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Grant spurs schizophrenia research

Feb. 12, 2015, 9:26 AM

Vanderbilt University is partnering with the William K. Warren Foundation of Tulsa, Oklahoma, on research aimed at improving the treatment of schizophrenia and other forms of serious mental illness.

The foundation will provide $5 million to Vanderbilt over three years to develop a potential new drug class that may be more effective than current therapy and with fewer side effects. The project is led by Craig Lindsley, Ph.D., and Jeff Conn, Ph.D., leaders in Vanderbilt’s neuroscience drug discovery effort.

“This partnership comes at the ideal time,” said Lindsley, William K. Warren Jr. Professor of Medicine and director of medicinal chemistry in the Vanderbilt Center for Neuroscience Drug Discovery.

“It will support the last stages of preclinical testing of promising compounds required before testing in humans can begin, as well as optimization of back-up compounds for our most advanced drug candidates,” he said.

The program targets a class of neurotransmitter receptors, called G-protein-coupled receptors (GPCRs), with a novel mechanism of action by compounds called allosteric modulators. These compounds increase or decrease the activity of receptors in the brain, much like the dimmer switch in an electrical circuit.

Preclinical animal studies suggest that by modulating the activity of specific GPCR subtypes, these compounds may be able to selectively control multiple, unmet symptom clusters in schizophrenia and other brain disorders without causing serious side effects.

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.

Lindsley said the goal of the Vanderbilt effort is to offer patients a fundamentally new treatment, born out of deep basic science.

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

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