Enzyme mutations could be key to developing new drugs that will protect children with sickle cell anemia from vascular clots and strokes.
An enzyme known as NPP1, encoded by the gene associated with stroke protection, is part of a family of enzymes that encourages the coagulation of blood on vascular surfaces.
Too much clotting on the vascular lining can lead to thrombosis and stroke. By demonstrating that NPP1 can induce platelet aggregation at low concentrations (on the vascular lining, for example), the team established a direct role for the enzyme in thrombotic stroke.
“Our findings strongly suggest that NPP1 inhibitors would confer some level of stroke protection to patients at risk for thrombotic stroke, especially to children with sickle cell anemia in whom the NPP1 variation was identified,” says Demetrios Braddock, associate professor of pathology at Yale School of Medicine and senior author of the study in the Journal of Biological Chemistry.
The team also determined the molecular structure of a close relative of NPP1 called NPP4, which revealed the molecular details of the target site for new inhibitors directed against the gene—further enabling the possible design of novel anti-stroke drugs.
Researchers at Yale and the Geisel School of Medicine at Dartmouth contributed to the study, which was supported by the Connecticut Department of Public Health.
Source: Yale University