Drug Repurposing in Sickle Cell Disease: Evaluating Imatinib as a Therapeutic Candidate

Sickle cell disease (SCD) is an inherited hemolytic hemoglobinopathy characterized by chronic hemolysis, vaso-occlusive pain crises, and progressive organ damage. Hydroxyurea, often combined with analgesics, remains a mainstay therapy, but may provide insufficient relief during active disease episodes. Drug repurposing offers a practical alternative where de novo drug development is limited, providing faster and more cost-effective therapeutic options. Imatinib (Gleevec), a tyrosine kinase inhibitor primarily used for chronic myeloid leukemia, has gained attention as a potential repurposed therapy for SCD. This narrative review provides a theoretical framework for evaluating imatinib's potential applications in mitigating key pathophysiological processes in SCD. Examination of the molecular pathways shared between imatinib's targets and the pathogenesis of SCD has yielded mixed findings: some studies suggest imatinib may reduce hemolysis and alleviate pain crises, while others have not supported such benefits. Direct investigations of imatinib in the context of SCD are limited, yet available evidence has reported potentially valuable outcomes, including decreased hospitalization rates, shorter hospital durations, and reduced organ damage. Current evidence remains insufficient for definitive conclusions, underscoring the need for well-designed clinical and translational studies to clarify the feasibility of incorporating imatinib into SCD management. SUMMARY: Imatinib has actions on signaling pathways with potential clinical relevance to sickle cell disease, such as reduction of inflammation, vaso-occlusive crises, and opioid tolerance. Reports of use in patients with sickle cell disease suggest potential for reducing the frequency of vaso-occlusive crises.