Investigates CYB5R3 variant's effect on riociguat efficacy in sickle cell disease, suggesting genetic influence on treatment outcomes.
Sickle cell disease attenuates nitric oxide signaling, limiting soluble guanylyl cyclase (sGC) stimulation needed for hemo-vascular function. Cytochrome b5 reductase 3 (CYB5R3) regulates sGC activity and expression. We show CYB5R3 T117S associates with reduced efficacy of the sGC stimulator riociguat. (NCT02633397)
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Wood et al. (2026) studied this question.
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