Olatec Therapeutics’ Lead Compound, Dapansutrile, a Selective NLRP3 Inhibitor, Prevents the Inflammatory Response and Restores Cognitive and Behavioral Deficits in a Mouse Model of Alzheimer’s Disease
- Category: Small Molecules
- Published on Tuesday, 29 December 2020 17:33
- Hits: 1048
- The data are published in the Proceedings of the National Academy of Sciences
- Results suggest a potential therapeutic benefit for dapansutrile in patients with neuroinflammatory diseases, e.g., Alzheimer’s Disease
- Preclinical results encourage clinical research with dapansutrile in Alzheimer’s Disease to investigate therapeutic effect in humans
NEW YORK, NY, USA I December 29, 2020 I Olatec Therapeutics LLC (“Olatec”) today announced the publication of data demonstrating the benefits of its selective NLRP3 inhibitor, dapansutrile, in a mouse model of Alzheimer’s Disease (AD). The data are published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS). The study shows 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 Disease (AD). 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 Niklas Lonnemann PhD, collaborated with Charles A. Dinarello MD, Olatec’s Scientific Advisory Board Chairman, among others in the study.
There has been growing evidence that neuroinflammation can have negative effects on the structural integrity of the brain and learning behavior. Specifically, the deposition of amyloid-β peptide can induce activation of the NLRP3 inflammasome and the over-production of pro-inflammatory cytokine Interleukin-1β (a central component of the body’s immune system), leading to a vicious cycle of cerebral neuroinflammation and debilitating cognitive impairment that progresses to AD.
The results of this study convincingly advocate for the therapeutic potential of oral treatment of neuroinflammatory diseases with an inhibitor of the NLRP3 inflammasome. Prof. Dr. Korte said, "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. We are hopeful that dapansutrile’s results can translate to humans and support our development of dapansutrile as an oral therapeutic in neurodegenerative diseases."
About Alzheimer’s Disease and its Significant Unmet Medical Need
Alzheimer’s disease is a progressive neurological disorder resulting in memory loss, behavioral symptoms, and loss of ability to perform daily activities. In advanced stages of dementia, AD can ultimately be fatal. As reported by the WHO, approximately 50 million people suffer from AD, which consumes an enormous medical and emotional price on society, families and caregivers. In 2015, the total global societal cost of dementia was estimated to be US$ 818 billion, equivalent to 1.1% of global gross domestic product (GDP). By mid-century, the number of Americans age 65 and older with Alzheimer’s dementia may grow to 152 million.
About Prof. Dr. Martin Korte
Prof. Dr. Martin Korte is a Neurobiologist and Director at the Institute of Zoology at TU Braunschweig. In 2012, he established and became head of the "Neuroinflammation and Neurodegeneration" research group at the Helmholtz Centre for Infection Research (HZI) to connect his experience in the fields of cellular neurobiology and neurophysiology with the areas of infection and neurodegenerative diseases. Specifically, Korte’s research focuses on cellular mechanisms of learning and memory, as well as memory loss. He is a member of the German academy, Berlin-Brandenburgische Academy of Sciences (BBAW), and is one of the most cited German neuroscientists. For his achievement in the public understanding of science, he was awarded with the Karl-Heinz-Beckurts prize and he was a founding member of the national Junge Akademie (Young Academy).
Dapansutrile (lab code: OLT1177®) is an investigational small molecule, new chemical entity that specifically binds to and blocks NLRP3 (nucleotide-binding and oligomerization domain [NOD]-, leucine rich repeat-, pyrin domain-containing 3), the sensor molecule integral in the formation of the NLRP3 inflammasome. Inflammasomes are multiprotein complexes involved in intracellular surveillance of danger signals that trigger an intense inflammatory response, via generation of bioactive IL-1β and IL-18 through caspase-1 activation. Dapansutrile has been shown to prevent the formation of the NLRP3 inflammasome, which in turn inhibits the production of IL-1β and IL-18. NLRP3 is one of the most characterized inflammasome sensors due to its involvement in a wide range of disorders, including sterile inflammation, infections, and rare genetic autoimmune syndromes. Dapansutrile is in Phase 2 clinical development and has been well tolerated and shown to improve clinical outcomes in patients with acute gout flare (see The Lancet Rheumatology) and heart failure (see Journal of Cardiovascular Pharmacology). Dapansutrile has also 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 (AMI), contact dermatitis, multiple sclerosis, melanoma and breast cancers, spinal cord injury (SCI) and Alzheimer’s disease.
About Olatec Therapeutics LLC
Olatec is a privately held, clinical-stage biopharmaceutical company developing a platform of oral NLRP3 inhibitors to treat and prevent a broad spectrum of acute and chronic inflammatory diseases known to be mediated by IL-1. In addition to the lead compound, dapansutrile, Olatec’s platform of proprietary compounds includes approximately 60 analogues (OLT Analogues) being screened as viable drug candidates. An IP portfolio protecting Olatec’s compounds consists of over 115 patents granted, covering dapansutrile and OLT Analogues. Olatec’s drug development team is comprised of experienced management and international experts in translational medicine with unparalleled expertise in inflammation and immunology and has been involved in the discovery and development of first-line inflammation treatments in the market today. For more information, please visit http://www.olatec.com.
SOURCE: Olatec Therapeutics