Study Points to Role of Nitric Oxide in New Treatments for Sickle Cell Anemia

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Increasing levels of nitric oxide in the blood may offer new options for treating sickle cell anemia, the most common inherited blood disorder in the country.

In a study described in this month’s Journal of Clinical Investigation, researchers at the Warren Grant Magnuson Clinical Center at the National Institutes of Health are examining how nitric oxide acts on hemoglobin, the oxygen-carrying molecule in red blood cells. Nitric oxide, a gas produced in many parts of the body, relaxes the smooth muscle cells in blood vessels. 

As the muscles relax, the vessels expand and allow more blood to pass through. Improving blood flow is a critical aspect in treating the painful and potentially deadly complications associated with sickle cell anemia.

The Clinical Center (CC) study demonstrates that when nitric oxide is inhaled, it binds to hemoglobin. Once attached, the gas hitches a ride through the blood stream, and may dilate vessels as it passes through.

“This study is the first clinical demonstration of how nitric oxide binds to hemoglobin and that hemoglobin carries the gas as blood moves through the body,” noted Dr. Frederick Ognibene of the CC’s Critical Care Medicine Department.

In sickle cell anemia, hemoglobin molecules cluster into rigid spikes as oxygen is lost. The result is misshapen blood cells that slow blood flow and can block vessels entirely. When blood flow is disrupted, oxygen can’t be delivered to the body. That causes painful and potentially deadly damage to organs and tissues.

“Without oxygen, tissues die, and dying tissue hurts,” Dr. Mark T. Gladwin, Critical Care Medicine Department, NIH CC, the study’s principal investigator. “Some patients describe the pain as like a sledgehammer slamming bone.”

Collaborating on the continuing investigations are the National Institute of Diabetes, Digestive, and Kidney Diseases and the National Heart, Lung, and Blood Institute. The NIH researchers hope that these early studies will lead to new treatments for the life-threatening complications of this yet-incurable disease.

Next step is to use magnetic resonance imaging to map changes in blood flow to certain muscle groups following nitric oxide inhalation therapy, researchers say.

“Sickle cell anemia is a painful and debilitating disease that affects thousands of Americans,” said Dr. John I. Gallin, CC director. “The Clinical Center’s investigations in this area reflect our commitment to developing new and better therapies through innovative clinical research.”

Sickle cell anemia is most prevalent in African-Americans. About 1 in every 500 African-Americans have the disease; 1 in 12 carry the sickle cell trait. 

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