New Alzheimer's Drugs on the Horizon
The treatments available to the more than 5 million people in the United States with Alzheimer's disease have been frustrating for patients and doctors alike. They treat only symptoms, not the underlying disease process that disables the brain. But after years of research, new treatments for Alzheimer's are getting tantalizingly close. There are now dozens of potential Alzheimer's drugs being tested in people and doctors are optimistic that within a few years patients will have drugs that can slow or actually reverse the disease.
The most eagerly watched drug, Alzhemed, has become tangled in unexpected problems in late-stage clinical trials. The drug is an oral medication that appears to prevent the formation of brain-tangling plaques by binding to beta-amyloid, a protein thought to be a key culprit in the brain damage typical of Alzheimer's. But the news from a big Phase III clinical trial of Alzhemed, presented Monday at the Alzheimer's Disease Prevention Conference in Washington, D.C., was disappointing. Results from the different cities where test subjects lived varied so much that the results were impossible to interpret, according to Paul Aisen, a professor of neurology at Georgetown University Medical Center who led the trial. (Phase III trials are the last stage of testing before manufacturers seek marketing approval from the Food and Drug Administration.) The patients were also taking standard Alzheimer's treatments, including acetylcholinesterase inhibitors and memantine. The researchers will go back to the lab and do more analysis to try to account for the differences. The Alzhemed trial involved 1,052 patients who took the drug or a placebo for 18 months. Sam Gandy, a neuroscientist at Thomas Jefferson University and chair of the Alzheimer's Association's medical and scientific advisory council, said the disappointing news will be helpful in designing trials for other Alzheimer's drugs in the pipeline.
Better news came from researchers testing Dimebon, a drug that was originally developed in Russia as an antihistamine. Researchers from Baylor College of Medicine reported Monday that their Phase II clinical trial with 183 participants found that patients with mild to moderate Alzheimer's taking Dimebon for one year did better on five measures of cognition and behavior, and seemed to be doing better overall, than those on placebo pills. The patients taking Dimebon maintained their abilities or improved their performance after 12 months, suggesting that the drug may do more than just alleviate symptoms, according to Rachelle Doody, a neurologist at Baylor who led the trial. Rather than attack beta-amyloid, Dimebon appears to slow brain cell death by working on mitochondria, tiny energy sources within cells that may play a role in neurodegenerative diseases and the aging process. The study participants were not taking other Alzheimer's drugs.
And there's a hint of hope about vaccines, too. In 2002, researchers halted a clinical trial of the first Alzheimer's vaccine after about 6 percent of the 375 volunteers with Alzheimer's developed brain inflammation. The vaccine, a synthetic form of beta-amyloid protein, was designed to trigger the body's immune system to create antibodies against beta-amyloid. Researchers tracked the health of 159 of the subjects for four and a half years, and found that the 25 patients who had built up an antibody response did better on memory tests, and were less dependent on their caregivers. Michael Grundman, senior director of Clinical Development in the Alzheimer's disease program at Elan Pharmeceuticals Inc., said Elan and Wyeth are now testing another vaccine they think will be safer and just as effective.