Successful Phase I trial of VU319 offers new hope for Alzheimer’s and schizophrenia, showcasing a breakthrough in drug discovery from basic research to clinical impact.
Discovery of VU0467319: an M1 Positive Allosteric Modulator Candidate That Advanced into Clinical Trials
Go to source). “This milestone highlights Vanderbilt’s ability to drive discovery from research to clinical impact,” said Provost and Vice Chancellor for Academic Affairs Cybele Raver. “The success of VU319 exemplifies how collaboration and innovation can bring real hope to patients and families facing Alzheimer’s and other neurodegenerative diseases.”
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‘Did You Know?
Worldwide, at least 55 million people are believed to be living with Alzheimer's disease or other dementias. If breakthroughs are not discovered, rates could exceed 152 million by 2050. #medindia #alzheimer #dementia’
Worldwide, at least 55 million people are believed to be living with Alzheimer's disease or other dementias. If breakthroughs are not discovered, rates could exceed 152 million by 2050. #medindia #alzheimer #dementia’
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A Transformative Step in Alzheimer's Drug Development
John Kuriyan, dean of basic sciences and University Distinguished Professor of Biochemistry and Chemistry, agreed, adding, “The successful phase I trial of VU319 marks a potentially transformative step in drug development for Alzheimer’s, showcasing Vanderbilt’s capacity to translate fundamental research into therapeutic discovery that brings the hope of real clinical impact.”VU319 is the first Vanderbilt end-to-end drug discovery effort, starting from the earliest basic science research through human clinical trials. The effort spanned a high-throughput screening hit-to-candidate selection to completion of a clinical trial.
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A Decade-Long Journey to Discover VU319
“After more than a decade of basic and translational research, the WCNDD was finally able to disclose how VU319, a unique M1 PAM, was discovered and profiled,” said Craig Lindsley, executive director of the WCNDD and University Professor of Pharmacology, Biochemistry and Chemistry who holds the William K. Warren, Jr. Chair in Medicine.Advertisement
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VU319’s Potential for Alzheimer’s, Schizophrenia, and More
In addition to treating Alzheimer’s disease, which affects roughly 6.9 million people over age 65 and has no known cure, VU319 has shown potential to treat memory loss in schizophrenia, prion diseases, Rett syndrome, vascular dementia, and Lewey body dementia.“Funding from the National Institute of Mental Health allowed the WCNDD to discover and develop VU319. An important philanthropic gift from the William K. Warren Foundation then enabled us to partner with DavosPharma to conduct critical early-stage studies and earn approval from the FDA as an investigational new drug, paving the way for the Alzheimer’s Association award to Dr. Paul Newhouse for the phase I trial,” Lindsley said. “Overall, it has been incredibly rewarding to drive a program from the most basic discovery stage and translate it into human clinical testing, all at Vanderbilt.”
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How VU319 Enhances Acetylcholine Activity
The neurotransmitter acetylcholine is responsible for learning and memory, but in Alzheimer’s and other neurodegenerative diseases, such as schizophrenia, it is one of the first that stops working and disables neurons from functioning properly. VU319, an M1 positive allosteric modulator, increases the efficacy of the endogenous neurotransmitter acetylcholine at the M1 receptor, acting as a dimmer switch to “turn-up”the gain on the receptor selectively, providing the best possible therapeutic index.Promising Results from Human Trial of VU319
In the human trial performed at Vanderbilt by Dr. Paul Newhouse, professor of psychiatry and pharmacology, director of the Vanderbilt Center for Cognitive Medicine, and clinical core director of the Vanderbilt Memory and Alzheimer's Center, the researchers saw signs of target engagement at the highest dose of the treatment that was tested and saw no side effects typical of other drugs working on the same area of the brain.The article, “Discovery of VU0467319: an M1 Positive Allosteric Modulator Candidate That Advanced into Clinical Trials,” was published in ACS Chemical Neuroscience. Following this successful phase I SAD clinical trial, the WCNDD is continuing to develop additional back-up M1 PAMs to enter into human clinical testing.
Translating Research into Drugs for Brain Disorders
The WCNDD extends traditional academic pursuits in basic science to take the most exciting advances in our understanding of human disease and drug targets to a point where these breakthroughs can directly impact patient care. Established with a $20-million gift from The William K. Warren Foundation in Tulsa, Oklahoma, the WCNDD houses approximately 100 renowned scientists with a diverse set of interests and skills working to translate research ideas into viable new drugs that prevent or treat serious brain disorders, such as Alzheimer’s disease, schizophrenia, and Parkinson’s disease.The Warren Foundation has been a longstanding supporter of Vanderbilt and its research efforts. Seven endowed faculty chairs currently are supported by the foundation.
“Supporting novel, research-based methods to combat devastating cognitive impairments and mental illnesses lies at the heart of our foundation’s mission,” said John-Kelly Warren, CEO of the Warren Foundation and grandson of the founders, in 2020. “It is also gratifying to support this research at Vanderbilt University, an institution that has made a significant impact on the lives of so many, including my family.”
Reference:
- Discovery of VU0467319: an M1 Positive Allosteric Modulator Candidate That Advanced into Clinical Trials - (https://pubs.acs.org/doi/10.1021/acschemneuro.4c00769#)
Source-Eurekalert
