Alzheimer's Vaccine Gets Second Wind

New Clues Point to Safer Vaccine, Effective Treatment

From the WebMD Archives

Oct. 14, 2002 -- When it made mice with Alzheimer's disease regain mental function, it looked like a cure. When it made people's brains swell dangerously, it looked like a disaster. Between these two extremes, a promising vaccine now points the way to new Alzheimer's treatments.

The idea behind the vaccine -- Elan Corp.'s AN1792 -- is simple. It harnesses the power of the immune system to attack the plaques that clog the Alzheimer's patients' brains.

To do this, the vaccine uses a synthetic version of the plaque's main ingredient, beta amyloid (Aß). This 42-piece synthetic molecule, dubbed Aß42, causes the immune system to make Aß-blocking antibodies. Special mice bred to develop Alzheimer's disease do a lot better when vaccinated with Aß42.

Unfortunately, human trials found that about 6% of Alzheimer's patients injected with Aß42 developed a dangerous brain swelling. The cause of this inflammation wasn't clear. Now further study of these patients shows that vaccinated patients developed powerful anti-Aß antibodies. Whatever it was that caused the brain inflammation, these antibodies don't seem to be the culprit. The antibodies avidly attacked plaque -- but not human brain cells.

That's very good news, says study leader Roger M. Nitsch, MD, director of psychiatry research at the University of Zurich, Switzerland. Nitsch and colleagues report their findings in the Oct. 15 online issue of Nature Medicine.

"The high degree of specificity of the antibodies is a remarkable finding. It argues in favor of the vaccination strategy," Nitsch tells WebMD. "We were pleased by the absence of unwanted cross-reactions with normal brain cells."

Of course, it's one thing to attack plaque, and another thing to stop the awful march of Alzheimer's disease. Nitsch and colleagues are carefully watching people who got the vaccine in European and U.S. studies. By next summer they should know whether the patients are doing better.

"Clearly, further research is required to improve the safety of this novel therapeutic strategy," Nitsch says. "Our patients are now carefully followed up to determine whether the vaccination is effective in preventing cognitive decline and progression of dementia."


Big help comes from another research group led by JoAnne McLaurin, PhD, at Canada's University of Toronto. This team was the first to show that the Elan vaccine could improve Alzheimer's symptoms in mice. Now they have the found the key to why the vaccine works, why it causes brain inflammation, and -- most important -- how it might be improved.

In the same issue of Nature Medicine, the McLaurin team reports that a small piece of Aß42 -- Aß4-10 -- raises the same plaque-stopping antibodies as the larger molecule. And in mouse studies, it doesn't cause brain inflammation. Some part of the larger molecule apparently triggers immune responses linked to inflammation.

McLaurin says it looks like the small segment of amyloid protein attacked by anti-Aß4-10 antibodies may be the main troublemaker in Alzheimer's disease. This target appears to be essential for amyloid to self-assemble into plaque.

"The theory -- and I stress that this is only a theory -- is that the anti-Aß4-10 antibody targets an amyloid assembly product, and by pricking out this one product you stop neuronal loss," McLaurin tells WebMD.

It may be that using Aß4-10 as a vaccine would be safer and as effective as the previous version of the Elan vaccine. On the other hand, Nitsch says, it might be better to treat patients with antibody itself -- a strategy known as passive immunization. Or it might be possible to give the vaccine along with drugs to prevent brain inflammation.

McLaurin's team is working on another approach. They're looking for a small molecule that mimics anti-Aß4-10 antibodies. The hope is that such a drug would be small enough to penetrate the brain and stop Alzheimer's disease cold in its tracks. And since people vary enormously in their response to vaccines, an anti-Aß4-10-like drug likely would work for more patients.

What kind of hope does this offer for people who have Alzheimer's disease today? McLaurin warns that research is still in its early stages, but she holds out hope that this approach might work.

"Someone who has florid Alzheimer's disease right now is probably too far along," she says. "But someone in the early stages of the disease has potential to be in clinical trials that will come along. Potentially it will halt the disease -- but it won't bring back anything that they have lost."-->

WebMD Health News
© 2002 WebMD, Inc. All rights reserved.