Alzheimer's Cure No Longer Science Fiction, Experts Say

All things considered—for example, that there is still no simple diagnostic test for Alzheimer's disease and that medical science tends to advance slowly—the progress being made toward finding a cure for Alzheimer's is impressive.

This message was delivered by three leading Alzheimer's scientists at a public symposium held in Washington, D.C., in June.

The scientists were Marilyn Albert, Ph.D., a professor of neurology at Johns Hopkins University and co-director of Hopkins' Alzheimer's Disease Research Center; Allan Levy, M.D., Ph.D., chair of neurology at Emory University and director of Emory's Alzheimer Disease Center; and Richard Mayeux, M.D., a professor of neurology, psychiatry, and epidemiology at Columbia University and co-director of Columbia's Taub Institute for Research on Alzheimer's Disease and the Aging Brain.

The symposium was sponsored by the Dana Foundation, a nonprofit foundation that supports research in and public understanding of neuroscience, immunology, and arts education. The symposium was hosted by William Safire, a former political columnist for the New York Times and currently chair of the Dana Foundation.

During the 1980s, the nerve transmitter acetylcholine was found to be deficient in the brains of persons with Alzheimer's, and this discovery in turn led to the development of drugs for the disease that increase acetylcholine in the brain, Albert reported. Four such drugs are available on the U.S. market, but they “all appear to have approximately the same effect,” that is, to provide temporary symptom relief, but they do not prevent the disease's progression, she said.

They are able to counter Alzheimer's only over the short term, Albert noted, most likely because the cause of the disease is not acetylcholine deficiency, but the buildup of amyloid plaques in the brain. This is what most Alzheimer scientists think is the cause, she said.

The general belief of how amyloid causes Alzheimer's, Albert explained, is that amyloid protein is overproduced in the brain and leads to the formation of amyloid plaques. The plaques lead in turn to the formation of tangles, and those tangles lead to the death of nerve cells. Furthermore, Mayeux pointed out, all five genes implicated in Alzheimer's to date—APP, PS1, PS2, SORL-1, and APOE—“affect the processing or production of amyloid in some way.” For example, scientists do not know how the variant of the APOE gene that has been linked with Alzheimer's—the e4 version — works, Mayeux said, “but we do know that it enhances amyloid production.” The variant may also influence how the brain clears itself of amyloid, Levy added.

And as the evidence supporting the case that amyloid causes Alzheimer's becomes more credible, it is sparking the development of drugs that can counter amyloid plaques in the brain. Or as Levy put it: “Now we have a roadmap for how we can create rational therapies for Alzheimer's.”

For example, drug companies have come up with a handful of drugs that can block the enzymes that make amyloid plaques, Levy said. “This is a very exciting area.” Some drugs have also been developed that keep amyloid from clumping.

Indeed, a number of anti-amyloid drugs for Alzheimer's are now in phase II or phase III clinical trials, Albert reported.

For instance, the drug Alzhemed from Neurochem Inc. has just finished a phase III trial. Data are being analyzed. The drug Ly450132 from Eli Lilly and Company is entering a phase III trial. Elan Pharmaceuticals Inc. has announced that it is going ahead with a phase III trial for its drug AN 1792, a monoclonal antibody vaccine that clears amyloid from the brain. Myriad Genetics Inc. has presented encouraging data regarding its drug Flurizan; a one-year extension of its phase II trial led to the stabilization of Alzheimer's symptoms. And a promising drug has been developed by the Russian Ministry of Health. It inhibits the action of the NMDA (glutamate) receptor in the brain and improves the function of mitochondria in brain cells. Phase II trial results with it look very good, said Albert.

“Could it be that the Russians are ahead of us?” Safire quipped. Then he asked more seriously: “When will we find a cure for Alzheimer's?”

None of the scientists present was willing to give a specific time frame.

However, Mayeux did say he is “reasonably optimistic” that a cure will be found because the drugs now being developed to treat Alzheimer's are based on what appears to be the true biological basis of the disease.

To which Levy added: “We are not going after only one big fish,” so there is a good chance that at least one of the drugs being developed will prove effective against the disease. ▪