New Treatments for Alzheimer's on the Horizon
WEDNESDAY July 15, 2009 -- New interventions show promise against two different types of brain abnormalities, both of which are implicated in the development and progression of Alzheimer's disease.
A drug called Dimebon seems to improve cognitive function in both mice and humans but, new research reveals, it actually increases brain levels of beta amyloid, a protein long thought to be a leading culprit in the development of Alzheimer's disease.
Meanwhile, a vaccine has had some effect in reducing the number of tau protein tangles that are also associated with Alzheimer's.
Both studies were to be presented Wednesday at the Alzheimer's Association annual meeting, in Vienna.
Beta amyloid is the main "ingredient" in the amyloid protein plaques that are hallmarks of Alzheimer's disease. Drug companies around the world are racing to find compounds that can reduce brain levels of beta amyloid.
The drug used in this study is dimebolin (Dimebon), described in the research abstract as a "retired Russian antihistamine."
Right now, researchers aren't sure what to do with the findings.
"This is a very surprising and unexpected result," said study author Dr. Samuel Gandy, associate director of the Alzheimer's Disease Research Center at Mount Sinai School of Medicine in New York City. "Virtually every major pharmaceutical company and many academic labs are working on amyloid-lowering drugs, and along comes the most clinically promising drug ever [at least according to the data published in The Lancet last year], and it actually raises amyloid levels," Gandy said.
"This will definitely tell us something previously unsuspected about either a novel drug target or about amyloid metabolism," Gandy continued. "Unraveling this story will change how we think about Alzheimer's drugs, how we think about amyloid, or both."
It could be that Dimebon neutralizes then expels the excess amyloid from the brain, or that there is actually some benefit to having amyloid outside the neuron as opposed to inside (where it might be more toxic), Gandy postulated.
And it's entirely possible that beta amyloid is not the main culprit in Alzheimer's. "It's not clear that amyloid is what's toxic to the neurons and it may be that Dimebon is mobilizing the stuff to get it out of the system," said Dr. Gary Kennedy, director of geriatric psychiatry at Montefiore Medical Center in New York City. "Amyloid may be a nasty traveling companion rather than the assassin."
There has been no hint yet that the elevation in beta amyloid levels produces undesirable side effects.
Pharmaceutical companies are working aggressively to move this drug towards a U.S. Food and Drug Administration approval, said Dr. Ralph Nixon, vice chair of the Alzheimer's Association Medical & Scientific Advisory Council.
"Especially if the drug is confirmed to be efficacious in Phase 3 trials, I think this will be a very strong tool to find clues as to what the basic cause of the disease is and some of the factors leading to the development of Alzheimer's," Nixon said. "Some of those factors may be independent of beta amyloid but it's too early to say that. But it certainly raises some interesting thinking about possible other factors that might be targetable as new drug therapies."
A second study found that a vaccine that targets the neurofibrillary "tau" tangles seen in Alzheimer's brains did actually reduce levels of the structure, at least in mice.
Until now, researchers haven't had much success with amyloid immunization or even with previous experiments with tau vaccines, which have caused brain inflammation in past research.
The Israeli researchers immunized mice who had been genetically engineered to develop neurofibrillary tangles with a combination of three phosphorylated-tau peptides, or shortened versions of the protein.
They saw about a 40 percent reduction in the number of tau tangles, with no evidence of brain inflammation.
"There's certainly a great deal of support for tau being very intimately involved with the disease and, although people kind of pit one against the other, I think, at the end of the day, they're going to be relatable through a common mechanism," Nixon said. "We may be beyond the point of thinking it's going to be either/or. It's going to be both and both potentially will be targetable sites."
In related research, scientists from the University of California at Los Angeles and Riverside, along with colleagues from the Human BioMolecular Research Institute, found that a form of vitamin D, when combined with a chemical found in a spice called curcumin, may help stimulate the immune system to clear the brain of amyloid beta.
Reported in the July issue of the Journal of Alzheimer's Disease, the findings could lead to treatments for Alzheimer's that tap into the powers of vitamin D3, either with or without curcumin.
Visit the Alzheimer's Association for more on this condition.
Posted: July 2009