THURSDAY, Sept. 21, 2006 (HealthDay News) -- Some bad news has emerged from a study of an enzyme that is a major target in the effort to find new drugs to fight Alzheimer's disease.
Beta-secretase plays an important role in development of the protein clumps called beta-amyloid that form in Alzheimer's disease and damage mental function, so researchers are looking for compounds that might inactivate it.
But now, scientists in Germany, Belgium and the United States report in the Sept. 21 online issue of Science that beta-secretase is also involved in myelination, the formation of a protective covering for nerve cells early in life. Interfering with that activity could cause lifelong nerve damage, the researchers speculated.
The report is "a cautionary tale for scientists developing drugs today," but hardly a death blow to overall drug development for this neurodegenerative disorder, said Dr. Sam Gandy, director of the Farber Institute for Neurosciences in Philadelphia and chairman of the Alzheimer's Association medical and scientific advisory council.
The study was done in infant mice, when the protective covering forms, and "there may be no serious effects in adult life," Gandy noted.
Efforts to develop a beta-secretase inhibitor have run into problems anyway, he said. "It's very difficult to get inhibitors that are fully active and nontoxic," he explained. One practical problem is to get a pill that is small enough to be swallowed.
Furthermore, drug development efforts aren't limited to enzymes, Gandy noted. The new finding doesn't affect programs for other anti-clumping approaches or for immunotherapy, Gandy said. But, he added, "we have to be doubly cautious now that this has emerged."
Another paper in the same issue of the journal described animal experiments on the formation of the beta-amyloid clumps. The studies showed that injecting the abnormal proteins collected from Alzheimer's patients caused Alzheimer-like protein clumps in the animals.
Alzheimer's disease thus resembles brain conditions such as mad cow disease that are caused by prions, molecules which cause abnormal folding of proteins, said Lary C. Walker, a research professor in neurology at Emory University and a member of the research team.
The experiments in which abnormal beta-amyloid protein from the brains of Alzheimer's disease patients were injected into mice are part of an effort "to take our understanding of what causes the disease as far back as possible," Walker said.
The work, most of which was done at the University of Tubingen in Germany, might eventually have an application in treatment of the condition, he said. "If we can learn how the seeding process initiates these changes, we can think about different therapeutic possibilities," Walker said.
The formation of beta-amyloid protein clumps in the brain is a basic feature of Alzheimer's disease, he noted. "We have no idea now how these proteins are corrupted," Walker said. "That is what this animal model will be useful for."
More information
The latest on Alzheimer's research is available from the Alzheimer's Association.
