dipyridamole + magnesium

A combination therapy consisting of the small molecules dipyridamole and magnesium, investigated by the Children's Hospital Medical Center, Cincinnati, for the treatment of sickle cell anemia. The therapeutic rationale focuses on preventing red blood cell dehydration, a key driver of sickle cell pathology. Dipyridamole acts by inhibiting the sickle-induced (SI) passive cation leak pathway, while magnesium targets the abnormal potassium-chloride cotransport (KCC) mechanism. By inhibiting these transport pathways, the combination aims to maintain cellular hydration and reduce the concentration of sickle hemoglobin, thereby slowing the rate of polymerization and improving outcomes in patients with homozygous sickle cell disease (Hb SS).