Scientists are encouraged by studies that show the vaccine works even in mice genetically engineered to get the disease.
By WES ALLISON
© St. Petersburg Times, published December 21, 2000
TAMPA -- Last year, as he planned the experiment, Dr. David Morgan figured the Alzheimer's vaccine he was about to test could never work. Not only would it fail to help, he firmly believed, it would make the disease even worse.
What he and other researchers at the University of South Florida found, however, was quite the opposite.
On Wednesday, the USF team and another group from the University of Toronto published separate studies in the journal Nature that showed the vaccine stopped or slowed Alzheimer's in mice that had been genetically engineered to get the disease.
Those vaccinated mice also performed just as well as normal mice on a memory test, while their unvaccinated brothers and sisters hopelessly foundered, the USF study found.
Although many questions remain, national Alzheimer's experts say the findings are highly encouraging, and they suggest the vaccine could lead to a treatment for the disease, which is unstoppable today. Preliminary trials in humans are under way.
"I think it bodes well, especially for people with early stages (of Alzheimer's), or for people who are predisposed," said Morgan, a professor of pharmacology and the study's lead investigator. "We started out trying to shoot this thing down, and we found the exact opposite. And that convinces me that what we found was real."
The USF and Toronto studies were performed independently, with no financial or technical support from Elan Pharmaceuticals or American Home Products, which are developing the vaccine and have begun testing its safety in people.
Alzheimer's disease is progressive and debilitating, and anything that slows it would be seen as a godsend to the 4-million Americans, including 400,000 Floridians, who have it. In the greater Tampa Bay area, some 90,000 people have been diagnosed with it, according to the Alzheimer's Association.
"For our families, any type of news that encourages people, that gives people hope, does wonders," said Gloria J.T. Smith, executive director of the association's Tampa Bay chapter.
But, she added, "It's kind of a mixed blessing when you get these kind of breakthroughs. The process can be very long, the FDA approval can be even longer. We want to be optimistic, but we still have to be realistic."
Typically, a vaccine is made of small amounts of a virus or other organism, such as polio or influenza, that will kick the body's immune system into action and trigger immunity to that disease.
The Alzheimer's vaccine appears to work much the same way. It consists of beta amyloid protein, which creates plaque in the brains of Alzheimer's patients and increasingly is thought to play a role in the development of the disease.
In the mice, the vaccine stimulated immune system antibodies that found their way to the brain, then eradicated amyloid plaques or kept them from forming there.
This was surprising, because many researchers believed activating the immune system would cause more inflammation in the brain, leading to further brain damage and memory loss.
"I think we all were shocked," said Dr. Stephen Snyder, an Alzheimer's researcher at the National Institute of Aging, which supported the USF research with a $2.2-million grant.
Wednesday at his USF office, cluttered with scientific journals and pictures of his kids, a rubber brain on the desk before him, Morgan said he embarked on the experiment in August 1999 after reading about Elan's vaccine in Nature.
In that account, the company's scientists said the vaccine reduced the buildup of amyloid plaques in the brains of Alzheimer's mice, and they theorized it also would preserve their memory.
The Elan researchers, however, could not prove that; their mice simply weren't smart enough to handle a sophisticated test that measures memory. USF's genetically altered mice were, however, and Morgan set out to prove Elan's theory wrong.
At USF, he worked with Dr. Gary Arendash, a biologist, and Dr. David M. Diamond, a behavioral psychologist, to develop the test. Dr. Kenneth E. Ugen, an immunologist, concocted the vaccine based on Elan's published work.
Their experiment involved three groups of seven mice: One group was genetically engineered to get Alzheimer's and was given the vaccine; one was genetically engineered but not vaccinated; and the third, a control group, had no disposition to Alzheimer's.
All were taught to negotiate a water maze to find an underwater platform, and at 12 months of age they all could do it equally well.
By 15 months, however, the unvaccinated Alzheimer's mice could not find the platform, even after five tries. Their vaccinated brothers and sisters could. Over five tries, they performed as well as the mice in the control group.
At autopsy, Morgan found the vaccinated mice had less amyloid plaques than the unvaccinated ones. And while their brains had become inflamed to some degree, it didn't seem to matter.
A Nature editorial accompanying the articles said the findings also add to the understanding of the dementia that Alzheimer's patients suffer. Some researchers suspect it's caused by the amyloid plaques, while a competing theory suggests that something else is to blame, and the amyloid is simply a byproduct.
"So it is significant that (researchers) found that simply hampering the formation of amyloid plaques is sufficient to prevent the decline of learning and memory," the editorial said.
The USF researchers now hope to learn if the vaccine can reverse existing memory loss in Alzheimer's mice. They also want to know how long the vaccine keeps working.
"I think this may be a very good, very useful, very strong treatment model, but I think it's early days yet," Snyder said. "There are going to be many more years worth of studies to try to understand how we can best treat humans using this approach. The vaccine approach has eradicated lots of killer diseases in the past."
Here are some facts about Alzheimer's disease -- a progressive, degenerative disease of the brain.
Alzheimer's affects about 4-million Americans.
One out of every 10 people over the age of 65 have Alzheimer's.
A person with Alzheimer's lives an average of eight years and as many as 20 years from the onset of symptoms.
The federal government devoted nearly $500-million to Alzheimer's research this year.
USF team finds gene link to Alzheimer's (September 26, 2000)
Altered cells may repair brain damage (August 2, 2000)
Seniors gain access to new treatments (June 8, 2000)
Alzheimer's team touts discovery (December 17, 1999)