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Augmentation of fetal hemoglobin (HbF) production has been an enduring therapeutic objective in β-thalassemia patients for which hydroxyurea (HU) has largely been the drug of choice and the most cost-effective approach. A serum metabolomics study on 40 patients with β-thalassemia prior to and after administration of HU was done along with healthy controls. Treated patients were divided further into non-responders (NR), partial (PR) and good (GR) per their response. 25 metabolites that were altered before HU therapy at p ≤ 0.05 and fold change >2.0 in β-thalassemia patients; started reverting towards healthy group after HU treatment. A prediction model based on another set of 70 HU treated patients showed a good separation of GR from untreated β-thalassemia patients with an overall accuracy of 76.37%. Metabolic pathway analysis revealed that various important pathways that were disturbed in β-thalassemia were reverted after treatment with HU and among them linoleic acid pathway was most impactfully improved in HU treated patients which is a precursor of important signaling molecules. In conclusion, this study indicates that HU is a good treatment option for β-thalassemia patients because in addition to reducing blood transfusion burden it also ameliorates disease complications by shifting body metabolism towards normal.

Hydroxyurea Treated β-Thalassemia Children Demonstrate a Shift in Metabolism Towards Healthy Pattern