Side Effects Force Halt To Alzheimer’s Vaccine Trial

Of the 1,000 or so research presentations at the World Alzheimer Congress 2000, nothing caused as much hoopla as the announcement by Dale Shenk, Ph.D., of Elan Pharmaceuticals in San Francisco that a vaccine against beta amyloid—the stuff from which Alzheimer’s plaques are made—appeared to be a very promising treatment for Alzheimer’s disease (Psychiatric News, August 18, 2000).

Now, two years later, another international Alzheimer’s conference has taken place, in July in Stockholm. But nothing was reported at this conference about Elan’s beta amyloid vaccine research. The reason, it appears, is that Elan had to stop testing the vaccine on Alzheimer’s subjects because of central nervous system inflammation in some of the subjects.

Psychiatric News obtained this information from interviews with two Alzheimer’s scientists who attended the Stockholm conference—Blas Frangione, M.D., Ph.D., a professor of psychiatry and pathology at New York University School of Medicine, and Agneta Nordberg, M.D., Ph.D., a professor of clinical neuroscience at the Karolinska Institute in Stockholm. Psychiatric News also attempted to confirm this information with Elan, but neither Shenk nor an Elan spokesperson in New York City returned calls. However, the information was also reported by BBC News and The Scientist earlier this year.

“Of course the vaccine was fascinating,” Nordberg told Psychiatric News, “and I think the idea of vaccination is something that is accepted. But this was an example, I think, of perhaps moving too quickly from animal studies to trials on humans.”

Nonetheless, Frangione told Psychiatric News, a number of Alzheimer’s scientists, including himself, are still hopeful that a beta amyloid vaccine might pan out as a safe and effective treatment for Alzheimer’s disease and are pursuing research in that direction.

For example, he and his colleagues have developed beta amyloid peptides that are similar, but not identical, to the beta amyloid used in Elan’s human experiments. They have used the peptides to immunize mice that had been engineered to express a human gene that causes early Alzheimer’s in humans. The vaccination halted production of plaques in the animals’ brains.

The researchers have also found that the peptides are not toxic to human neurons in tissue culture. They are thus hopeful that immunization with one of these peptides might prove to be both an effective and safe Alzheimer’s treatment in humans. They anticipate testing one or more of these peptides on Alzheimer’s patients starting in 2004.

Even if a beta amyloid vaccine does not prove to be a safe and effective treatment for Alzheimer’s, there may still be some other ways of reducing the plaque burden in the brains of Alzheimer’s patients and thus countering their disease, Nordberg pointed out. “There are a lot of ideas being pursued,” she added. For instance, some drug companies are attempting to see whether compounds that inhibit two enzymes involved in the production of beta amyloid might also counter Alzheimer’s. The enzymes of interest are called beta secretase and gamma secretase.

All in all, Nordberg said, beta amyloid continues to be of major interest to Alzheimer’s scientists throughout the world, “although we don’t really know whether it is the most important factor in the development of Alzheimer’s or not.”

More information about the cessation of the vaccine trial is posted on the Web at http://news.bbc.co.uk/1/hi/health/1836281.stm and www.the-scientist.com/yr2002/apr/steinberg_p22_020401.html. ▪