The frustrating search for Alzheimer's treatments

The leading Alzheimer's drug discovery strategy being pursued by companies including Wyeth and Elan Corp. appears increasingly risky as new studies emerge.

More than a dozen drugs now in human testing were designed to slow progression of the illness by blocking the proteins that form clumps in the brain. While the medicines may reduce the levels of this substance, they have shown little sustained ability to improve memory or mental function. And a more complex picture is emerging from laboratories: the beta amyloid protein that scientists think kills neurons isn't always bad.

"Drug companies are betting billions that beta amyloid is a cause of Alzheimer's, and I desperately hope they are right," Paul Rosenberg, assistant professor of psychiatry at Johns Hopkins University School of Medicine, said. "My optimism is somewhat tempered because I'm not sure our hypothesis is really solid."

Treatments are urgently needed as the number of dementia patients worldwide is expected to swell to 120 million by 2050, according to Anders Wimo, professor at the Alzheimer's disease Research Center at Karolinska Institute in Stockholm. In the U.S., almost 73,000 people died from the illness in 2006, a 47 percent increase in just six years, according to the Alzheimer's Association. Now, no drugs can stop the disease.

At a recent International Conference on Alzheimer's disease in Vienna, researchers announced setbacks with experimental treatments from GlaxoSmithKline Plc, AstraZeneca Plc, Martek Biosciences Corp., Johnson & Johnson, Abbott Laboratories and Myriad Genetics Inc. All failed to improve symptoms or slow the disease.

"Despite 20 years of really committed approaches to new therapies, it has not proven easy to develop new standard-of-care treatments," said Randy Schiffer, director of the Cleveland Clinic Center for Brain Health. "Everybody is frustrated about that. Maybe we're starting these trials too late, maybe we don't fully understand the disease, maybe we're not following people long enough. It's a matter of concern to all of us."

After these failures, the most highly anticipated therapy is Dublin-based Elan and Wyeth's bapineuzumab. Elan and Madison, N.J.-based Wyeth have begun the final phase of testing and data from the trial "may be available in the second half of 2010," Elan spokeswoman Niamh Lyons said.

"Everyone is waiting with bated breath on bapineuzumab," said Michael Gold, London-based Glaxo's vice president of neurosciences. "If that one fails, then everyone will say we have to rethink the amyloid hypothesis."

Bapineuzumab showed no benefit for most patients in an earlier study, though it slowed memory loss better than existing treatments for those without a genetic predisposition to the disease. The final trial groups patients based on genetic makeup to pinpoint how people respond to the drug.

The amyloid hypothesis is a leading theory for how Alzheimer's disease develops and progresses. Named for the protein that is the main component in the plaques found clogging the brains of patients during an autopsy, recent scientific findings show it's an active molecule with some beneficial properties.

Researchers studying beta amyloid found it may be a byproduct of the synaptic transmission that's essential for learning and memory. Advanced imaging technologies that accurately measure amyloid in the brain find up to 20 percent of the elderly with no memory problems have amyloid plaques.