August 15, 2016

Foundation’s support speeds search for new schizophrenia drugs at Vanderbilt

Research in the Vanderbilt Center for Neuroscience Drug Discovery (VCNDD) aimed at developing innovative new treatments for schizophrenia just received a powerful assist from The William K. Warren Foundation.

Research in the Vanderbilt Center for Neuroscience Drug Discovery (VCNDD) aimed at developing innovative new treatments for schizophrenia just received a powerful assist from The William K. Warren Foundation.

The Tulsa, Oklahoma-based foundation announced it will increase its support by another $1 million, as VCNDD’s game-changing schizophrenia program approaches the point at which candidate drugs will be selected for testing in clinical trials. Two previous awards from the foundation have totaled $7.25 million since 2014.

Craig Lindsley, Ph.D., VCNDD director of Medicinal Chemistry and William K. Warren Jr. Professor of Medicine, said the center’s goal is to develop fundamentally new treatments born of deep basic science, not only for schizophrenia, but for multiple neuropsychiatric disorders.

The foundation’s support is essential to move drug-like molecules from laboratory and animal studies to the point where an investigational new drug (IND) application to test them in humans can be filed with the U.S. Food and Drug Administration (FDA), he said.

“The partnership between the VCNDD and The William K. Warren Foundation has been amazing,” Lindsley said. The foundation “stepped in at several critical points to enable the continued advancement of innovative new medicines,” he said.

“We are so appreciative of the tremendous support that the foundation has provided to help us develop new treatments for serious mental illness,” said the center’s founding director, P. Jeffrey Conn, Ph.D., the Lee E. Limbird Professor of Pharmacology at Vanderbilt University School of Medicine.

“We simply could not meet the major challenges of advancing a new potential medicine to clinical studies without the generous support that they are providing,” Conn said.

VCNDD is a pioneer in the development of allosteric modulators, small molecules that selectively adjust the activity of receptors in the brain like the dimmer switch in an electrical circuit and without causing serious side effects.

In the case of schizophrenia, Vanderbilt researchers are developing “positive allosteric modulators,” or PAMS, that may be able to control unmet clusters of symptoms that make it difficult for patients to function successfully in society. The molecules act on a key muscarinic receptor that binds the neurotransmitter acetylcholine.

Current medications for schizophrenia keep at bay the hallucinations and delusions that are the hallmark of the illness, but do little to address other symptoms, including cognitive difficulties and a tendency to withdraw from others. Many patients also develop metabolic disorders and significant weight gain on the drugs.

Conn and Lindsley are leading the schizophrenia research effort with VCNDD colleagues Carrie Jones, Ph.D., Colleen Niswender, Ph.D., and Thomas Bridges, Ph.D.

“Considering it has been over 30 years since a new drug has been developed for schizophrenia, we are privileged and excited to partner again with some of the best pioneering talents in uncovering the mysteries behind mental illness, and Vanderbilt, which has allowed them a platform to succeed,” said John-Kelly Warren, CEO of The William K. Warren Foundation.

“The global costs and suffering due to mental illness are staggering,” Warren said, “and the United States is not escaping this burden.”

By one estimate, nearly 44 million Americans 18 and older had a mental illness in the past year. Approximately 2.6 million adults have schizophrenia, yet many refuse or otherwise do not receive the treatment they need.

“We believe that better treatments with fewer side effects can significantly increase patients’ willingness to receive treatment, thus also greatly improving their healthcare outcomes,” Warren said.

The William K. Warren Foundation was created in 1945 by Mr. and Mrs. William Kelly Warren to provide the finest possible medical care and make enduring contributions to medical research, particularly in nervous system diseases. The goal is to improve lives, reduce societal costs and relieve human suffering.