July 17, 2008 — -- A pill once used as an antihistamine in Russia has shown a slight but unique promise for treating Alzheimer's disease and is now on a fast track to drug studies in the United States.
The drug, called Dimebon, appeared to slow memory loss in patients with mild to moderate Alzheimer's disease. But, unlike current Alzheimer's therapies, Dimebon also slightly improved memory. In another first, Dimebon's effect continued for more than a year, while current Alzheimer's treatments are known to peak at three or six months and then begin to lose their effects.
Yet the results from the study of 155 patients in Russia have left many Alzheimer's experts only cautiously optimistic until larger, longer studies are completed under the Food and Drug Administration.
"The Alzheimer's community has been here before with other drugs only to be disappointed," said Dr. Lon S. Schneider, professor of psychiatry and behavioral sciences at the University of Southern California Keck School of Medicine in Los Angeles. Schneider noted the same Dimebon results that appear in this week's medical journal, Lancet, also were released to scientists a year ago.
"There's not much to do except wait for the Phase III trial to be completed," Schneider said.
The race to find a good Alzheimer's treatment has been full of high hopes and devastating failures. At present, there is nothing to cure or stop Alzheimer's. In the current issue of Lancet, doctors also report that a once-promising vaccine shown to clear plaque in the brain associated with Alzheimer's has had little effect on the symptoms of memory loss.
Still, an American doctor who conducted the Russian study was heartened by the preliminary results. Patients showed improvements across five measures of mental, emotional and physical abilities. The side effects included dry mouth and reported depressed moods.
Participants in the study, half on placebo and half on Dimebon, were given two mental and memory tests, questioned about everyday skills such as dressing, asked about their anxiety and finally were interviewed by a separate doctor in a "clinician's global measure."
"It's what your doctor would really see," said Dr. Rachelle S. Doody, lead author of the Dimebon study and director of the Alzheimer's Disease and Memory Disorders Center Baylor College of Medicine in Houston.
"For us to be able to see not only a positive signal, but a signal on all five measures is very reassuring and hopeful," Doody said. Dimebon also improved patients' scores by an average of two points on a 70-point scale of mental functioning.
When compared to the patients on placebo who were declining, patients receiving Dimebon scored an average of seven points higher on the scale. Those seven points account for a real-world equivalent of slowing memory loss by one year, according to the Aging Research Center.
But doctors, including Doody, don't know exactly how Dimebon works, which leaves questions about how the drug might interact with current Alzheimer's medications and even measure up to them.
"The effect was strong but absent a direct head-to-head comparison it might be a bit too much to say that Dimebon blows the competition out of the water," said Karl Herrup, chair of the Cell Biology and Neuroscience Department at Rutgers University in Piscataway, N.J.
"The question would be whether it has an additive effect if it were administered along with current medicines," Herrup said. "Since it may be acting through the same pathways, there may be no added benefit."
Dr. Doody's team originally thought Dimebon worked in the same way as the two main types of Alzheimer's drugs &$151; cholinesterase inhibitors and NMDA-receptor antagonists. But now Doody suspects Dimebon might functions differently.
"This drug does both of those functions, but weakly," Doody said. "We think that those two drug actions are really not important to why it was successful."
Instead, Doody believe Dimebon's action centers around mitochondria — the so-called power plants of cells — keeping brain cells functioning, maintaining communication between brain cells and potentially protecting them from death. Yet all of that still only treats the symptoms of Alzheimer's.
"This drug and all the others are not cures for the disease," Doody said. "This is promising … but it's not marketed anywhere in the world right now, and it hasn't been approved in any country."
Doody and her team are recruiting for a six month, Phase III FDA trial in the U.S., Europe and South America. The results of that trial will determine whether Diebon moves on to the the FDA drug approval process.