Inside the recesses of the brain, neurons carry a protein called amyloid, which researchers believe may play a crucial role in the onset of Alzheimer's. For reasons still not completely understood, the protein builds into a plaque in people who have the disease, amassing in certain regions of the brain and possibly disrupting signals between brain cells. Researchers are studying whether this may lead to symptoms of the degenerative brain disease that afflicts 4 million Americans -- more than 12% of the population over age 60.
Now, a tiny Australian company headed by one of the world's leading Alzheimer's researchers -- Colin Masters, medical professor at the University of Western Australia -- believes it may have accomplished something that a dozen of the largest pharmaceutical companies in the world have been unable to do. On Apr. 4, Melbourne-based Prana Biotechnology (PRNAF) announced clinical-trial results for its experimental compound, PBT-1, suggesting that the drug appears to lower the level of amyloid in patients' blood and slows the progression of the disease.
Prana's trials involved just 32 patients (16 actually took PBT-1), so it's way too early to be calling its results a major breakthrough. But the results are encouraging.
Alzheimer's has been a research priority for more than a dozen major drug companies. Treatments exist that slow the disease, but few human clinical trials to date have shown any compelling evidence of halting its progression outright, and Alzheimer's remains incurable. "What's out there as far as treatment options is nothing satisfactory," says Dr. Joseph Willner, chief of neurology at Englewood Hospital & Medical Center in New Jersey. "What we're really waiting for is a drug that arrests the disease or alters its course of progression significantly."
TWO CONCLUSIONS. So far, the outcome of Prana's small human clinical trial haven't been made public. The company is remaining quiet while it prepares to publish the results in a peer-reviewed journal. But Masters, chairman of Prana's scientific advisory board and co-founder of the company, announced two conclusions: First, the amyloid protein, which Prana's drug targets, was significantly reduced in the blood of patients in the treatment group compared to an increase in the group of patients who received a placebo.
More important, progression of the disease was slowed in the more severely affected patients in the treatment group compared to the placebo group. "Based on the safety and efficacy findings of this pilot study, we will structure additional clinical trials to move the drug toward commercialization," Masters declared at a Geneva medical conference.
Only a few months ago, Elan Pharmaceuticals, the creator of last year's promising Alzheimer's vaccine, stumbled hard when it learned that a small number of patients receiving the immunization had suffered brain inflammation. The company has postponed development as it tries to figure out what went wrong. Four federally approved drugs are on the market to treat the disease, including Pfizer's Aricept and Johnson & Johnson's Reminyl. But doctors say in most cases these drugs only temporarily slow the symptoms.
STOCK BOOSTER? Prana's drug must now undergo extensive human clinical trials involving hundreds of people with the disease, experts say. Despite that challenge, the initial trial adds strength to the belief that by influencing or blocking amyloid, scientists may be closer to understanding what causes the disease and how to conquer it.
If the initial results hold up and PBT-1 shows promise, it also could boost Prana's stock, which has has never traded above $2 a share and closed on Apr. 8 at $1.35. The company's research program is run by Masters, who was part of a team of scientists that in 1984 sequenced the chemistry of the amyloid protein. Prana is managed by Alzheimer's experts at Harvard Medical School and Massachusetts General Hospital.
If Prana is successful, its research could also dash assumptions that pharmaceutical companies need massive resources to develop an important drug. Prana has raised only $15 million since its inception in 1997. This little company Down Under has, at the least, sharpened interest in one of the most promising areas of Alzheimer's research. By David Shook in New York