Steve Paul, MD, Chief Scientific Officer & President of Research and Development at Karuna Therapeutics, gives the keynote presentation, "Muscarinic Antipsychotics: A Potential New Generation of Medicine for Treating Schizophrenia," at the Science & Innovation Symposium, sponsored by Rogers Behavioral Health, as part of One Mind's 29th Music Festival for Brain Health, held on September 9, 2023 at the Staglin Family Vineyard.
Watch all the 2023 Science & Innovation Symposium presentations here in the full playlist: • One Mind's 2023 Science & Innovation ...
Schizophrenia remains a challenging disease to treat effectively with current antipsychotic medications due to their limited efcacy across the entire spectrum of core symptoms as well as their often burdensome sideeffect proles and poor tolerability. An unmet need remains for novel, mechanistically unique, and better tolerated therapeutic agents for treating schizophrenia, especially those that treat not only positive symptoms but also the negative and cognitive symptoms of the disease. Almost 25 years ago, the muscarinic acetylcholine receptor (mAChR) agonist xanomeline was reported to reduce psychotic symptoms and improve cognition in patients with Alzheimer’s disease. The antipsychotic and procognitive properties of xanomeline were subsequently conrmed in a small study of acutely psychotic patients with chronic schizophrenia. These unexpected clinical ndings have prompted considerable efforts across academia and industry to target mAChRs as a new approach to potentially treat schizophrenia and other psychotic disorders. I will discuss recent advances in mAChR biology and pharmacology and the current understanding of the relative roles of the various mAChR subtypes, their downstream cellular effectors, and key neural circuits mediating the reduction in the core symptoms of schizophrenia in patients treated with xanomeline. I will also provide an update on the status of novel mAChR agonists currently in development for potential treatment of schizophrenia and other neuropsychiatric disorders.
STEVE PAUL BIO
Steve Paul is the Chief Scientific Officer, President of Research and Development, and a member of the board of directors at Karuna Therapeutics. He most recently served as Chairman of the Board, President, and Chief Executive Officer from 2018 – 2022. He is an expert in central nervous system (CNS) drug discovery and development. Dr. Paul spent 17 years at Eli Lilly and Company (NYSE: LLY), during which time he held several key leadership roles, including Executive Vice President for Science and Technology and President of the Lilly Research Laboratories. At Lilly he was responsible for the company’s overall research and development efforts and helped to oversee the development of CNS drugs such as Zyprexa® and Cymbalta® as well as the development of xanomeline where its antipsychotic and procognitive properties were initially demonstrated.
Prior to Lilly, Dr. Paul spent 18 years at the National Institute of Health (NIH) and served as the Scientific Director of the National Institute of Mental Health (NIMH). Dr. Paul is a cofounder and board member of Sage Therapeutics (NASDAQ: SAGE) and a cofounder of Voyager Therapeutics (NASDAQ: VYGR) where he served as President, Chief Executive Officer. Dr. Paul is the former director of the Appel Alzheimer’s Disease Research Institute at Weill Cornell Medical College and is currently a Professor of Psychiatry and Neurology at Washington University of St. Louis School of Medicine.
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