ABSTRACT
To date, the main modalities that have improved survival and quality of life in sickle cell disease (SCD) have been newborn screening, penicillin prophylaxis, prompt attention to fever, transcranial doppler screening for stroke prevention, use of hydroxyurea, and access to safe transfusions. SCD is caused by a genetic mutation in the beta-globin chain of hemoglobin. This leads to the formation of a sickle hemoglobin (HbS) that undergoes conformational changes (sickling) under deoxygenated conditions. Understanding the mechanisms underlying this disease will lead to the development of targeted approaches to treatment, as opposed to the current emphasis on nonspecific supportive and preventive therapies. Targeted SCD therapies can be categorized into four groups based on pathophysiology: HbF induction and anti-sickling, inhibition of vaso-occlusion, targeting inflammation, and gene therapy. With novel targeted therapies being developed daily, the future of SCD treatments is bright. These drugs may influence pain and end-organ failure by disease-modifying mechanisms. The disparity in SCD treatment between high- and low-resource nations is an issue despite this promising medical aspect. Strategic campaigns are desperately needed to ensure that all children with SCD have access to care, beginning with successful newborn screening and follow-up programs. Only then will most patients see a substantial and additive effect from the new therapies.
