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

Abstract

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 alters hematological, biochemical and inflammatory biomarkers in Brazilian children with SCA: Investigating associations with βS haplotype and α-thalassemia

“…Furthermore, these findings suggest that, in addition to inducing HbF synthesis, HU can also alter metabolic and hepatic biomarkers by way of yet unknown direct or indirect mechanisms. A recent study performed in individuals with β-thalassemia demonstrated the effects of HU on the metabolic profile [35]. Previous studies also reported the effectiveness of HU for the treatment and prevention of proteinuria in individuals with SCD [36–38].…”

Identification of Circulating Endocan-1 and Ether Phospholipids as Biomarkers for Complications in Thalassemia Patients

“…Untargeted lipidomics approaches have emerged as a useful tool for the discovery of underlying disease mechanisms and novel biomarkers [32,33]. Only a few metabolomics studies have been conducted in thalassemia patients, yet none used a comprehensive untargeted lipidomic approach, and only one study was conducted using adult thalassemia patients [17,[34][35][36].…”

“…Before the onset of clinically detectable symptoms, alterations in serum metabolites offers a potential diagnostic biomarker for disease status and predicting response to treatment [15][16][17]. While previous studies identified lipid metabolism as being impacted by the disease and its treatment, the coverage of lipids was limited, mostly to fatty acids.…”

Novel genetic therapeutic approaches for modulating the severity of β‑thalassemia (Review)

“…Augmentation of HbF through the use of different pharmaceutical drugs is used to modulate the severity of thalassemia. Among these drugs, hydroxyurea is a good and cost-effective drug that normalizes the activity of several signalling pathways resulting in augmented HbF production, which ultimately results in reduction in the frequency of blood transfusions required (24). Allogenic (hemopoietic cell) transplantation is a promising cure for thalassemia; however, there are several hurdles preventing its use: Limited availability of Human Leukocyte Antigen (HLA)-identical donors, graft rejection in certain cases and the role of iron toxicity in haematopoietic stem cell transplantation (HSCT) rejection or failure (25).…”

“…Hydroxyurea not only augments the HbF levels, but also increases the levels of total haemoglobin in the body. Its effectiveness is dependent on the genetic makeup of the patient, and it has proven to be a suitable treatment option for several thalassemia major patients (24).…”