Another once-promising Alzheimer's treatment goes down the tubesS

It's bad enough news that Eli Lilly & Co. pulled the plug on an experimental Alzheimer's Disease drug, semagacestat, after dreadful clinical trials. But Lilly's failure makes it more likely Alzheimer's treatment research has been going down a blind alley.

It's been over a hundred years since Alois Alzheimer first discovered excess proteins in the brains of people with senile dementia, in autopsies. We now know there are two types of proteins that show up — there are plaques, made out of a protein called beta-amyloid, which clog up the brains of Alzheimer's sufferers, and then there are "tangles" of a protein called tau, which are found in the neurons of Alzheimer's brains. For years now, drug companies have been pouring all of their resources into creating drugs that reduce the beta-amyloid plaques. Some researchers argued that tau tangles were more important, and a newer generation of drugs will target Tau more than beta-amyloid.

The good news is that drugs that reduce beta-amyloid plaques do seem to reduce Tau tangles as well, as researchers announced jubilantly at last month's Alzheimer's conference.

The bad news is that Lilly's failed drug, which targets beta-amyloid plaques, didn't improve patients' cognition at all, and it actually reduced the patients' ability to perform daily activities. And the early indications are that other drugs in the pipeline that focus on beta-amyloid plaques may not be any more successful. One of the leading contenders, Pfizer and Johnson & Johnson's bapineuzumab, showed a clear reduction in beta-amyloid plaques (and tau tangles), but failed to demonstrate any clear improvement in mental functioning, according to a March 1 study.

Dr. Gary Kennedy, director of geriatric psychiatry at Montefiore Medical Center in New York City, put it most succinctly at the July Alzheimer's conference, when he said both beta-amyloid and tau "may be manifestations of the disease and not its origin."

Dr. Allen Roses, director of the Deane Drug Discovery Institute at Duke University Medical Center, tells Bloomberg:

Alzheimer's research has overemphasized the amyloid hypothesis for a very long time. When the leading candidates for Alzheimer's disease appear to fail for one reason or another, to me it's simply evidence that the hypothesis is not right.

Bloomberg also did talk to some other people who stand by the "amyloid hypothesis," and a few drug companies continue to push forward with drugs that target beta-amyloid, including bapineuzumab.

Unfortunately, because of the long lead time involved in drug development, even as it starts looking more likely that focusing on these proteins may have been a mistake, it could still take several years before we start seeing new experimental drugs that are based on a different approach. The good news: researchers think they've isolated just four genes that are linked to half the cases of Alzheimer's, and drugs that target those genes might show more promise. [Bloomberg]