A Potential New Therapeutic Option for Sickle Cell Disease and β-Thalassemia
Oct 22, 2019, 08:00 ET
WASHINGTON, Oct. 22, 2019 /PRNewswire/ -- An article published in Experimental Biology and Medicine (Volume 244, Issue 14, October 2019) (https://journals.sagepub.com/doi/pdf/10.1177/1535370219872995) reports a possible future treatment option for patients with sickle cell disease and β-thalassemia. The study led by Dr. Li Liu in the Department of Biological Sciences at the University of Texas at Dallas in Richardson, Texas (USA), reports that δ-aminolevulinate (ALA), a heme precursor, can activate fetal γ-globin expression in erythroid cell systems.
Sickle cell disease (SCD) and β-thalassemia are common forms of inherited blood diseases, termed hemoglobinopathies. These disorders negatively impact the quality of life and survival for millions of individuals throughout the world. These diseases are caused by mutations in the adult β-globin gene that ultimately result in the production of abnormal hemoglobins. Hemoglobin is the major protein inside red blood cells and delivers oxygen to cells throughout the body.
Prior studies have demonstrated that increased levels of the fetal γ-globin gene product can lessen the severity in SCD and β-thalassemia patients. Hydroxyurea, the first FDA approved therapeutic for SCD, works in part by increasing fetal γ-globin. Nonetheless, some patients do not respond to treatment with Hydroxyurea. Thus, there is an urgent need to identify new strategies that will increase γ-globin levels in patients suffering from SCD and β-thalassemia.
In the current study, Dr. Liu and colleagues investigated the effects of ALA on γ-globin expression. Previous studies have shown that exogenous ALA enhances heme synthesis, globin gene expression and hemoglobin production. However, the mechanisms leading to the effects of ALA on γ-globin expression have not been investigated. This study reports that ALA preferentially activates γ-globin transcription and translation, thereby inducing fetal hemoglobin synthesis. Mechanistic studies reveal that heme biosynthesis and reactive oxygen species mediate the ability of ALA to induce γ-globin expression. Dr. Liu said, "These results support future studies to explore the potential of stimulating intracellular heme biosynthesis by ALA or similar compounds as a novel therapeutic strategy for treating SCD and beta-thalassemia."
Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology & Medicine, said, "Researchers in the sickle cell field are currently pursuing many clinical trials that would expand the FDA approved SCD therapeutic choices beyond Hydroxyurea, and the more recently approved Endari. Liu et al have provided in vitro evidence that ALA, through induction of heme biosynthesis, should be considered as a possible future therapeutic option."
Experimental Biology and Medicine is a global journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. The journal was first established in 1903. Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership, visit www.sebm.org. If interested in publishing in the journal, please visit http://ebm.sagepub.com.
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