SUNDAY, March 16, 2003 (HealthDayNews) -- In possibly the first case report of its kind, researchers have found an experimental vaccine for Alzheimer's disease did wipe out the structures that are the hallmark of the condition, but apparently also caused the patient's brain to swell.
The 72-year-old woman studied was one of 360 Alzheimer's patients involved in a clinical trial of the vaccine, which was halted after 15 people developed brain swelling. The woman actually died of a pulmonary embolism a year after her last dose of the vaccine, which allowed researchers to autopsy her brain for clues on the vaccine's effectiveness.
Most of the amyloid plaques, which are protein clusters whose buildup appears to cause Alzheimer's, had been cleared from the woman's brain, although other evidence of the disease remained, they found.
"In that sense, it looks exactly as you predicted it might from previous studies of mice," says Dr. James A.R. Nicoll, the lead author of a report on the case in the April issue of Nature Medicine and a professor of neuropathology at Southampton General Hospital in the United Kingdom.
On the other hand, it appears the vaccine, known as AN-1792, may also have caused meningoencephalitis, or swelling of the brain.
Although the report deals with only one person, it could prove useful in pinpointing the future direction of research on this devastating disease, which currently affects 4 million Americans.
"It's the first-ever report of its kind," says Bill Thies, vice president for medical and scientific affairs at the Alzheimer's Association. "It's very important from the standpoint that it leads us to believe that there has been a change in amyloid accumulation in a living person. That's something that no one has been able to demonstrate before. I think that this is just the leading edge that's going to come from that trial."
Although numerous changes have been noted in the brains of patients with Alzheimer's disease who have died, scientists are not sure which of the changes are responsible for the loss of memory and other cognitive deficits that are classic symptoms of the disease. In recent years, much research has focused on the amyloid structures as the likely cause.
That's why this new research is so important, according to Thies. "If you look across the spectrum of Alzheimer's investigators, half or more work is on amyloid. And if that's not going to be a fruitful pathway, we ought to make some adjustments," he says. "We're trying to find out if this is the right way to go."
Because the woman died, one of the pivotal questions in Alzheimer's research remains unanswered.
"While the vaccine was effective in perhaps limiting amyloid accumulation, we don't know whether it had any effect on disease process, and that's a very important question," Thies says.
According to the researchers, the woman received her first injection in July 2000. That dosage was repeated four, 12 and 24 weeks later with no apparent problems. She received a fifth injection with a different dosage 36 weeks after the first injections. Six weeks later, she developed dizzy spells, drowsiness, fever and an unstable gait.
The woman died in February 2002, a month after researchers decided to halt the trial, which was conducted in Europe and the United States. The remaining trial participants are being carefully followed and evaluated, and Thies estimates that their data will be analyzed sometime this summer.
"We do know from some work that's been reported from a couple of the centers that were part of the trial that a portion of the people who are in the trials seem to be still busily making antibodies to amyloid, which is the way we think this treatment works," Thies says.
Meanwhile, researchers involved in the trial are trying to come up with ways to eliminate the side effects of AN-1792.
"Immunologists seem quite confident that it will be possible to develop an approach that gives the good affect of removing the plaques without the bad affect of the inflammation," Nicoll says. "They seem quite confident that they can modify the substance that is injected and get the good without the bad."
And if that happens, still one more question needs to be answered: Can that or any vaccine, given to younger people, actually prevent Alzheimer's from developing?
That remains the holy grail of Alzheimer's research.
More information
For more information, visit the Alzheimer's Association or the National Institute of Neurological Disorders and Stroke.
