MCC950 and NLRP3 Inflammasome Inhibition for Neurodegenerative Diseases

MCC950, an NLRP3 inflammasome inhibitor, was shown to reverse symptoms in two Parkinson's disease mouse models and was reported to have no toxicity issues. The only reason given in the following article for not pursuing clinical trials is that it is off-patent: https://www.genengnews.com/news/parkinsons-disease-drug-that-cools-brains-on-fire-could-enter-human-trials-in-2020/  

Given its mechanism of action it could be broadly effective against neurodegenerative diseases and even spinal cord injury ( https://www.frontiersin.org/articles/10.3389/fmolb.2020.00037/full ). 

Infections due to immunosuppression may be a problem, but there are reasons to think that MCC950 would be safer than immunosuppressive agents currently used to treat inflammatory conditions:  

"Thus, specific targeting of NLRP3 will not result in the complete blockade of IL-1β during infection and antimicrobial responses may remain intact. MCC950 may therefore have less immunosuppressive effects when compared to biologics such as Canakinumab, which has been shown clinically to increase the risk of these serious infections. MCC950 will also have a shorter half-life compared to the biologics Canakinumab and Rilonacept, and can therefore be withdrawn should unwanted effects occur such as infections." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392179/

[Update 2022-04-6]

An article in The Scientist states that MCC950 caused an elevation in liver enzymes in early human trials;  derivatives are under development for a wide range of conditions.


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