While the vaccine bolstered cognitive skills in a mouse model of Alzheimer's, some researchers are concerned it may trigger an uncontrollable immune response in humans, however. Nevertheless, preliminary human trials testing safety of the vaccine are underway in the United States and England.
Using mice genetically altered to mimic symptoms of the debilitating disease, investigators found that vaccinated mice were able to learn and remember skills as easily as normal mice -- and far better than genetically-altered mice injected with a placebo vaccine.
While a number of Alzheimer's researchers heralded the studies as a good omen for human trials, the vaccine approach remains controversial. At the same time, most experts agree the studies strengthen the emerging consensus that beta-amyloid - a small, mistakenly formed protein in the brain - is the cause of the disease.
For example, researchers didn't know until now whether aging Alzheimer's mice suffered mental problems akin to those in humans, even though previous research demonstrated the mice build up plaques, or deposits of beta amyloid in the brain, just as people do. One of the Nature studies, by Dr. Richard Morris of Edinburgh University and his colleagues suggest the mice do suffer such mental deterioration.
The other two papers, by Canadian and American research groups, report vaccination with the beta amyloid protein appears to slow the process.
"For ten years, we have explored the hypothesis that beta amyloid causes the disease, praying and hoping that if we could reduce the plaques, we could improve cognition, but these studies are the first to really link hypothesis to changes in cognitive function," said Dale Schenk, a vice president at Elan Corp., San Francisco, who developed the beta-amyloid vaccine used in both the Nature studies and the phase one human trials.
Schenk published a paper in Nature last year that showed the vaccine reduced plaques in the brains of mice, but he did not address the question of impact on cognition.
Some researchers have believed the plaque formation represented the body's way of coping with toxic levels of beta-amyloid -- and thus removing the plaques would impair, not bolster, cognitive function. David Morgan, lead investigator on one the vaccine Nature studies, actually undertook his study with that hypothesis in mind.
"I was sure that the vaccine would ultimately worsen cognition and memory problems. We were completely surprised when the reverse occurred, " said Morgan, director of the Alzheimer's Research Laboratory at the University of South Florida, Tampa. "What we and the others have found is that vaccination at least partially protects against memory loss in the vaccinated mice," though "it remains to be seen how robust that protection is."
No one really knows why the vaccination appears to slow mental deterioration in the mice or what the ultimate long-term benefits or harms of the vaccination might be.
Morgan began injecting the study mice monthly, beginning at seven months. At fifteen months - which is, in a mouse, roughly the equivalent of a human age of 55 - the researchers first noticed that the vaccinated mice performed better at a critical memory task than the mice injected with placebo.
The mice were euthanized at that point to study their brain tissue, so prospective evaluation of their condition was impossible. Morgan and others are proposing to do further research that would include follow-up of the mice beyond the study endpoints.
But when it comes to humans, some Alzheimer's researchers voice a concern that vaccination is different and thus may be the risks as well.
"These mice are being vaccinated with a human protein. For humans being vaccinated with a human protein, there is a possibility that you are inducing an autoimmune response," said Dr. Ashley Bush, associate professor of psychiatry at Harvard University Medical Center, a leading investigator in the role of beta-amyloid in Alzheimer's disease.
The fear is that vaccination against beta-amyloid will, over time, spawn a legion of antibodies that will attack the larger protein of which it is a critical part, the so-called amyloid precursor protein.
"When a patient has an adverse reaction to a drug, you can stop the drug and the reaction stops. But if patient has an autoimmune response, or other adverse consequence from a vaccine, you can't stop it in the same way. The vaccine has been given and the response has been mounted," explained Bush.
Elan's Schenk acknowledges the potential risk has been considered in the human trials. But when asked if any of the human subjects have been found to have an immune response directed against the amyloid precursor protein, Schenk declined to comment.
"That data have not yet been presented and I can't give you an answer right now," he told United Press International.
Morgan agrees that the risk of auto-immune reaction is a serious consideration. He suggests that perhaps rather than vaccinate with the protein itself, an alternative might be to simply inject antibodies directed against the protein and follow the effects.
He does note that researchers have injected mice with the vaccine for about half the animals' lifetimes and noticed no serious adverse affects.
Whatever the ultimate role of a vaccine in the treatment of Alzheimer's disease, the group of studies are widely regarded as shedding new light on the role of beta-amyloid and potential therapies.
"The most important thing is that the studies involve a therapy targeted at the very molecule that causes the disease. Currently available therapies just treat symptoms," said David Westaway, a molecular biologist at the University of Toronto and co-author of one of the papers in Nature.
"If the vaccine approach doesn't ultimately work against the peptide, there are others that involve a different strategy," Westaway said. "Some attempt to stop the peptide's production, or decrease the formation of plaques, or simply reduce beta-amyloid's toxic effects. These studies are just one more step toward understanding the disease and ways to treat it."
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