Scientists Win $2 Million to Identify Potential New Treatments for Schizophrenia and Depression

By Eric Sauter

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have been awarded $2 million by the National Institute of Mental Health of the National Institutes of Health to develop new screening strategies to identify novel compounds with the potential to treat a number of neuropsychiatric disorders including schizophrenia, depression and drug dependence.

TSRI Associate Scientific Directors Patricia McDonald and Thomas Bannister will be the principal investigators (PIs) of the new three-year collaborative grant.

The new study will focus on a G protein-coupled receptor (GPCR) GPR151, called an “orphan receptor” because there are no known natural activating molecules (“ligands”). GPCRs play key roles in many physiological functions; they act as conduits transmitting signals from outside the cell to the interior by coupling to many intracellular effectors including G proteins to produce robust, varied and specific cellular responses.

“Identifying natural and surrogate ligands of GPR151 is important for determining its biological function,” McDonald said. “The difficulty is trying to build a screen for a receptor whose natural ligand and signal pathways are unknown, which is why our lab has developed a novel cell-based assay [test] that will allow us to screen GPR151 against the Scripps Drug Discovery Library.”

GPR151 has a distinctive pattern of distribution in mammalian brains, specifically in a small structure known as the habenula complex, which is located near the pineal gland in the midbrain region. Research suggests that this part of the brain is involved in behavioral choices in response to pain, anxiety and even sleep.

Once identified, McDonald said these GPR151 modulators, in collaboration with the Bannister lab, will be optimized and used to investigate this receptor’s role in regulating the habenula complex and its impact on both normal physiological processes and disease conditions.

Identifying GPR151-modulating ligands, McDonald added, will help link it to specific disorders and possibly establish it as a candidate for new drug discovery efforts.

“There are over 100 orphan GPCRs in the human genome; if we’re successful with this orphan GPCR, we’ll be able to take the same approach to many others,” she said.

Highly desirable as drug targets, GPCRs currently account for about 30 to 40 percent of all prescription pharmaceuticals on the market.

The number of the grant is 1R01MH111116.

Send comments to: press[at]scripps.edu