One of the world’s most prominent physicians in sickle cell disease, or SCD, research and treatment talked about promising therapies in the pipeline during a visit to St. Louis on October 29.
Dr. David G. Nathan is president emeritus of the Dana-Farber Cancer Institute and the Robert A. Stranahan distinguished professor of Pediatrics and professor of Medicine at Harvard Medical School.
Nathan’s visit to Washington University and St. Louis Children’s Hospital was the first Aaron Ardoin State of Sickle Cell Disease Visiting Professorship, which will be an annual lecture to increase awareness and support research to find a cure for SCD.
Aaron Ardoin lived in Chesterfield and graduated from Parkway Central and Florida A&M. He also completed an internship at World Wide Technology. Just weeks after earning an MBA, Ardoin died in 2004 of sickle beta-thalassemia plus, a rare form of sickle cell disease.
The Visiting Professorship is presented by David and Thelma Steward and the World Wide Technology team, through their support of the Aaron Ardoin Foundation for Sickle Cell Research and Education.
“A visiting professorship on sickle cell disease helps to open the lines of communication within the medical community,” said renowned sickle cell physician, Dr. Michael DeBaun at St. Louis Children’s Hospital. “It also helps to keep sickle cell visible among researcher. We are fortunate to have a physician of Dr. Nathan’s stature to launch this much-needed initiative.”
During the lecture, Nathan gave an historical perspective to sickle cell disease treatment and its manifestations in other parts of the world, like Saudi Arabia, discussed work in animal studies that have had favorable results by blocking inflammation receptors and cell responses found in the most common complication of SCD, acute chest syndrome.
“We are going after chest syndrome because this is the most lethal, after sudden death in infancy – this is by far the most serious problem in sickle cell disease,” Nathan said.
Nathan said the current FDA-approved treatment of hydroxyurea should be standard protocol for all sickle cell patients, barring some other medical reason.
Hydroxyurea is a synthetic medication used to treat the severe pain associated with SCD. It works by increasing the amount of fetal hemoglobin (hemoglobin F) in the blood (this form of hemoglobin is resistant to sickling of the red blood cells). There are drawbacks to the compound. Its success varies, and hydroxyurea can have toxic, even fatal side effects.
Nathan said the real actor in this equation is fetal hemoglobin, and research in several cities is looking at it. Fetal hemoglobin is produced by all humans, but fades off following birth. Hemoglobin is the pigment-carrying protein in blood that gives it a red color.
“The ultimate answer to thalassemia and sickle cell disease is fetal hemoglobin. If we can get that up, there will be no disease in the patient – or very little disease in the patient if we can get it up and broad enough in all the cells,” Nathan said.
He explained the process in detail.
“If you look at the developing fetus…after the yolk sac, after all of the embryonic genes disappear, gamma genes turn on with alpha genes, then the fetus makes nothing but fetal hemoglobin. And just before birth, gamma switches off and beta turns on, “ he said.
“This is why on the first day of life or the first few days of life, first months of life, patients with sickle cell anemia or thalassemia don’t have any illness. Why don’t they have any illness? Because they had such high fetal hemoglobin.”
Research now in progress in the U.S. is poised to bring relief to thousands of patients worldwide if sufficiently affordable drugs that regulate fetal hemoglobin can be identified, according to Nathan.
There are several types of sickle cell disease, which is a genetic blood disorder. The type of sickle cell disease is determined by the genes a person has for hemoglobin. Each person has two genes for hemoglobin (one each from mother and father). The gene for normal hemoglobin is A; the sickle gene is S; and other genes include ß for beta thalassemia and hemoglobin C which is mildly abnormal. The three most common types of sickle cell disease are sickle cell anemia (SS genes), sickle-hemoglobin C disease (SC genes) and sickle beta-thalassemia (Sß genes). With sickle cell disease, red blood cells become rigid, sickle shaped and don’t carry enough oxygen to the cells. SCD is a life-threatening disease can cause a variety of complications, including excruciating pain, fatigue, anemia; swelling of the hands and feet; death of portions of the bone, leg ulcers and damage to the eyes and vital organs.
