Researchers at the University of Illinois at Chicago have been awarded a three-year $2.1 million grant from the National Institute of Mental Health to develop a new drug to treat bipolar disorder.
The goal is to develop a compound that is able to enter the brain and block the mania associated with the disease, says principal investigator Alan Kozikowski, professor of medicinal chemistry and pharmacognosy.
"Currently, treatments for bipolar disorder include so-called 'mood stabilizers' -- lithium and valproic acid," Kozikowski said. "Both are relatively dated drugs that are only partially effective and produce various undesirable side effects, including weight gain."
Efforts to understand the molecular target for lithium have shown that compounds that inhibit the enzyme glycogen synthase kinase-3 may mimic the therapeutic action of the mood stabilizers, Kozikowski said, and might point the way to the design of improved drugs for treating patients with bipolar disorder.
More than 2 million American adults, or about 1 percent of the over-18 population, suffer from bipolar disorder, a mental illness that causes extreme mood swings. Also called manic-depression, it may be caused by a chemical imbalance in the brain.
A person who has bipolar disorder at times feels happy, full of energy and able to do anything. In this manic phase the person may not want to rest. At other times, the person feels sad and depressed, not wanting to do anything. People with bipolar disorder can quickly go from mania to depression and back again.
Safe, selective GSK-3 inhibitors are needed as both pharmacological tools and as therapeutics for application to a variety of central nervous system disorders, including several bipolar disorders, Parkinson's disease and Alzheimer's disease, Kozikowski said.
His group has already identified some potent GSK-3 inhibitors by screening analogs of staurosporine, a natural product that is able to block a number of protein kinases. Some of these compounds are able to protect nerve cells in the test-tube and block mania in animals, he said.
"Other members of this chemical series have recently been shown to potently inhibit the production of Abeta, a protein believed to be a causative factor in Alzheimer's disease," Kozikowski said. "We anticipate that further research efforts may well lead to compounds that can be advanced to the clinic."
Working with Kozikowski are Sylvie Blond, associate professor in UIC's Center for Pharmaceutical Biotechnology; Pavel Petukhov, assistant professor of medicinal chemistry and pharmacognosy; Irina Gaysin, senior research specialist of medicinal chemistry and pharmacognosy; and Paul McGonigle of PsychoGenics, Inc., of Tarrytown, N.Y.
For more information about UIC, visit www.uic.edu.