The University of Illinois at Chicago has been awarded a $4.6 million grant from the National Heart, Lung, and Blood Institute to study the molecular neurobiology of chronic pain in patients with sickle cell disease and to develop potential new drug treatments.
Characterized by irregularly shaped red blood cells, sickle cell disease is an inherited condition that affects approximately 100,000 Americans. The misshapen blood cells are less flexible than normal cells and do not pass through blood vessels easily, sometimes causing a blockage that slows or stops blood flow and prevents delivery of oxygen to nearby tissues and organs. Patients experience chronic pain, as well as episodes of acute pain that can result in hospitalization.
While there have been many advances in managing the disease and acute pain crises, researchers still do not know much about how and why patients experience chronic pain.
"Sickle cell patients are living longer and treatment has improved, but pain is still a major issue," said principal investigator Z. Jim Wang, professor of pharmacology and pharmaceutics in the UIC College of Pharmacy.
Wang and his colleagues have spent years studying pain, how it develops and how it's treated, including ways to fight the addictive nature of some painkillers, and have developed an array of cellular markers and tests that make it easier to study pain in sickle cell disease.
The new funding will provide an opportunity for Wang to refine these tools and develop new therapeutic leads for treating chronic pain in sickle cell disease.
One of the targets to be investigated is a class of protein kinases called PKCs. "We have studied each member of the PKC family and have identified three distinct isoforms of PKC that are likely involved in chronic pain," Wang said. "We need to understand more about how these molecules work and what happens when they are activated in chronic pain, and we need to look for new therapeutic drugs."
Wang says he hopes to identify various molecular mechanisms and explore ways to target one or more of these mechanisms for controlling pain in sickle cell disease. He says he is optimistic because the funding -- a seven-year, R35 Outstanding Investigator Award -- encourages "big ideas, not small conclusions."
"This type of funding is unique because it allows for a broad range of research ideas to be pursued simultaneously," Wang said. "This will help us incorporate newly developed technologies into our study designs, for example, and expand in new directions."
According to the National Institutes of Health, R35 awards are meant to provide long-term support to an experienced investigator with an outstanding record of research productivity and encourage long-term projects of unusual potential.
Co-investigator on the grant Dr. Robert Molokie says he hopes this research will fill a void in doctors' understanding of sickle cell disease and one day translate into improved quality of life for his patients.
"Dr. Wang's research on the basic science principles behind pain in sickle cell disease and our ability to take those findings to the clinic to improve our patients' lives is exciting," said Molokie, clinical associate professor of medicine in the UIC College of Medicine and the UI Health Sickle Cell Center.