Targeting inflammation restores memory in Alzheimer’s mice

Posted on 11th August 2016

Nature Communications: Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer’s disease in rodent models

Researchers at the University of Manchester have shown that a common anti-inflammatory drug may be able to rescue memory problems in mice with features of Alzheimer’s disease. The drug, called mefenamic acid, was also shown to halt brain inflammation in the disease according to a study published today in the journal Nature Communications.

Inflammation is the body’s defense mechanism, a biological process that activates in response to damage or infection. While usually beneficial, we know that inflammation also plays a role in diseases like Alzheimer’s where it may actually contribute to damage to cells in the brain. A protein called NLRP3 can trigger the formation of a complex of inflammatory proteins called the ‘NLRP3 inflammasome’ and research has shown that this complex is activated in Alzheimer’s. A drug that could target this protein could potentially prevent some of the damage caused by inflammation in the disease.

Researchers in this study set out to investigate whether any existing anti-inflammatory drugs could be used to block the inflammatory activity of the NLRP3 inflammasome complex. Working with cells in the laboratory, the team found that a group of anti-inflammatory drugs called fenamates seemed to block the downstream effect of NLPR3 whereas others, like ibuprofen, did not.

Taking this finding forward, the researchers investigated the effect of a fenamate called mefenamic acid on rats that were injected with the hallmark Alzheimer’s protein, amyloid. The treatment seemed to prevent the rats from developing memory problems that would usually be brought on by amyloid. The team then investigated the drug in mice bred to develop features of Alzheimer’s as they age. They treated the mice with mefenamic acid at a point when memory problems had started to show. Mice that were treated over a period of 28 days showed no evidence of memory problems compared to untreated mice, and there were no indications of inflammation when their brains were examined.

Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK said:

“There is increasing evidence of a key role for the immune system in Alzheimer’s, making it an attractive target for the development of new treatments for the disease. This research in mice suggests that an existing anti-inflammatory drug could have an effect on an important Alzheimer’s disease process. This finding is promising and will need following up to explore in more detail whether this class of drug could hold potential as a treatment for Alzheimer’s. Studying the effect of drugs for Alzheimer’s in mice is an important step that can provide valuable insights. However, carefully controlled clinical trials are vital for establishing the safety and efficacy of any treatment in people.

“Research like this is crucial as there are currently no treatments that can alter the progression of Alzheimer’s in the brain or protect nerve cells from damage in the disease. Drugs that act against the immune system have real potential to limit damage in Alzheimer’s and Alzheimer’s Research UK is investing heavily in this approach through our drug discovery initiatives. We desperately need to see greater investment in research if we are to find new ways to help the tens of thousands of people who develop Alzheimer’s in this country every year.”

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