Preclinical therapeutics for sickle cell disease: modern developments and future considerations

Most of the current treatment modalities for sickle hemoglobinopathy are disease-modifying rather than curative. Therefore, there is a need for effective treatment of complications of sickle cell disease (SCD) that impair quality of life. This need drives the evaluation of preclinical therapeutics in search of new treatment modalities.

Interventions are likely to progress from research to clinical practice, their potential impact, and future directions in SCD care: HbF inducers, pyruvate kinase activators, anti-selectin P monoclonal antibodies, allosteric Hb modifiers, proactive treatment of cerebral artery conditional blood velocity, multimodal, and gene therapy. Established treatment modalities (e.g with hydroxyurea) are not included because these have advanced well beyond the preclinical stage of therapeutics. Information dated 2025 backward was obtained from Medline, PubMed, and other public sources.

Places for the conduct of preclinical studies ought to include areas of high SCD prevalence. Limited resources currently hinder universal accessibility of curative SCD therapies in these places. The recent approval of non-viral gene therapy for SCD and the number of preclinical therapeutics in development bring realistic expectation that curative and disease-modifying interventions, such as multimodal therapy and proactive treatment of cerebral artery conditional blood velocity to prevent stroke, will become standard care.