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Antibodies offer hope for Alzheimer's patients

By Ronald Kotulak
Tribune science reporter
Published July 18, 2006

Treatment with antibodies naturally produced in the body appears to halt the memory-robbing progression of Alzheimer's disease, according to promising early research that scientists plan to expand over the next year.

Scientists from Weill Cornell Medical School in New York reported the findings Tuesday at the 10th International Conference on Alzheimer's Disease and Related Disorders in Madrid. The findings are similar to those from an earlier German study of five patients over six months.

"Those people are not just stabilizing; many of them are getting better. That's quite remarkable," said William Thies, vice president for medical and scientific relations of the Chicago-based Alzheimer's Association.

On the basis of these early results, a larger Phase 2 trial with 24 patients has already begun that will compare the antibody treatment to an inert placebo, and a Phase 3 multicenter trial with 210 patients will start next year.

"We're using something which the human body potentially evolved on its own to deal with this disease," said Cornell's Dr. Norman Relkin, also of the New York Presbyterian Hospital, who presented the trial results in Madrid.

Experts say the need for new drugs is critical because the disease affects an estimated 4.5 million Americans and the number may accelerate as a result of new evidence linking type 2 diabetes with an increased risk of Alzheimer's disease. The cost of the disease in the U.S. is estimated to be $100 billion annually. Diabetes, which is associated with obesity, has reached epidemic proportions in America, affecting an estimated 73 million people.

The patients in the new studies were treated with a product called intravenous immunoglobulin, or IVIg, a concoction of many antibodies collected from blood donated by healthy volunteers. The FDA approved immunoglobulin therapy more than 25 years ago for treating autoimmune diseases.

A single IVIg dose requires the pooled blood of several thousand donors and costs about $3,000. Baxter International Inc. in suburban Deerfield produces IVIg and is funding the clinical trials.

Special immune-system cells circulating in the blood make thousands of different antibodies against germs and other foreign invaders. They also make antibodies to get rid of rogue proteins, which occur as a result of cellular damage or aging.

One of these proteins, beta amyloid, is widely thought to cause the destruction of brain cells that leads to memory loss. Some people are better able to make antibodies against the various forms of beta amyloid, and population studies show they have a lower rate of Alzheimer's disease. People who have low levels of beta amyloid antibodies, meanwhile, are at higher risk for Alzheimer's.

The Cornell researchers believe IVIg works against Alzheimer's because it contains antibodies that neutralize beta amyloid and speed its elimination from the body.

"We have found that there are multiple types of antibodies against the amyloid molecule in IVIg, some targeting the end of the amyloid molecule and some the middle," Relkin said.

Steve Snyder, the National Institute on Aging's program director for the etiology of Alzheimer's disease, said the IVIg research "certainly does look promising from very early pilot data. There is some improvement in cognition in these patients. That goes hand in hand with what we see in the animal studies."

Studies of animals genetically altered to have a form of Alzheimer's disease found that IVIg therapy protected them against the disorder.

IVIg theoretically could be used off-label for patients with Alzheimer's disease before the FDA approves it for that purpose, but Relkin and other researchers said such use would be unwise until the effectiveness of the compound can be scientifically verified.

Although anti-amyloid research has become a high-priority area, drug companies are also pursuing other promising medications, including drugs used to treat type 2 diabetes and inflammation. Population studies suggest that patients taking the diabetes medications Actos or Avandia have a slightly lower risk of developing Alzheimer's disease than patients taking insulin.

The diabetes drugs may work by subduing brain inflammation, which is thought to be caused by beta amyloid and may be the process underlying the destruction caused by Alzheimer's disease.

"The potential link between insulin resistance, inflammation and Alzheimer's disease is very compelling," said Laurie Ryan, assistant program director for the aging institute's clinical trials on Alzheimer's disease. "We do think there's something to this."

When Actos was compared with a placebo in 25 Alzheimer's patients, the drug seemed to slow the disease's progression, researchers from the University of Virginia Health System and Case Western Reserve University reported Sunday in Madrid. But the study was too small to assess the drugs' true clinical benefit, they said.

"There are so many research avenues that people are walking down in this disease that there's bound to be some payoff in one or the other of them in a reasonable period of time—the not too distant future," Snyder said.

Beta amyloid comes in two major forms: the insoluble variety, which creates the telltale brain plaques that are characteristic of Alzheimer's disease, and the soluble form, which new research suggests may be the culprit that kills brain cells.

Relkin and his group theorize that anti-amyloid antibodies in IVIg attach to both varieties of beta amyloid and remove them from the brain.

"What we're doing is giving a big sponge of anti-amyloid antibodies," Relkin said. "So in theory amyloid is being taken away from the compartment that bathes the brain, and, instead, it's driven out toward the periphery where it can be cleared."

rkotulak@tribune.com

Copyright © 2006, Chicago Tribune


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