Drug Repurposing: Hydroxyurea Therapy Improves the Transfusion-Free Interval in HbE/Beta-Thalassemia-Major Patients with the I Polymorphism.

HbE/β-thalassemia is the most prevalent form of severe β-thalassemia in Asian countries. Hydroxyurea (HU) is the most common drug used for the management of sickle-cell anemia but not thalassemia. In this study, we aimed to assess clinical HU response among the Bengali HbE/β-thalassemia patients with respect to the I γglobin polymorphism and elucidate the association between this polymorphism and HU response efficacy. We enrolled 49 transfusion-dependent patients with HbE/β-thalassemia. Fetal hemoglobin levels were measured using high-performance liquid chromatography and complete blood counts were determined pre- and post-HU therapy. Polymerase chain reaction-restriction fragment length polymorphism analyses were performed for genotyping the I γglobin polymorphism. A total of 30 (61.22%) patients were found to be responders, whereas the remaining 19 (38.78%) were nonresponders. We found 33 patients with the heterozygous (C/T) and three with the homozygous mutant (T/T) genotype status. We obtained a statistically significant correlation ( < 0.001) between the I polymorphism genotype and transfusion-free interval. Patients with the I polymorphism were found to be good responders for HU therapy and showed increased hemoglobin levels. Our findings indicate that HU is a potential drug candidate for thalassemia management, particularly for HbE/β-thalassemia. These results hold implications in repurposing HU as an effective and efficient therapy for HbE/β-thalassemia.