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By Jennifer Warner
WebMD Medical News
Reviewed By Brunilda Nazario, MD on Monday, December 15, 2003

Dec. 15, 2003 -- A new approach in treating Alzheimer's disease may help improve mental functioning in those with the most severe forms of the disease.

A preliminary study indicates that metal chelation therapy, which targets the proteins involved in creating brain plaques that affect people with Alzheimer's disease, may help slow the progression of the disease. Although the study only involved a small number of patients, researchers say it could open up new directions in Alzheimer's disease treatment.

Metal chelation therapy involves using drugs that block metal ions from interacting with other molecules in the body.

In this study, researchers used the chelation therapy drug clioquinol and found that it lowered levels of the protein beta-amyloid in people with moderately severe forms of Alzheimer's disease (AD).

Researchers say that lowering levels of this protein in the blood may block the production or accumulation of it in the brain and slow Alzheimer's progression. The results appear in the December issue of Archives of Neurology.

Chelation Therapy and Alzheimer's Disease

Researchers say that chelation therapy is thought to work by preventing zinc and copper ions from binding to beta-amyloid, which helps dissolve the protein and prevent it from accumulating in the brain. A buildup of "plaque" in the brain, which includes the protein beta-amyloid -- is thought to cause Alzheimer's disease.

In this phase-two clinical trial, researchers compared the effects of clioquinol with a placebo in 36 people with moderately severe Alzheimer's disease for 36 weeks. Half of the patients received escalating daily doses of the drug twice a day and the others received a placebo.

Tests measured the participants' mental function as well as beta-amyloid levels throughout the study.

By the end of the study, researchers found that plasma beta-amyloid levels declined significantly in the most severely affected patients treated with clioquinol compared with those who received the placebo whose levels continued to increase.

Alzheimer's patients that had taken clioquinol also had better scores on test of mental function.

The study showed chelation therapy was well tolerated in people with Alzheimer's disease. Researchers say those results merit further study of the treatment in larger groups of patients.

The Next Step in Alzheimer's Treatment

In an editorial that accompanies the study, Roger N. Rosenberg, MD, editor of the Archives of Neurology, says that chelation therapy may be a promising new Alzheimer's treatment.

"Clearly, it is an innovative therapeutic approach to AD and merits a closer and more comprehensive assessment in larger clinical trials," says Rosenberg.

Experts say if more studies confirm these results, it may solve an important issue in Alzheimer's disease research.

"If amyloid 'plaque-buster' drugs are effective in preventing or treating Alzheimer's, this may solve the longstanding, often heated controversy surrounding the issue of whether amyloid really causes Alzheimer's or is instead an innocent bystander," says William Thies, PhD, vice president of medical and scientific affairs at the Alzheimer's Association, in a statement released today. "A positive result would lead to a redoubled effort at more and better 'anti-amyloid' medicines; a negative result will send the world's Alzheimer experts back to "square one."

SOURCES: Ritchie, C. Rosenberg, R. Archives of Neurology, December 2003; vol 60: pp 1685-1691, 1678-1679. News release, Alzheimer's Association.

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