NDLI: GBT440 Inhibits Sickling of Sickle Cell Trait Blood Under In Vitro Conditions Mimicking Strenuous Exercise

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GBT440 Inhibits Sickling of Sickle Cell Trait Blood Under In Vitro Conditions Mimicking Strenuous Exercise

Content Provider	Semantic Scholar
Author	Dufu, Kobina Lehrer-Graiwer, Josh Ramos, Eleanor Oksenberg, Donna
Copyright Year	2016
Abstract	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. We report that GBT440, an agent being developed for the treatment of SCD, increases the affinity of oxygen for Hb and inhibits in vitro polymerization of a mixture of HbS and HbA that simulates SCT blood. Moreover, GBT440 prevents sickling of SCT blood under in vitro conditions mimicking strenuous exercise with hypoxia, dehydration and acidosis. Together, our results indicate that GBT440 may have the potential to protect SCT individuals from sickling-related complications during conditions that favor HbS polymerization.
File Format	PDF HTM / HTML
DOI	10.4081/hr.2016.6637
PubMed reference number	27757216
Journal	Medline
Volume Number	8
Alternate Webpage(s)	https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/30/a1/hr-2016-3-6637.PMC5062624.pdf
Alternate Webpage(s)	https://www.pagepress.org/journals/index.php/hr/article/download/6637/6475
Alternate Webpage(s)	https://doi.org/10.4081/hr.2016.6637
Journal	Hematology reports
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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