Why There’s Real Reason to Hope

Photo by TS Photography/Getty Images

Today we conclude our special report on the international Alzheimer's conference in Chicago with news of two drugs that offer new hope.

From two "landmark" medicines that target Alzheimer's in a totally new way to an antihistamine drug that improves thinking and memory in patients with the disease, researchers reported some encouraging results at the international conference on Alzheimer’s, which ended yesterday.

During the four-day conference, scientists unveiled the latest Alzheimer's research, including two promising new therapies that for the first time successfully target "tau," the tangles of protein that form inside the brain cells of people with Alzheimer's. Although the cause of Alzheimer's is still unknown, many researchers have been at work on drugs that target beta-amyloid, a protein that forms sticky plaque on the outside of the brain cells. While both tau tangles and amyloid plaque are hallmarks of Alzheimer's, researchers have repeatedly shown that when plaque is reduced in the brains of mice with Alzheimer's, the mice can solve problems and run mazes that once confounded them. It’s taken longer, one expert says, to come up with drugs that affect the tangles and less is known about their role in the disease.

While researchers still believe that amyloid is an underlying cause of Alzheimer's, "I think having the first two antitangle medicines is a real landmark," says Sam Gandy, M.D., chair of the national Medical and Scientific Advisory Council of the Alzheimer's Association. The association organized the conference in Chicago.

"Our evidence," he says, "is that tangles form earlier than plaque. So it could be that a cocktail of antitangle and anti-amyloid drugs will be the most effective therapy."

Here then are highlights of some of the most promising drug studies reported at the conference:

Rember: Researchers in Great Britain found that a drug that directly targets tangles in the brain cells of Alzheimer's patients was able to slow the progress of the disease by as much as 80 percent. In phase II tests with 320 people over a 50-week period, the drug Rember was more than two and a half times as effective in treating the symptoms of Alzheimer’s as Aricept, one of the few medications available for the disease.

The new drug helps dissolve the tangles. "Our results show it may be possible to arrest the progress of Alzheimer's disease by targeting these tangles," says Claude Wischik, M.D., of the University of Aberdeen, Scotland, who did pioneering research with tau and is now working on Rember trials. "This is an unprecedented finding."

 He says the drug also may slow the brain's deterioration. Rember will be tested in larger clinical trials that should get underway in 2009.

AL-108: This drug, which reduces the tangles in the brains of mice, was found to improve some kinds of short-term memory when tested in a 12-week study of 144 patients with mild cognitive damage (MCI)—a precursor to Alzheimer's. Men and women with MCI have memory problems but do not exhibit the confusion, attention problems or difficulty with language that characterize Alzheimer's. The nasal spray drug's positive results add to the growing interest in tau as a key actor in the Alzheimer's drama. Donald Schmechel, M.D., a researcher at the Duke University Medical Center, Durham, N.C., says the findings suggest tangles "may be as important—or perhaps more important—than plaques."  Further studies are planned.

	Relationships Do Matter in Fending Off Alzheimer’s
	New Tests for Early Detection
	Excerise May Slow the Ravages of  Alzheimer’s
	Drug Offers a Ray of Hope for Alzheimer’s Patients

Dimebon: Already hailed as a breakthrough drug earlier this month, when the results of a year-long study were reported in the Lancet medical journal, this antihistamine continued to impress researchers when the study was extended for another six months. The drug improves thinking and behavior in people with mild to moderate Alzheimer's and sustains those improvements for at least 18 months, researchers say. The few drugs available today to treat Alzheimer's only tend to stabilize impaired memory, so Dimebon is considered a real advance. Patients are now being screened for large phase III studies, which should be completed next year. If those are successful, experts predict this will be the first new treatment for Alzheimer's, and it could be on the market as early as the end of 2010. Dimebon appears to work by improving mitochondria, the powerhouse of the cell that creates the energy it needs to carry out all its functions. "Impaired mitochondria may play a significant role in the loss of brain cell function in Alzheimer's," says Jeffrey L. Cummings, M.D., a researcher on the study who is director of the Mary S. Easton Alzheimer's Disease Research Center at the University of California at Los Angeles.

PBT2: The drug prevents amyloid from interacting with copper and zinc, which have been shown to play a role in the process that "clumps" amyloid protein into sticky plaque. Not only was the drug well tolerated, but patients showed improvement in two tests of verbal and reasoning abilities. Those same abilities deteriorated in the group given a placebo. The next step is another small trial to determine the most effective dose of the drug, then larger clinical trials to test its effectiveness, says Cummings, who worked on this study. “The results indicate PBT2 is having an impact on the underlying biology of Alzheimer’s, which is very exciting," Cummings says. “I am very hopeful but cautious.”

To find out about enrolling in a clinical trial go to www.clinicaltrials.gov.