WASHINGTON - Preliminary results from the first human study of a possible Alzheimer's disease vaccine seem to show it is safe for patients, a pharmaceutical company announced Tuesday. Scientists said it is far too soon to tell if the vaccine will actually do patients any good.
Elan Pharmaceuticals' experimental vaccine raised tremendous excitement last year when the company showed that in mice the compound could ward off and even reduce the brain-clogging plaques that are a hallmark of Alzheimer's disease.
"Of course, mice aren't humans," cautioned Dale Schenk, Elan's lead scientist. Doctors inject a synthetic form of the naturally occurring beta amyloid protein to see if the body would develop antibodies against it. And that has been one of the longstanding questions about a vaccine, said Jerry Buccafusco, director of the Alzheimer's Research Center at Medical College of Georgia.
"Beta amyloid is obviously a natural constituent of cells all throughout the body, particularly in the liver and the brain," said Dr. Buccafusco, also a research pharmacologist at the Augusta Department of Veterans Affairs Medical Centers. "The question was, if your reduce the beta amyloid load in the body, does that have any serious consequences for normal function?"
Elan has begun small studies in people to see if the vaccine is safe. If so, the company hopes to launch larger studies, possibly by the end of 2001, to test whether the vaccine might slow progression of mild to moderate Alzheimer's disease - and maybe improve symptoms.
In the first safety results from those Phase 1 trials, none of the 24 Americans with early Alzheimer's who received a vaccine injection suffered side effects, Dr. Schenk said. "There's no question the vaccine was well-tolerated," he told an international meeting of 2,800 Alzheimer's researchers.
Now comes an important second step: Elan is enrolling 80 British patients with early Alzheimer's into another Phase 1 study and giving them three shots of the vaccine over several months. Their immune systems will be checked for early signs that the vaccine is strong enough to activate immune cells necessary to fight disease.
"We're all very excited about this but it is very early," said Dr. Ivan Lieberburg, Elan's chief medical officer.
"There's no question that this is a very exciting experiment for Alzheimer's disease," Dr. Buccafusco said. "It represents one of the very, very few opportunities we have right now to stop the disease in its tracks. We should be very cautiously excited about the potential at this point."
Although no one knows if the vaccine ultimately will help, the experiments are hopeful because they are grounded in years of basic research into just what role the brain-clogging amyloid plaques, actually play, said Alzheimer's Association vice president Bill Theis.
Alzheimer's disease afflicts about 4 million Americans. It starts with forgetfulness but relentlessly progresses to full dementia until finally killing its victims. The three available drug treatments provide only partial relief for a short time.
Patients' brains are full of sticky amyloid plaques. It is not clear if the plaques cause Alzheimer's disease or are a result of it. Regardless, studies show they lead to the death of brain cells.
The plaques' main ingredient is beta amyloid, a fragment of a normal body protein that somehow goes awry in Alzheimer's. Some patients produce too much beta amyloid and others simply do not clear it out of the brain properly.
Elan theorized that a vaccine made from beta amyloid would stimulate the immune system to recognize and attack the protein.
Indeed, vaccinated mice developed immune system antibodies that traveled to the brain and "tagged" amyloid plaques. That tagging seems to alert microglial cells, which Dr. Lieberburg calls the brain's "garbage-men," to head for the plaques and try to eradicate them. Upon dissection, the brains of vaccinated mice contained no or very small plaques while their unvaccinated littermates had extensive plaques.
Another study unveiled at the Alzheimer's meeting supports Elan's work. University of Toronto scientists taught mice bred to develop an Alzheimer's-like disease to swim through a water maze. Over several months, vaccinated mice remembered how to get through the maze far better than unvaccinated mice, promising evidence that the vaccine may affect symptoms, not just plaque.
Elan Pharmaceuticals is a South San Francisco, Calif., subsidiary of Ireland's Elan Corp.
Staff Writer Tom Corwin contributed to this article.