Newly Discovered Inflammation Inhibitor Has Potential in Alzheimer’s Disease
A collaboration between scientists from Dublin’s Trinity College (Ireland) and the University of Queensland (Australia) identified a compound able to inhibit an inflammatory process common to many diseases, including Alzheimer’s disease. The study entitled “A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases” was published on line in the journal Nature Medicine.
Pathogenesis of several diseases, including Alzheimer’s, have a strong inflammatory component. Inflammatory processes can be triggered by molecules of the NOD-like receptor (NLR) family such as NLRP3. Once activated, this molecule leads to a cascade of events known as the NLRP3 inflammasome that ultimately causes the production of inflammatory factors. Aberrant activation of NLRP3 is responsible for increased inflammatory responses in complex diseases such as multiple sclerosis, Muckle-Wells syndrome, type 2 diabetes, Alzheimer’s disease and atherosclerosis.
Targeting this molecule can overcome the side effects of other anti-inflammatory drugs commonly used: “Drugs like aspirin or steroids can work in several diseases, but can have side effects or be ineffective. What we have found is a potentially transformative medicine, which targets what appears to be the common disease-causing process in a myriad of inflammatory diseases,” said Luke A J O’Neill, one of the team leaders.
Previous studies identified NLRP3 inhibitors, though neither very potent nor specific. This research team now identified a specific inhibitor of NLRP3 inflammasome, the molecule MCC950. They observed that it inhibits NLRP3 in mouse models of multiple sclerosis with consequent attenuation of disease progression. MCC950 also blocks production of inflammatory factors in blood samples from patients with a severe inflammatory disorder, Muckle-Wells syndrome. These results demonstrated the pharmaceutical potential of this specific NLRP3 inhibitor.
“MCC950 is blocking what was suspected to be a key process in inflammation. There is huge interest in NLRP3 both among medical researchers and pharmaceutical companies and we feel our work makes a significant contribution to the efforts to find new medicines to limit it,” said Rebecca Coll, the paper’s first author.
The researchers were able to demonstrate the potential of MCC950 in multiple sclerosis, an inflammatory disease of the central nervous system (CNS). However, the target for MCC950 is strongly implicated in other diseases of the CNS such as Alzheimer’s and Parkinson’s diseases indicating that it has the potential to treat all of these conditions. The fact that MCC950 can be orally administered further enhances the potential of this molecule as a therapeutic drug.
“MCC950 is able to be given orally and will be cheaper to produce than current protein-based treatments, which are given daily, weekly, or monthly by injection. Importantly, it will also have a shorter duration in the body, allowing clinicians to stop the anti-inflammatory action of the drug if the patient ever needed to switch their immune response back to 100% in order to clear an infection.” said Matt Cooper, chemist and also co-senior author in this study.
