- The Washington Times - Monday, November 11, 2002

Researchers have found a link between the release from malformed red blood cells of the vital protein that carries oxygen, and episodes of severe pain in people with sickle cell disease.
The discovery is leading to clinical trials to test a new treatment whether breathing nitric oxide, an important chemical that helps regulate blood pressure by relaxing blood vessels, can help sickle cell patients with their pain, said National Institutes of Health researcher Dr. Mark T. Gladwin.
The disease, in which blood cells form in an abnormal crescent shape, affects an estimated 70,000 Americans. It has no cure, though treatment can ease the periodic episodes of severe pain. The inherited condition can cause bouts of severe pain, particularly in joints and limbs, and can damage the lungs, kidneys and other vital organs.
Nitric oxide is removed from the blood plasma by hemoglobin, the compound that carries oxygen around the body, and that results in constricted blood vessels, reduced blood flow and the accompanying pain, said a team of researchers led by Dr. Gladwin.
Doctors traditionally believed the pain was caused by the deformed cells, which became sticky, clumping together and blocking blood vessels. The newly reported constricting of the blood vessels could worsen those blockages.
Hemoglobin normally is contained within blood cells it is what makes them red and that severely limits its ability to react with nitric oxide. The misshapen blood cells of sickle cell patients contain a form of hemoglobin and release a large amount of it into the blood plasma.
There, it is 1,000 times more efficient in sweeping up the nitric oxide, resulting in the constricted blood vessels, the researchers reported yesterday in the online edition of the journal Nature Medicine.
Researchers plan clinical trials involving the nitric oxide in Baltimore, Washington, Boston and possibly Oakland, Calif., in six to 12 months, said Dr. Gladwin, of NIH's National Institute of Diabetes, Digestive and Kidney Diseases.
People in an acute pain crisis will receive treatment with either nitric oxide or an inert gas as a placebo to determine if there is a difference in the response.
He said other treatments could include converting the free hemoglobin in the blood to a less-active form of the chemical that would not destroy the nitric oxide.
A remaining mystery, Dr. Gladwin said in an interview, is what causes the pain crisis to occur in sickle cell patients.
"It's like migraine," he said. "One of the mysteries is, what's the trigger?"

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