Novel Chelation Therapy Shows Promise for Alzheimer’...

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December 15, 2003

December 15, 2003

An innovative therapy using a drug called clioquinol showed some early promise in slowing the progressive memory loss of Alzheimer's. Men and women with the disease who were given the medicine had less loss of cognitive skills than those who received a lookalike dummy pill, with no serious side effects. The benefits were most noticeable in those in the more severe stages of mental decline.

It is important to stress, however that these results are preliminary. Only a few dozen people participated in the study, which was conducted in Australia. Much more research needs to be done to determine if the drug is truly safe and effective against dementia. A larger trial, co-headed by Dr. Samuel Gandy, Chairman of the Fisher Center for Alzheimer's Research Foundation's Scientific Advisory Board, is being planned for the United States.

In the current Australian trial, researchers from the University of Melbourne tested 36 participants with moderately severe Alzheimer's disease. Half received a twice-daily medicine called clioquinol for 36 weeks. The other half got a lookalike dummy pill. All were given memory tests, as well as blood and physical exams, at regular intervals.

At the end of the study, those patients who had been receiving the medicine had higher scores on memory tests than those who had been getting a placebo drug. They also had lower blood levels of a toxic substance called beta-amyloid.

Most researchers believe beta-amyloid plays an important role in Alzheimer's. The poison is thought to build up in the brains of people affected by the disease and contribute to the formation of sticky deposits called plaques, which choke off and kill healthy brain cells. The result is the progressive loss of memory and other vital thinking skills typical of Alzheimer's.

Metal-Binding Antibiotic

Scientists believe that blocking the production or accumulation of beta-amyloid in the brain may prevent of slow the course of Alzheimer's disease. Numerous drugs and vaccines are being developed in the hopes that they will curb the formation of beta-amyloid and thereby preserve healthy brain function and memory. In tests so far, however, none has yet been proven effective.

The medicine tested in the current trial, clioquinol, is an antibiotic, a type of drug commonly given to fight infections. But clioquinol has another unique property: It binds to certain metals -- specifically zinc and copper -- that circulate in the blood and cellular fluids. These metals are thought to interact with the toxin beta-amyloid and play a role in the formation of brain plaques.

Scientists refer to treatments such as clioquinol that block metals from interacting with other substances in the body as "chelation" (pronounced "key-LAY-shun") therapies. Some alternative practitioners use another form of chelation therapy to treat hardening of the arteries and heart disease, although its benefits have not been proven and some mainstream physicians regard it as quackery.

The type of chelation therapy used in this study is a different technique tailored to the build-up of beta-amyloid that occurs in Alzheimer's disease. The researchers speculate that zinc and copper accumulate in plaque deposits along with beta-amyloid. Removing these metals from the plaque with the drug clioquinol, they propose, causes the deposits to dissolve.

In earlier test tube studies, the drug had been shown to help dissolve the buildup of toxic beta-amyloid and plaque in human brain tissue. When the medication was given to mice that had been bred to develop an ailment resembling Alzheimer's, the animals had much less buildup of beta-amyloid in their brains.

In the current study, the drug did appear to produce some modest benefits in people. "The findings support a proof of concept in humans that drug targeting metal beta-amyloid interactions can have a significant effect on beta-amyloid metabolism, and through this, a beneficial modification on the progression of Alzheimer's disease," the study authors write. "This class of [drugs] may also be considered for related conditions such as Parkinson's disease."

However, as with any emerging therapy, much more work needs to be done. The drug will have to be tested in much larger numbers of people to determine if it is truly safe and effective, a process that can take many years. Still, these early results are at least encouraging and offer a novel approach in the search for a cure.

A trial of clioquinol is being planned for 80 subjects in the United States, providing that safety concerns can be addressed. The American trial is based at the Farber Institute for Neurosciences of Thomas Jefferson University. It is being headed by Dr. Sam Gandy, Institute Director and Chair of the Fisher Center for Alzheimer's Research Foundation Scientific Advisory Board, and Dr. Barry Rovner, Institute Director of Clinical Research.

For more on the treatment of Alzheimer's disease and how researchers at the Fisher Center for Alzheimer's Research Foundation and working towards a cure, visit www.ALZinfo.org.

By www.ALZinfo.org. The Alzheimer’s Information Site. Reviewed by Samuel E. Gandy, M.D., Ph.D., Chairman of the Scientific Advisory Board, Fisher Center for Alzheimer's Research Foundation.

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