The Anti-Inflammatory Approach to Treating Alzheimer's Disease

Inflammation in the brain contributes to the progression of Alzheimer's disease. This has been known for some time, but there has been surprisingly little progress in building anti-inflammatory treatments. Some years ago, one approach using existing anti-inflammatory drugs failed in clinical trials, for example. This might be explained by the fact that the immune cells of the brain are quite different from those of the rest of the body, and neuroinflammation is consequently different in its details when compared with inflammation in other tissues. Here, researchers are working on a similar approach that might have more success, but given the history to date optimism may be misplaced. Certainly moving towards rapid testing in humans for any results of this nature in mice that were obtained using existing drugs seems to be a sensible approach:

In the study transgenic mice that develop symptoms of Alzheimer's disease were used. One group of 10 mice was treated with mefenamic acid, a simple Non-Steroidal Anti Inflammatory Drug (NSAID), and 10 mice were treated in the same way with a placebo. The mice were treated at a time when they had developed memory problems and the drug was given to them by a mini-pump implanted under the skin for one month. Memory loss was completely reversed back to the levels seen in mice without the disease.

"There is experimental evidence now to strongly suggest that inflammation in the brain makes Alzheimer's disease worse. Our research shows for the first time that mefenamic acid can target an important inflammatory pathway called the NLRP3 inflammasome, which damages brain cells. Until now, no drug has been available to target this pathway, so we are very excited by this result. 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. Because this drug is already available and the toxicity and pharmacokinetics of the drug is known, the time for it to reach patients should, in theory, be shorter than if we were developing completely new drugs. 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."


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