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Compound May Prevent Painful Sickle Cell Crises

Aptamer prevents the traffic jam of cells that causes debilitating pain crises and associated mortality in sickle cell disease.

A new compound appears to prevent the traffic jam of cells that causes debilitating pain crises and associated mortality in sickle cell disease, researchers from the Medical College of Georgia report.

The aptamer, developed by Archemix Corporation in Cambridge, Mass., appears to work by occupying sticky receptors lining the walls of small blood vessels where sickle-shaped red blood cells and white blood cells can pile up, according to the study published in Blood. The cell traffic jam occludes blood and oxygen flow, causing pain, organ damage and, eventually, death.

"Many people are focusing on developing new therapies for sickle cell disease because right now, there is only one FDA-approved choice (hydroxyurea, a chemotherapeutic agent)," Dr. Diana R. Gutsaeva, MCG physiologist and molecular biologist and the study's first author, said in a press release. "We think this aptamer has potential to be one of those new therapies."

Patients can become resistant to hydroxyurea, which was approved in1998 as the first treatment for adults with sickle cell disease.

In a mouse with sickle cell disease, administering the aptamer prior to a pain crisis-provoking stressor reduced adhesion of sickle red blood cells by 90 percent and white blood cells by 80 percent, the researchers report. The animals also had increased blood flow velocity and reduced mortality.

MCG researchers believe the drug can now move to clinical trials where it has potential for treating an acute pain crisis - now primarily treated with narcotics - as well as avoiding one, if a tablet form becomes available. The current liquid form must been given intravenously or injected under the skin.

The Food and Drug Administration already has approved one aptamer to treat macular degeneration and others are under study for cardiovascular disease and blood disorders. MCG also is exploring the potential of inhaled nitric oxide in treating a sickle cell pain crisis. Results of a small clinical study, led by Dr. C. Alvin Head, Chairman of the MCG Department of Anesthesiology, and published in October 2010 in the American Journal of Hematology, showed that inhaling nitric oxide provides better pain control than standard self-administered morphine.

The new aptamer targets P-selectin receptors, which are highly expressed in sickle cell patients. "The aptamer locks them up so they do not function," Dr. Tohru Ikuta, MCG molecular hematologist and a study co-author, said. "There are almost no good compounds that inhibit cell adhesion and many that do are toxic." At least in their animal studies, the new compound wasn't toxic and didn't provoke an immune response, Ikuta said.

The research was funded by Archemix Corp., Southeastern Clinical and Translational Research Institute and the National Institutes of Health.

Source: Medical College of Georgia


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