Drug repurposing: Hydroxyurea therapy improves the transfusion-free interval in HbE/beta thalassemia major patients with Xmn1 polymorphism

Abstract

AimsHbE/{beta}-thalassemia is the prevalent form of severe {beta}-thalassemia in Asian countries. Hydroxyurea (HU) is the most common drug used for the management of sickle-cell anemia but not thalassemia. Here, we aimed to assess clinical HU response among patients with HbE/{beta}-thalassemia with respect to Xmn1 {gamma}Gglobin polymorphism and elucidate the association between this polymorphism and HU response efficacy. MethodsWe enrolled 49 transfusion-dependent patients with HbE/{beta}-thalassemia. Fetal hemoglobin level was measured using High-performance liquid chromatography (HPLC) and complete blood count was determined pre- and post-HU therapy. Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP) was performed for genotyping Xmn1 {gamma}Gglobin polymorphism. ResultsA total of 30 (61.22%) patients were found to be responders, whereas the remaining 19 (38.78%) were non-responders. We found 33 patients with heterozygous (C/T) and three with homozygous mutant (T/T) genotype status. We obtained a statistically significant correlation (p < 0.001) between Xmn1 polymorphism and transfusion-free interval. Patients with Xmn1 polymorphism were found to be good responders for HU therapy and showed increased hemoglobin levels. ConclusionsOur findings indicate that HU is a potential drug candidate for thalassemia management, particularly HbE/{beta}-thalassemia. The results hold implications in repurposing HU as an effective and efficient therapy for HbE/{beta}-thalassemia.