Yale-Ghana Collaboration Uncovers Natural Protective Enzyme with Therapeutic Promise for Sickle Cell Disease

A new study in HemaSphere from an international team of collaborators from Yale School of Medicine and their partner institutions in Ghana, through the SickleGenAfrica Network reports that serum heme oxygenase-1 (HO-1), an enzyme that degrades free heme and counters hemolysis-related toxicity, is markedly elevated in patients with sickle cell disease, with the strongest responses in children.

The lead author, Anna Sowa, MD, MHS, clinical associate (hematology/oncology) and PhD candidate at the Investigative Medicine Program at Yale, noted that this first large study of HO-1 in sickle cell disease, analyzing over 2,300 patients from Ghana, found that circulating HO-1 levels were about 20 times higher in patients with sickle cell disease compared to levels reported in healthy populations. Notably, this protective enzyme was also nearly threefold higher in children than in adults with sickle cell disease, a pattern consistent across sickle cell subtypes.

With these findings, Sowa says the next steps for the SickleGenAfrica Network are to better define the role and mechanisms of HO-1 in people with sickle cell disease, including its genetic regulation. These insights would open the door to therapeutic strategies that boost HO-1 expression or activity, or deliver synthetic HO, in hopes to reduce complications in sickle cell disease.

This work highlights the importance of sustained international partnership in addressing a condition that affects about 7.7 million people globally, with Sub-Saharan Africa bearing the greatest burden, where up to about 2% of births are affected, and about 100,000 affected individuals in the United States.

Other co-authors include Jeffrey R. Gruen, MD, professor of pediatrics (neonatology) and of genetics at Yale School of Medicine, Solomon Ofori-Acquah, PhD from Emory University and the founding director of the West African Genetic Medicine Centre, and other collaborators of the SickleGenAfrica Network.

You can read the full paper online from HemaSphere.