Grant Combats Sickle Cell Disease

Congratulations to Kenneth Ataga, M.D., and Nigel Mackman, Ph.D., who have received a 50K Planning Grant from the North Carolina Translational and Clinical Sciences (NC TraCS) Institute. They will use the funds to pursue a million-dollar U54 institutional award from the NIH, which should enable them to develop a novel treatment for patients with sickle cell disease.

Sickle cell disease is the most common inherited blood disorder in the United States, affecting 1 out of every 500 African Americans. In the disease, the body’s red blood cells assume an abnormal, rigid, sickle shape. These abnormally shaped cells can get stuck in small blood vessels and block blood flow and oxygen to parts of the body, causing episodes of excruciating pain and, eventually, permanent damage to critical organs.

Ataga, associate professor of medicine and director of the sickle cell program, and Mackman, professor of medicine and director of the UNC McAllister Heart Institute, aren’t focusing on the sickle cells themselves. Instead, their studies target the blood coagulation cascade. This cascade is normally responsible for forming clots to stop bleeding from cuts or other injuries, but is abnormally active in people with sickle cell disease.

The researchers are betting that by blocking this abnormal clotting, they can interrupt the vicious cycle between coagulation and inflammation that exacerbates the symptoms of sickle cell disease. Their proposal consists of both basic and proof of concept trials with the two new oral anticoagulant drugs rivaroxaban and dabigatran.

Ataga and Mackman have assembled a team of basic and clinical scientists that in addition to themselves include Nigel Key, M.D., professor of medicine and director of the UNC Hemophilia and Thrombosis Center, and Rafal Pawlinski, Ph.D., assistant professor of medicine. Together, Ataga, Mackman, Key and Pawlinski will act as multiple PIs on the proposal. Funds from the planning grant will be used to strengthen their preliminary studies with a mouse model of sickle cell disease and design clinical trials in human patients, all before submitting U54 proposal on May 8, 2012.