GBT440 increases hematocrit and improves biventricular function in Berkeley sickle cell disease mice

Abstract

Sickle cell disease (SCD) is a hereditary blood disorder affecting millions of people in which red blood cells become sickled and lyse easily driven by polymerization of hemoglobin. Chronically, SCD causes anemia and biventricular dysfunction. GBT440 is an experimental treatment for SCD that prevents hemoglobin polymerization. We hypothesized that 17-month-old Berkeley SCD mice treated with GBT440 would have increased hematocrit (Hct) and better biventricular function compared to untreated SCD mice. Our results demonstrate that 3 weeks of GBT440 treatment eliminated chronic anemia, increased left ventricular ejection fraction (LV EF) and stroke volume index (SVI), and improved right ventricular function. Overall, our findings support a therapeutic effect of GBT440 in vivo in a small animal model of SCD. Next steps in translating this experimental treatment to clinical trials are warranted.