Sickle Cell Disease (SCD) is the most common inherited hematologic disorder, affecting over 100,000 people in the US, and millions worldwide. The disease occurs as a result of a single point mutation affecting hemoglobin (Hb) in red blood cells (RBCs). Under hypoxia, low oxygen conditions, or when HbS becomes deoxygenated (deoxy-HbS), it polymerizes causing sickling of RBCs, leading to several debilitating symptoms such as vaso-occlusion, oxidative stress, inflammation, hemolysis, painful crises

The technology

Pyruvate kinase plays a key role in glycolysis; involved in 50% ATP production that drives many cellular functions, as well as 2,3-bisphosphoglycertae (2,3-BPG) production that serves a critical function in hemoglobin (Hb) tissue oxygenation. Reduced ATP level as a result of dysfunctional production of pyruvate kinase leads to hemolysis and chronic anemia responsible in part for SCD pathogenesis. Elevated 2,3-BPG in RBCs as a resulted of a compensatory mechanism to increase tissue oxygenation exacerbates sickling of RBCs. The novel drug targets pyruvate kinase to increase ATP production with concomitant decrease of 2,3-BPG that is expected to lead to a novel treatment for sickle cell disease.