Vanderbilt researchers reach milestone in Alzheimer's drug development

Vanderbilt researchers reach milestone in Alzheimer's drug development

Researchers at the Warren Center for Neuroscience Drug Discovery, a biotech in the Vanderbilt University School of Medicine Basics Sciences, have detailed the successful discovery of a Phase I clinical dose trial of VU319, a drug for memory loss in people with Alzheimer's disease and schizophrenia.

This milestone demonstrates Vanderbilt's ability to advance discovery from research to clinical impact. The success of VU319 illustrates how collaboration and innovation can bring real hope to patients and families living with Alzheimer's and other neurodegenerative diseases. “

Cybele Raver, Provost and Vice Chancellor for Academic Affairs

John Kuriyan, dean of undergraduate 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 disease, demonstrating Vanderbilt's ability to translate fundamental research into therapeutic discovery Detection from Vanderbilt to transfer basic research into therapeutic detection, this detection from Vanderbilt to transfer therapy, this detection from Vanderbilt brings the hope of real clinical impact. “

VU319 is Vanderbilt's first end-to-end drug discovery effort, starting from the earliest basic research in human clinical trials. The effort included high-throughput screening hit-to-candidate selection to complete a clinical trial.

“After more than a decade of fundamental and translational research, the WCNDD was able to finally reveal how VU319, a unique M1 Pam, was discovered and profiled” Chemistry, which holds the chair of William K. Warren Jr. in Medicine.

In addition to treating Alzheimer's disease, which affects approximately 6.9 million people over the age of 65 and has no proven cure, VU319 has shown potential for treating memory loss in schizophrenia, prion diseases, Rett syndrome, vascular dementia and Lewey body dementia.

"Funding from the National Institute of Mental Health enabled WCNDD to discover and develop VU319. A major philanthropic gift from the William K. Warren Foundation enabled us to work with Davospharma to conduct critical early-stage studies and receive approval from the FDA as a new drug that paves 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 take a program from the most basic discovery phase and translate it into human clinical testing at Vanderbilt."

The neurotransmitter -Acetylcholine is responsible for learning and memory, in Alzheimer's and other neurodegenerative diseases such as schizophrenia it is one of the first to stop working and neurons not functioning properly. VU319, a positive allosteric M1 modulator, increases the effectiveness of the endogenous neurotransmitter acetylcholine at the M1 receptor and acts as a dimmer switch to selectively “toggle” the receptor's gain, providing the best therapeutic index possible.

In that of 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 Center at Vanderbilt, the researchers found the highest dose of treatment tested was not typical of other drugs that target the same area of ​​the brain worked.

The article “Discovery of VU0467319: An M1 positive allosteric modulator candidate that entered clinical trials” was published in “ACS Chemical NeuroscienceOn December 11th. Following this successful Phase I SAD clinical trial, WCNDD continues to develop additional back-up M1 PAMs to conduct clinical testing.

The WCNDD expands traditional academic pursuits in basic science to address the most exciting advances in our understanding of human diseases and drug targets to the point where these breakthroughs can directly impact patient care. The William K. Warren Foundation in Tulsa, Oklahoma, established with a $20 million gift, the WCNDD is home to approximately 100 renowned scientists with diverse interests and skills, such as Alzheimer's disease, schizophrenia and Parkinson's disease.

The Warren Foundation has been a long-time supporter of Vanderbilt and its research efforts. Seven equipped faculty chairs are currently supported by the foundation.

“Bringing novel, research-based methods to combat devastating cognitive impairment and mental illness 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. “Delighted to support this research at Vanderbilt University, an institution that has a significant impact on the lives of so many, including my family has. "

Employees

WCNDD co-authors on this study include Michael S. Poslunsey, Michael R. Wood, Changho Han, Shaun R. Stauffer, Joseph D. Panarese, Bruce J. Melancon, Julie L. Engers, Jonathan W. Dickerson, Weimin Peng, Meredith J. Noetzel, Hyekyung P. Cho, Alice L. Rodriguez, Corey R. Hopkins, Ryan Morrison, Rachel D. Crouch, Thomas M. Bridges, Anna L. Blobaum, Olivier Boutaud, J. Scott Daniels, Jerri M. Colleen M. Niswender, Carrie K. Jones and P. Jeffrey Conn.

Davospharma employees include Michael J. Katates and Arlindo Castelhano, who conducted the new drug discovery studies, process chemistry, drug products and regulatory work.

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