Jkj193741 posted an article over on Stockhouse "World-first pill may stop Parkinson’s" about the potential of the NLRP3 inflammasome inhibitor MCC950 for Parkinson's. JK was asking about potential for combo with apabetalone. Both apabetalone and NLRP3 inhibitors have anti-inflammatory effects; however, through very different mechanisms. So in combo, there could be an extremely robust suppression of several facets of the inflammatory cascade. This could be good or could be bad. While too much inflammation is bad, too robust of a stranglehold on inflammation could also be bad. That's what's so great about apabetalone. Apabetalone seems to bring over-active inflammation back down to a basal state (in addition to its other effects on vascular calcification, apo-AI/HDL, complement, coagulation, and glucose metabolism) without completing shutting it off. 

Here is a great article entitled "NLRP3 inhibitors stoke anti-inflammatory ambitions" on the recent progress by pharma to develop inhibitors of NLRP3, including the history and potential for MCC950.

NLRP3 is a very exciting drug target and there is a ton of potential here for NLRP3 inhibitors. Still early going for clinical development of this drug class. As far as I can tell, MCC950 is the only NLRP3 inhibitor to make it to the Phase 2 stage but was not developed further presumably because of hepatic toxicity. So many years to go for NLRP3 inhibitors to prove themselves in the clinic for safety and efficacy.

A couple good NLRP3 reviews below, though I don't know if they are open access. 

Targeting the NLRP3 inflammasome in inflammatory diseases

https://www.ncbi.nlm.nih.gov/pubmed/30026524

The NLRP3 inflammasome: molecular activation and regulation to therapeutics

https://www.ncbi.nlm.nih.gov/pubmed/31036962

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