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Providing New Hope for Treating Sickle Cell Disease
CHORI Scientist Garners Highly Competitive Doris Duke Charitable Foundation Award

February, 2012 - Sickle cell disease (SCD), a genetic blood disorder affecting millions worldwide, is most known for the classic sickle shape of the red blood cells. Patients with SCD have a variety of complications, including what are known as vaso-occlusive crises, in which restricted blood flow causes episodes of extreme pain. Patients miss school, appointments, work, and often end up hospitalized until the pain subsides. While researchers have been working to identify certain biomarkers that might indicate when SCD patients are going to have pain crises, no treatments have yet been discovered to prevent or alleviate the vaso-occlusive crises when they strike.

CHORI Associate Scientist Carolyn Hoppe, MD, however, was just awarded a Doris Duke Charitable Foundation Award to confirm preliminary data indicating that statins – known for their cholesterol-reducing benefits – may provide new hope for finding therapeutic options for preventing or treating these debilitating pain crises in SCD.  



In the last decade or so, new research suggests that injury to the endothelial cells that line the walls of the blood vessels is a key culprit in causing the pain crises in SCD, and that such injury is actually due to a chain reaction in which nitric oxide (NO) deficiency causes increased inflammation, which in turn causes endothelial injury. Although statins are most well known for their cholesterol-reducing benefits, recent research has shown that statins may be preventing vascular dysfunction through NO-mediated anti-inflammatory effects.

"We know that SCD is characterized by chronic inflammation and sustained endothelial activation, but what is intriguing is that patients with atherosclerotic heart disease have similarly high levels of inflammation and endothelial injury," says Dr. Hoppe.

“What is intriguing is that patients with atherosclerotic heart disease have similarly high levels of inflammation and endothelial injury.”
"Recent studies have also shown that many of the clinical benefits of statins may actually be due to their ability to increase NO levels and thus stop the chain reaction that causes endothelial cell injury."

In a recent first-time pilot study, Dr. Hoppe and her colleagues tested whether or not statins could provide similar endothelial protection in patients with SCD. The study examined the effect of statin treatment on plasma nitric oxide levels and selected biomarkers of endothelial dysfunction in 26 SCD patients, with 14 of the patients on a low statin dose, and 12 of the patients the patients on a moderate statin dose.
The results were striking. Plasma nitric oxide levels increased by 23 percent in the low dose group, and by 106 percent in the moderate dose group, while biomarkers of inflammation significantly decreased in both groups in an equally dose-dependent fashion.

"Biomarkers of nitric oxide deficiency and inflammation were measured prior to treatment with statins and indicated that SCD patients in general have a steady low-grade inflammation. In addition, the four patients who experienced mild pain crises during the study showed sharp declines in nitric oxide levels and a simultaneous increase in inflammatory biomarkers," Dr. Hoppe says.

The fact that statin treatment was so effective in increasing nitric oxide levels and decreasing inflammation indicates that Dr. Hoppe and her colleagues may have just found a new approach to treating SCD pain crises. Confirmation in larger studies is needed, but the overwhelmingly positive results of the pilot study, in combination with a sound safety profile, should lead a large, randomized, placebo-controlled trials to assess whether or not statins can provide a preventative treatment for SCD pain crises.

In the mean time, however, the results netted Dr. Hoppe the Doris Duke award, which will allow Dr. Hoppe to confirm whether treatment with statins reduces the frequency and intensity of pain crises in patients with SCD.

"Our pilot study showed conclusive improvements in NO levels and downstream inflammatory markers associated with endothelial dysfunction," says Dr. Hoppe.

“The fact that the results were dose dependent suggests that increased doses may be more effective. Our hope is that these biomarker data will translate in our next study into the prevention of endothelial injury and the chain of events that causes sickle cell pain crises.”

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Thursday, May 17, 2012 12:51 PM

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