NEW YORK—Olatec Therapeutics LLC has reported the publication of data demonstrating the benefits of its selective NLRP3 inhibitor, dapansutrile, in a mouse model of Alzheimer’s disease (AD). The data have been published in Proceedings of the National Academy of Sciences.
The study shows that oral dosing with dapansutrile inhibits pathophysiological inflammatory processes, recovers significant cognitive losses, and prevents neuroinflammation in the brains of transgenic mice induced with Alzheimer’s. The results point to the therapeutic potential of oral treatment of neuroinflammatory diseases with an NLRP3 inhibitor.
Dapansutrile specifically binds to and blocks NLRP3, the sensor molecule integral in the formation of the NLRP3 inflammasome. It has been shown to prevent the formation of the NLRP3 inflammasome, which in turn inhibits the production of interleukin (IL)-1β and IL-18.
Prof. Dr. Martin Korte, director of the Zoological Institute at the Technische Universität Braunschweig (TU Braunschweig) was the study’s principal investigator. His team from the TU Braunschweig, including Dr. Niklas Lonnemann, collaborated with Dr. Charles A. Dinarello, scientific advisory board chairman of Olatec, among others in the study.
There is growing evidence that neuroinflammation has negative effects on the structural integrity of the brain and learning behavior. The deposition of amyloid-β peptide can induce activation of the NLRP3 inflammasome and the overproduction of IL-1β, leading to a vicious cycle of cerebral neuroinflammation and debilitating cognitive impairment that progresses to Alzheimer’s.
“Our findings are another important piece of the puzzle in Alzheimer’s disease research. They support the knowledge that inflammatory reactions appear to play a more critical role in the development of AD than previously assumed. This was demonstrated by dapansutrile, which is shown to have positive effects in the mouse brain and can successfully inhibit the NLRP3 inflammasome,” noted Korte. “We are hopeful that dapansutrile’s results can translate to humans and support our development of dapansutrile as an oral therapeutic in neurodegenerative diseases.”
Dapansutrile is currently in Phase 2 clinical development; it has been well tolerated and shown to improve clinical outcomes in patients with acute gout flare and heart failure. Olatec also points out that dapansutrile has been observed to have anti-inflammatory properties and other promising activity in a broad spectrum of over 20 preclinical animal models, including arthritis, asthma, acute myocardial infarction, contact dermatitis, multiple sclerosis, melanoma and breast cancers, and spinal cord injury.