available only provide relief of cognitive symptoms; they do not attack underlying disease.

In a second trial, this one involving eight people with mild to moderate Alzheimer's, researchers at Weill Medical College of Cornell University tried to harness the body's immune system to fight Alzheimer's.

In this trial, intravenous immunoglobulin (IVIg) seemed to increase the levels of anti-beta-amyloid antibodies in the blood to a greater degree than seen before (an average 45 percent decrease). Six of the eight patients experienced improvement in cognitive function; none of the patients had declining function.

Previous studies had noted that levels of these antibodies seemed to be lower in people with Alzheimer's. IVIg is derived from human blood and contains high concentrations of antibodies.

"Some people naturally have antibodies to amyloid," explained William Thies, vice president of medical and scientific affairs for the Alzheimer's Association, at a teleconference last Tuesday. "This has the potential to give us a product with a known safety profile to test the amyloid hypothesis. It becomes a very important scientific tool."

It's not entirely clear how the process is working but "the antibodies mobilize amyloid beta from the cerebrospinal fluid into the bloodstream," explained study author Dr. Marc Weksler, the Wright Professor of Medicine at Weill Medical College of Cornell University in New York City.

According to Weksler, amyloid clearance might be due to a flushing effect (i.e., antibodies in the brain are working to flush out the protein) or a magnet-like effect (the antibodies are drawing or attracting the protein into the bloodstream).

A third study found that insulin delivered intranasally benefited individuals with both early Alzheimer's and abnormal insulin regulation. Previous research has indicated that people with high levels of insulin in their blood may be at an increased risk of developing Alzheimer's. This is because insulin congregates in the blood vessels and fails to reach the brain, where it is needed for various regulatory processes.

Another way to get insulin to the brain is through the nose, however. And in this study, conducted at the University of Washington School of Medicine and Veterans Affairs Puget Sound Medical Center, insulin delivered intranasally did improve memory recall for Alzheimer's patients. The participants were able to remember a list of words after taking a higher insulin dose, the researchers report.

A fourth study, this one conducted in China, found that an herbal extract improved cognitive function in people with mild cognitive impairment, often a precursor to Alzheimer's. The extract, known as GETO (for ginseng, epimedium herb, thinleaf milkwort root and two other herbs), has been used for centuries in traditional Chinese medicine.

Finally, a study out of Japan's University of Tsukuba found that an exercise program incorporating low-intensity calisthenics also improved memory in elderly people with mild cognitive impairment.

The calisthenics, called Furfuri-Guppa, were combined with singing. After one year, 70 of participants in the exercise intervention showed a significant improvement in memory.

"We have a multitude of mechanisms represented," Thies said. "I think it is fair to say, at this point, that we don't know exactly which mechanism or which intervention is going to be the most successful in becoming an actual therapeutic product. But the more mechanisms you have, the more likely you are to have some success."

More information

The Alzheimer's Association has more on current treatments for Alzheimer's.

SOURCES: John Stoukides, M.D., medical director, Rhode Island Mood and Memory Research Institute, East Providence, R.I.; Marc Weksler, M.D., Wright Professor of Medicine, Weill Medical College of Cornell University, New York City; William H. Thies, Ph.D., vice president of medical and scientific affairs, Alzheimer's Association, Chicago; June 20, 2005, scientific presentations, Alzheimer's Association International Conference on Prevention of Dementia, Washington, D.C.

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