Common NSAID reversed Alzheimer's memory loss in mice

Researchers have shown that an already-approved non-steroidal anti-inflammatory drug (NSAID) completely reversed memory loss and reduced inflammation of the brain in a mouse model of Alzheimer’s disease. They reported their results August 11, 2016 in Nature Communications.

“Our research shows for the first time that mefenamic acid, a simple non-steroidal anti-inflammatory drug, can target an important inflammatory pathway called the NLRP3 inflammasome, which damages brain cells,” said lead investigator David Brough, PhD, Senior Lecturer in Biology, Medicine and Health at the University of Manchester, in Manchester, UK.

“Until now, no drug has been available to target this pathway, so we are very excited by this result,” Dr. Brough added.

The NLRP3 inflammasome is an important contributor to inflammatory diseases, including Alzheimer’s, atherosclerosis, type 2 diabetes, and others. Also, amyloid beta, which is a causative factor in the development of Alzheimer’s disease, is a known activator of the NLRP3 inflammasome. As such, many researchers have been seeking a therapeutic inflammasome inhibitor.

For this study, Dr. Brough and colleagues tested mefenamic acid—an NSAID used to treat acute pain, particularly menstrual pain. The researchers gave the NSAID to a group of 10 transgenic mice with symptoms of Alzheimer’s disease, and gave a placebo to a similar group of mice.

After 18 days, the researchers evaluated memory in the mice using an object recognition test. Those in the placebo group performed far worse than those in the NSAID group.

After one month, the mice were euthanized and their brains examined. The brains of the mice in the placebo group showed substantial evidence of microglial activity in the subiculum, an indication of amyloid beta pathology.

But the brains of the mice given mefenamic acid showed that Alzheimer’s disease-related neuroinflammation had completely abated, and that levels of microglial activity and the proinflammatory cytokine interleukin-1b (IL-1b) had been reduced to that of wild-type mice.

In light of these promising results, “We are now preparing applications to perform early phase II trials to determine a proof-of-concept that the molecules have an effect on neuroinflammation in humans,” Dr. Brough said.

“Because this drug is already available and the toxicity and pharmacokinetics of the drug [are] known, the time for it to reach patients should, in theory, be shorter than if we were developing completely new drugs,” he added. “However, much more work needs to be done until we can say with certainty that it will tackle the disease in humans, as mouse models don’t always faithfully replicate the human disease.”

So, patients should not be prescribed mefenamic acid for Alzheimer’s disease just yet.