Researchers reported Wednesday common pain killers such as ibuprofen could dissolve the cell-strangling buildup of a brain protein that characterizes Alzheimer's disease, possibly thwarting progression of the mind-wasting disorder that exacts a hefty emotional and economic price.
Investigators at the University of California, Los Angeles, found some of the over-the-counter medications, known as non-steroidal anti-inflammatory drugs, might whittle away the deranging and deadly deposits of excess amyloid protein in the brain and prevent the formation of new ones.
The toxic plaques -- which stifle nerve cells' ability to communicate with each other, causing them to die -- are a definitive hallmark of Alzheimer's.
The neurodegenerative disease gradually robs its victims of their mental faculties, eventually leaving them wheelchair-bound and in need of constant care. The disorder, which sets in at an average age of 79, afflicts some 18 million people, a figure expected to nearly double to 34 million by 2025 as the world's population continues to grow older.
Using newly available technology, the scientists discovered a promising mechanism by which particular medicines might protect against the disease that affects 4.6 million Americans and takes a $100-billion bite out of the U.S. economy each year.
"Our work sheds new light as to why certain NSAIDs may work in delaying the progression of Alzheimer's disease," principal investigator Dr. Jorge Barrio, professor of molecular and medical pharmacology at UCLA's David Geffen School of Medicine, told United Press International.
Barrio and his team reached three major conclusions:
-- Common pain killers might slow the formation of and/or dissolve brain amyloid plaques associated with Alzheimer's disease;
-- This effect might explain previous observations of lower Alzheimer's risk among people who take anti-inflammatory medications;
-- The research is significant because it could lead to drug treatments for Alzheimer's and ways to interfere with the disease process while there still is time to minimize the damage -- before brain cell degeneration occurs and clinical symptoms appear.
The results are based on laboratory tests using a new chemical marker that allowed the researchers to watch the pain medications at work and measure their effect. The tool they designed, called FDDNP, highlighted the trouble spots with a fluorescent glow, painting a vivid picture of how the drugs attach to the menacing mounds of protein.
The deposits are key suspects in the cell disruption and death that lead to disorientation, progressive memory loss and other cognitive decline.
"It is too early to say that people should take these drugs to stave off future brain degeneration, but the findings are encouraging that in the near future, this line of inquiry may lead to practical preventive strategies," said study co-author Dr. Gary Small, Parlow-Solomon Professor on Aging, professor of psychiatry and biobehavioral sciences and director of UCLA's Center on Aging.
The possibility that agents already on store shelves might play a part in the care of treatment of the devastating disorder raises a newfound hope, noted Dr. James Galvin, assistant professor of neurology, director of the Memory Diagnostic Center and head of the Laboratories for Dementia Research at the Washington University School of Medicine in St. Louis.
"This is most important ... because of the cost and time lag required to develop and test new compounds and gain (Food and Drug Administration) approval, which can take upwards of 10 years," he told UPI.
Researchers cautioned against interpreting the findings as a green light for wholesale consumption of pain killers to forestall dementia.
"NSAIDs should only be taken if prescribed for arthritis or some other approved indication," Small told UPI, noting further studies are needed to determine the cause and effect of the results.
Before embarking on any prolonged drug regimen, people, particularly the elderly, should consider such potential side effects as stomach irritation, ulcers and even eventual kidney failure, as suffered by Miami Heat center Alonzo Mourning, San Antonio Spurs forward Sean Elliot and several other professional athletes, Galvin cautioned.
Also, they should keep in mind several NSAIDs tested as potential Alzheimer's treatments, including naproxen, Vioxx and Celebrex, showed no significant benefit and in fact might have contributed to adverse reactions, including stroke, in some participants, he advised.
Last, researchers pointed out, not all NSAIDs are created equal and where one might succeed, another could fail.
The results, which will be published in the March 31 issue of the journal Neuroscience, put a new spin on previous observations that link prolonged use of pain medicines and a reduced Alzheimer's risk, scientists said.
"The present study suggests that these drugs may work, not because they inhibit (the) inflammatory process, but because they actually get into the central amyloid core and prevent the protein from aggregating," Small told UPI.
The investigators discovered the drugs' attachment to the amyloid plaques when they added ibuprofen and naproxen to Alzheimer's-tainted brain fibers and tossed in the FDDNP marker to watch the effect. Follow-up test-tube studies indicated the medications can dissolve the plaques and even stop their formation.
"This new technology will likely help us monitor new vaccines and drugs designed to prevent and treat the brain damage caused by Alzheimer's disease," Small predicted.
The study extends previous findings that pointed to the potentially protective powers of NSAIDs against Alzheimer's. By identifying a specific site of the drugs' action, the new research could lead to designing agents aimed directly at interfering with the disease-promoting mechanisms, scientists said.
Next, the team will monitor therapies in a group of Alzheimer's patients, comparing the results with those in disease-free individuals and patients with other dementias.
"These studies suggest a previously unsuspected way in which the non-steroidal anti-inflammatory drugs may interact with Alzheimer amyloid," said Dr. John Breitner of the Veterans Administration Puget Sound Health Care System in Seattle and the University of Washington. "The UCLA work appears to open a whole new avenue of investigation in this important area."
