Riociguat shows remarkable safety but underwhelming activity in patients with sickle cell disease
The exciting therapeutic potential of nitric oxide-based pharmaceuticals is the inspiration for the work of Mark Gladwin and colleagues1 in this issue of The Lancet Haematology. When sickle haemoglobin polymerises, red blood cell deformability is compromised, resulting in haemolysis and the release of free haeme. Free haemoglobin scavenges nitric oxide, an important signalling molecule, and depletes nitric oxide precursors. This nitric oxide depletion paralyses vasodilatory mechanisms and contributes to the activation of platelets, leukocytes, and endothelial cells,2 and might affect some of the devastating complications associated with sickle cell disease.