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Gbt440 and SCD

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https://www.readbyqxmd.com/read/30046415/impact-of-voxelotor-gbt440-on-unconjugated-bilirubin-and-jaundice-in-sickle-cell-disease
#1
Paul Telfer, Irene Agodoa, Kathleen M Fox, Laurie Burke, Timothy Mant, Marzena Jurek, Margaret Tonda, Josh Lehrer-Graiwer
For many patients with sickle cell disease (SCD), jaundice is a significant clinical disease manifestation that impacts on patient well-being. We report a case of a patient with SCD and chronic jaundice treated with voxelotor (GBT440), a novel small molecule hemoglobin oxygen affinity modulator and potential disease-modifying therapy for SCD. The case patient is a 27-year-old Black male with a long history of SCD with clinical jaundice and scleral icterus. After starting voxelotor, the patient reported that his jaundice cleared within one week, and that he felt much better with more energy, and was relieved after his eyes cleared...
May 14, 2018: Hematology Reports
https://www.readbyqxmd.com/read/29660913/gbt440-improves-red-blood-cell-deformability-and-reduces-viscosity-of-sickle-cell-blood-under-deoxygenated-conditions
#2
Kobina Dufu, Mira Patel, Donna Oksenberg, Pedro Cabrales
BACKGROUND: In sickle cell disease (SCD), polymerization of hemoglobin S (HbS) leads to the formation of rigid, non-deformable sickled RBCs. Loss of RBC deformability, sickling and irreversible membrane damage causes abnormal blood rheology, and increases viscosity which contributes to vasoocclusion and other SCD pathophysiology. GBT440 (generic name voxelotor) is a novel anti-polymerization and anti-sickling agent currently undergoing clinical evaluation for the treatment of SCD. OBJECTIVE: The purpose of this study was to determine the effects of GBT440 on deformability of sickle RBCs (SS RBCs) and the hyperviscosity of sickle cell blood (SS blood)...
April 13, 2018: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/27757216/gbt440-inhibits-sickling-of-sickle-cell-trait-blood-under-in-vitro-conditions-mimicking-strenuous-exercise
#3
Kobina Dufu, Josh Lehrer-Graiwer, Eleanor Ramos, Donna Oksenberg
In sickle cell trait (SCT), hemoglobin A (HbA) and S (HbS) are co-expressed in each red blood cell (RBC). While homozygous expression of HbS (HbSS) leads to polymerization and sickling of RBCs resulting in sickle cell disease (SCD) characterized by hemolytic anemia, painful vaso-occlusive episodes and shortened life-span, SCT is considered a benign condition usually with minor or no complications related to sickling. However, physical activities that cause increased tissue oxygen demand, dehydration and/or metabolic acidosis leads to increased HbS polymerization and life-threatening complications including death...
September 28, 2016: Hematology Reports
https://www.readbyqxmd.com/read/27378309/gbt440-increases-haemoglobin-oxygen-affinity-reduces-sickling-and-prolongs-rbc-half-life-in-a-murine-model-of-sickle-cell-disease
#4
Donna Oksenberg, Kobina Dufu, Mira P Patel, Chihyuan Chuang, Zhe Li, Qing Xu, Abel Silva-Garcia, Chengjing Zhou, Athiwat Hutchaleelaha, Larysa Patskovska, Yury Patskovsky, Steven C Almo, Uma Sinha, Brian W Metcalf, David R Archer
A major driver of the pathophysiology of sickle cell disease (SCD) is polymerization of deoxygenated haemoglobin S (HbS), which leads to sickling and destruction of red blood cells (RBCs) and end-organ damage. Pharmacologically increasing the proportion of oxygenated HbS in RBCs may inhibit polymerization, prevent sickling and provide long term disease modification. We report that GBT440, a small molecule which binds to the N-terminal α chain of Hb, increases HbS affinity for oxygen, delays in vitro HbS polymerization and prevents sickling of RBCs...
October 2016: British Journal of Haematology
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