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Discovery Promises Simpler Therapy for Sickle Cell Disease

rocess nitric oxide in the blood correspond to the severity of their disease symptoms. That result might explain a long-standing puzzle: patients with sickle cell exhibit extreme variability in the severity of their symptoms, despite the fact that the disease stems from a single genetic defect, Stamler said.

"This finding, if verified in clinical trials, could change physicians' approach to sickle cell disease," Stamler said. "Current efforts for managing the disease completely miss the role that red blood cell-derived nitric oxide plays. The disease might therefore be treated by more simple and effective methods than those now available to patients through the delivery of nitric oxide to blood cells."

The finding marks the first time that a defect in the ability of patients' red blood cells to process nitric oxide has been linked to a disease, the researchers said. The findings also raise the possibility that defective nitric oxide processing by red blood cells may represent a new class of blood diseases.

Patients with sickle cell disease have an abnormal form of hemoglobin. In the late 1990s, Stamler's team discovered that, in addition to its role in oxygen delivery, hemoglobin acts a biosensor, adjusting blood flow according to the oxygen demand of tissues and organs, by distributing nitric oxide.

Reports by the team in 2001 and 2002 further detailed nitric oxide's role in the red blood cell membrane, confirming it as the third major blood gas, along with oxygen and carbon dioxide. Those findings suggested that nitric oxide defects might play a role in the cardiovascular side effects of many disorders, including diabetes, heart attacks, septic shock and sickle cell disease.

In the current study, the researchers found that hemoglobin in the red cells of patients with sickle cell disease fails to process nitric oxide properly. As a result, they reported, the membranes of sickle red blood cells are deficient for the form of ni
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Source:DukeMedNews


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