Dr. Mark T. Gladwin Leads Global Charge Against Sickle Cell Disease

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In a groundbreaking move that could revolutionize the treatment of Sickle Cell Disease (SCD), the University of Maryland School of Medicine has taken a significant step forward. Under the guidance of Dr. Mark T. Gladwin, a renowned figure in medical research, an international initiative is underway to transform the care and outcomes for millions suffering from this debilitating genetic disorder. SCD, which causes red blood cells to deform into a sickle shape, inflicts severe pain, organ damage, and profound impacts on the lives of patients and their families, with a disproportionate effect on the Black community worldwide.

Dr. Gladwin’s initiative is centered around a pioneering multicenter clinical trial, sponsored by the National Institutes of Health. This trial, spanning 22 sites in Brazil, France, and the United States, aims to evaluate the efficacy of red cell exchange transfusion. This method involves replacing the abnormal, sickle-shaped cells with healthy ones, potentially offering a new lease on life for those with SCD by preventing organ damage and extending lifespans.

The SCD-CARRE trial, as it is known, specifically targets patients at high risk of severe complications from SCD. It compares the outcomes of 150 patients receiving standard care against those undergoing monthly red blood cell exchanges for a year. While traditional blood transfusions are common in managing SCD, they carry risks such as iron toxicity. Red cell exchange transfusion presents a potentially superior alternative, despite its complexity and resource demands.

“Approximately 30 percent of patients with sickle cell disease develop serious organ damage, such as cardiopulmonary complications, and kidney or liver failure, with the risks steadily increasing with age,” said Dr. Gladwin, who is the John Z. and Akiko K. Bowers Distinguished Professor and Dean of UMSOM, and Vice President for Medical Affairs at University of Maryland, Baltimore. “The goal of the study is to determine whether red cell exchange can lower deaths, reduce hospitalizations, and slow down or reverse the development of major end-stage organ damage.”

Dr. Gladwin has not only been instrumental in launching this trial but has also contributed significantly to the understanding of SCD’s impact on the body. His research has highlighted the critical role of nitric oxide in vascular health and how its rapid consumption in SCD patients leads to complications. 

One of his key discoveries is nitric oxide resistance, caused by the scavenging of nitric oxide by free hemoglobin released during hemolysis, which is linked to pulmonary hypertension—a dangerous increase in blood pressure in the lung arteries.

Pulmonary hypertension manifests as shortness of breath, fainting, fatigue, and chest pain, severely affecting cardiovascular health in SCD patients. Dr. Gladwin’s work aims to alleviate these symptoms by pioneering treatments that replenish nitric oxide levels, including therapies that can be administered intravenously, orally, or inhaled.

The significance of Dr. Gladwin’s contributions cannot be overstated. Through his leadership in the SCD-CARRE trial and his innovative research into the biochemistry and vascular biology of SCD, he is not only advancing scientific understanding but also paving the way for new treatments that promise to improve the lives of those affected by SCD. His efforts exemplify the University of Maryland School of Medicine’s commitment to addressing some of the most pressing health challenges facing the world today.

Thanks to Dr. Gladwin and his team’s pioneering work, there is newfound hope for people living with Sickle Cell Disease. The promise of extended lives, reduced hospital stays, and halted or reversed organ damage stands as a beacon of hope, heralding a brighter, healthier future for millions worldwide affected by this genetic disorder.