Innovative Therapies for Hemoglobin Disorders

Abstractβ-Globin gene transfer has been used as a paradigm for hematopoietic stem cell (HSC) gene therapy, but is subject to major difficulties, such as the lack of selection of genetically corrected HSCs, the need for high-level expression of the therapeutic gene, and cell-specific transgene expression. I t took more than 40 years for scientists and physicians to advance from the cloning of globin gene and discovering globin gene mutations to improving our understanding of the pathophysiological mechanisms involved, the detection of genetic modifiers, the development of animal models and gene transf er vectors, comprehensive animal testing, and demonstrations of phenotypic improvement in clinical trials, culminating in the authorization of the first gene therapy product for β-thalassemia in 2019. Research has focused mostly on the development of lentiviral gene therapy vectors expressing varia nts of the β-globin gene or, more recently, targeting a γ-globin repressor, some of which have entered clinical testing and should soon diversify the available treatments and promote price competition. These results are encouraging, but we have yet to reach the end of the story. New molecular and cellular tools, such as gene editing or the development of induced pluripotent stem cells, are being developed, heralding the emergence of alternative products, the efficacy and safety of which are being studied. Hemoglobin disorders constitute an important model for testing the pros and ...
Source: BioDrugs - Category: Drugs & Pharmacology Source Type: research