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

Aims: HbE/beta-thalassemia is the most 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. In this study, we aimed to assess clinical HU response among the Bengali HbE/beta-thalassemia patients with respect to the XmnI gamma(G)globin polymorphism and elucidate the association between this polymorphism and HU response efficacy. Materials and Methods: We enrolled 49 transfusion-dependent patients with HbE/beta-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 XmnI gamma(G)globin polymorphism. Results: 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 (p < 0.001) between the XmnI polymorphism genotype and transfusion-free interval. Patients with the XmnI polymorphism were found to be good responders for HU therapy and showed increased hemoglobin levels. Conclusions: Our findings indicate that HU is a potential drug candidate for thalassemia management, particularly for HbE/beta-thalassemia. These results hold implications in repurposing HU as an effective and efficient therapy for HbE/beta-thalassemia.

Automated summary

This study found a significant correlation between the XmnI polymorphism genotype and the response to hydroxyurea (HU) therapy in patients with HbE/β-thalassemia. Patients with the XmnI polymorphism were found to be better responders to HU therapy and showed increased hemoglobin levels. These findings suggest the potential repurposing of HU as an effective therapy for HbE/β-thalassemia.