Voxelotor is an inhibitor of sickle hemoglobin polymerization that is used to treat sickle cell disease. While voxelotor has been shown to improve anemia, the clinical benefit on the brain remains to be determined. This study quantified the cerebral hemodynamic effects of voxelotor in children with sickle cell anemia (SCA) using non-invasive diffuse optical spectroscopies. Specifically, frequency-domain near-infrared spectroscopy (FDNIRS) combined with diffuse correlation spectroscopy (DCS) were used to noninvasively assess regional oxygen extraction fraction (OEF), cerebral blood volume (CBV), and an index of cerebral blood flow (CBFi). Estimates of CBFi were first validated against arterial spin-labeled magnetic resonance imaging (ASL-MRI) in 8 children with SCA ages 8-18 y. CBFi was significantly positively correlated with ASL-MRI-measured blood flow (R2 = 0.651, p = 0.015). Next, a single-center, open label pilot study was completed in 8 children with SCA ages 4-17 y on voxelotor monitored prior to treatment initiation, and at 4, 8, and 12 weeks (NCT05018728). By 4 w, both OEF and CBFi significantly decreased, and these decreases persisted to 12 w (both p < 0.05). Decreases in CBFi were significantly correlated with increases in blood hemoglobin concentration (p = 0.025), while the correlation between decreases in OEF and increases in hemoglobin trended towards significance (p = 0.12). Given that previous work has shown that oxygen extraction and blood flow are elevated in pediatric SCA compared to controls, these results suggest that voxelotor may reduce cerebral hemodynamic impairments.
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