GBT440 Increases Hematocrit and Improves Biventricular Function in Berkeley Sickle Cell Disease Mice-Reference-Cited by-同舟云学术

GBT440 Increases Hematocrit and Improves Biventricular Function in Berkeley Sickle Cell Disease Mice

Published:2020-12-10 Issue:3 Volume:143 Page:
ISSN:0148-0731
Container-title:Journal of Biomechanical Engineering
language:en
Short-container-title:

Author:

Gassner Ryan¹,Schreier David²,Hacker Timothy³,Tabima Diana M.²,Chesler Naomi⁴

Affiliation:

1. College of Agricultural and Life Sciences, University of Wisconsin, Madison, WI 53706

2. Department of Biomedical Engineering, University of Wisconsin, 2146 ECB, 1550 Engineering Dr., Madison, WI 53706

3. Department of Medicine, University of Wisconsin, 1685 Highland Avenue, 5158 Medical Foundation Centennial Building, Madison, WI 53705

4. Department of Biomedical Engineering, University of Wisconsin, 2146 ECB, 1550 Engineering Dr., Madison, WI 53706; Department of Medicine, University of Wisconsin, 1685 Highland Avenue, 5158 Medical Foundation Centennial Building, Madison, WI 53705

Abstract

Abstract Sickle cell disease (SCD) is a hereditary blood disorder affecting millions of people in which red blood cells (RBCs) become sickled and lyse easily driven by polymerization of hemoglobin. Chronically, SCD causes anemia and biventricular dysfunction. GBT440 is an experimental treatment for SCD that prevents hemoglobin polymerization. We hypothesized that 17-month-old Berkeley SCD mice treated with GBT440 would have increased hematocrit (Hct) and better biventricular function compared to vehicle treated SCD mice. Our results demonstrate that 3 weeks of GBT440 treatment eliminated chronic anemia, increased left ventricular ejection fraction (LVEF) and stroke volume index, and improved right ventricular function. Overall, our findings support a therapeutic effect of GBT440 in vivo in a small animal model of SCD. Next steps in investigating mechanisms of improved cardiac function are warranted.

Publisher

ASME International

Subject

Physiology (medical),Biomedical Engineering

Link

http://asmedigitalcollection.asme.org/biomechanical/article-pdf/doi/10.1115/1.4049079/6600923/bio_143_03_034501.pdf

Reference15 articles.

1. Global Burden of Sickle Cell Anaemia in Children Under Five, 2010-2050: Modeling Based on Demographics, Excess Mortality, and Interventions;PLoS Med.,2013

2. GBT440 Increases Haemoglobin Oxygen Affinity, Reduces Sickling and Prolongs RBC Half-Life in a Murine Model of Sickle Cell Disease;Br. J. Haemotol.,2016

3. Aworunse, O., 2017, “National Trends in the Use and Cost of Hospital Care in the U.S. for Sickle Cell Disease,” Doctoral dissertation, Texas Medical Center, Houston, Texas.https://digitalcommons.library.tmc.edu/dissertations/AAI10275138/

4. Prevalence of Sickle Cell Disease and Sickle Cell Trait in National Neonatal Screening Studies;Rev. Bras. Hematol. Hemoterapia,2011

5. Pathophysiology and Treatment of Pulmonary Hypertension in Sickle Cell Disease;Blood,2016