Changes in indicators of cerebral metabolic stress following treatment with voxelotor in children and adolescents with sickle cell anemia.

Voxelotor is a small molecule that reduces the polymerization of sickle hemoglobin by increasing its affinity for oxygen. In patients with sickle cell anemia, it has been postulated that increasing hemoglobin-oxygen affinity could limit oxygen offloading from hemoglobin, causing an increase in cerebral metabolic stress. To investigate this hypothetical concern, we used multimodal brain imaging to define the effects of voxelotor on cerebral blood flow and oxygen extraction. We followed four patients for 2-5 months during and/or after voxelotor therapy. This study showed no observable increase in cerebral blood flow or oxygen extraction fraction during treatment.

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© 2024 The Author(s). eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.

Déclaration de conflit d'intérêts

Andrew M. Heitzer—Consultant Fees: Global Blood Therapeutics.Clark Brown—Former employee: Legacy Global Blood Therapeutics / Pfizer; Equity ownership: Pfizer; Consultant fees: Global Blood Therapeutics; Research funding: Forma Therapeutics, Global Blood Therapeutics, Imara, Novartis, Pfizer.Mark Davis—Employee: Pfizer; Equity ownership: Pfizer; Former employee: Global Blood Therapeutics.Sandy Dixon—Employee: Pfizer; Equity ownership: Pfizer; Former employee: Global Blood Therapeutics.Jeremie Estepp—Research Funding: Global Blood Therapeutics, Forma Therapeutics, Pfizer, Eli Lilly and Co, NHLBI, ASH; Consultant Fees: Daiichi Sankyo, Esperion, and Global Blood Therapeutics. Following completion of the activities contained in this manuscript, Jeremie Estepp changed employers to Agios Pharmaceuticals, which had no role in the design of the study, analysis or interpretation of the results, or drafting of the manuscript.Cliff Takemoto—Site‐PI, Global Blood Therapeutics; Site‐PI, Forma Therapeutics; Data Safety Committee, Novartis.