A Novel Molecular Target for Seizure Therapy and Neuroprotection

UAB Research Foundation
posted on 11/08/2011

Epilepsy affects approximately 2.5 million people in the United States, and results in an estimated annual cost of $15.5 billion in healthcare. It is estimated that one-third of epileptics are unresponsive to current pharmacological therapies, and therefore there exists an urgent need for better treatments. Researchers at the University of Alabama at Birmingham (UAB) have identified a novel molecular target, RGS4, a molecule regulating G-protein signaling, that enhances neuroprotection. This discovery makes possible the development of new therapies for epileptics and people with neural damage including brain injury and stroke.

Suggested Uses

Neurology

Advantages

Therapeutics designed against this target:

would cause seizure suppression, and prevent neuronal damage and recurrent spontaneous seizures

would have fewer side-effects than current anti-epileptic therapeutics which target sodium/calcium channels and GABAergic transmission, and

would also be beneficial for neuropathic pain because the mechanism modulates adenosine’s protective effect against neuroinflammation.

Innovation Details

Detailed Description

In the central nervous system, adenosine is an endogenous neuromodulator released to protect neurons from damage. Adenosine exerts its protective effects through the A1 subtype adenosine receptor (A1R), a member of the G protein-coupled receptor superfamily. A1R is negatively regulated by RGS4, a regulator of G-protein signaling, and is in a complex with neurabin, a neural-specific scaffold protein. Together this complex negatively regulates adenosine signaling through A1R. Molecules designed to block RGS4 will promote the neuroprotective effects of endogenous adenosine while avoiding side effects associated with exogenous ligands. Researchers at UAB have validated this target with a known inhibitor of RGS4, CCG-4986. Blocking this target in vivo results in a reduction in seizure severity/duration and prevention of neuronal death and mortality in a mouse seizure model. Targeted therapeutics that block the RGS4/neurabin/A1R signaling complex will therefore reduce seizure severity and duration, and promote neuroprotection.

File Number: U2010-0078

Web site: http://www.uab.edu/uabrf/search-technologies

Disease: Central Nervous System

Other Information:

MANAGING LICENSING ASSOCIATE

STACEY S. KELPKE, PH.D.

skelpke@uab.edu (205) 996-2538

IP PROTECTION

International Patent Application Serial No. PCT/US2012/057056, filed September 29, 2012.

PRINCIPAL INVESTIGATOR

Qin Wang, M.D., Ph.D., Department of Physiology and Biophysics, UAB.

IP Protection