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Vanderbilt University Breakthrough Drug Shows Promise for Alzheimer’s and Schizophrenia
Researchers at the Warren Center for Neuroscience Drug Discovery (WCNDD) at Vanderbilt University have announced a groundbreaking achievement: the successful completion of a Phase I clinical trial for VU319, a drug that could significantly impact the treatment of memory loss in individuals with Alzheimer’s disease and schizophrenia.
VU319, the first drug to emerge from Vanderbilt’s end-to-end drug discovery process, has advanced from basic science research to human clinical trials, marking a major milestone in the fight against neurodegenerative diseases. The clinical trial, which tested a single ascending dose (SAD) of the drug, demonstrated positive results, including clear evidence of target engagement at the highest dose, without the side effects commonly seen with similar treatments.
“This milestone highlights Vanderbilt’s ability to drive discovery from research to clinical impact,” said Cybele Raver, Provost and Vice Chancellor for Academic Affairs at Vanderbilt University. “The success of VU319 exemplifies how collaboration and innovation can bring real hope to patients and families facing Alzheimer’s and other neurodegenerative diseases.”
The research, detailed in the article “Discovery of VU0467319: an M1 Positive Allosteric Modulator Candidate That Advanced into Clinical Trials” published in ACS Chemical Neuroscience, marks a potentially transformative step in drug development for Alzheimer’s disease. John Kuriyan, Dean of Basic Sciences and University Distinguished Professor of Biochemistry and Chemistry at Vanderbilt, echoed the significance of the trial’s success, noting that it highlights the university’s capacity to translate fundamental research into therapeutic discoveries that have real clinical impact.
Craig Lindsley, Executive Director of the WCNDD, emphasized the drug’s potential, stating, “After more than a decade of basic and translational research, we’re excited to disclose how VU319, a unique M1 positive allosteric modulator (PAM), was discovered and profiled.”
The drug’s unique mechanism of action targets the M1 receptor, a key component of the brain’s acetylcholine system, which plays a critical role in learning and memory. In Alzheimer’s and schizophrenia, the acetylcholine system is often one of the first to fail, contributing to cognitive decline. VU319 works by increasing the efficacy of acetylcholine at the M1 receptor, offering a novel approach to restoring function in these areas of the brain. This “dimmer switch” effect selectively amplifies receptor activity, providing a promising therapeutic benefit without overstimulation.
The Phase I trial, led by Dr. Paul Newhouse, Professor of Psychiatry and Pharmacology, and Director of the Vanderbilt Center for Cognitive Medicine, showed no adverse effects typical of other treatments targeting the same brain regions. This success paves the way for future clinical trials of VU319 in larger patient populations.
In addition to its potential for Alzheimer’s disease, which currently affects approximately 6.9 million people over the age of 65 in the United States alone, VU319 also holds promise for treating memory loss in schizophrenia, prion diseases, Rett syndrome, vascular dementia, and Lewy body dementia.
With the successful Phase I trial behind them, the WCNDD is now focused on advancing additional M1 PAMs into human clinical testing, continuing to develop treatments that could transform the lives of individuals with neurodegenerative diseases.
For more information, the full study can be found in ACS Chemical Neuroscience (2024), DOI: 10.1021/acschemneuro.4c00769.
