Full Description
Hemoglobin defects, specifically sickle cell disease & thalassemia, combined, constitute the most common monogenic disorders in the world. In fact, nearly 2% of the world's population carries a globin gene mutation. The transfer of the corrective globin gene through the HSC compartment by allogeneic HSC transplantation (HSCT) has already proven curative in both SCD and thalassemia patients, and provides the proof of concept that genetic manipulation of the defective organ might be equally therapeutic. However, procedural toxicities and the requirement of an HLA-matched sibling donor limit this approach to a fraction of affected individuals. The editors review the progress & the state of the field in HSCT for hemoglobinopathies & shed light on the major changes expected in the next decade. Although allogeneic HSCT is a curative option, it is limited by the availability of matched donors, which are often available only to 15-20% of patients. An alternative to allogeneic HS
CT is genetic correction of autologous HSCs, to overcome donor availability & immune side effects. This Book reviews the progress made on additive gene therapy approaches & the current state of the field. Finally, targeted genetic correction is emerging as a novel therapeutic strategy in the hemoglobinopathies. Although ideal, the inefficiency of targeted correction was rate limiting for translation of this technology to the clinic. With advancements in zinc finger nucleases and TALE endonuclease mediated targeted correction, correction frequencies in hematopoietic stem cells is now reaching levels that may become clinically relevant. Furthermore, the ability to generate autologous embryonic stem cell like cells from primary somatic cells (skin fibroblasts or hematopoietic cells) of the affected individual has allowed for the potential application of genetic correction strategies.This Book reviews upcoming genetic strategies to reactivate fetal hemoglobin production and research advances.
Contents
Introduction and clinical features of b -thalassemias and sickle cell disease (SCD).- Genetic basis and genetic modifiers of the b -thalassemias and SCD.- Current Standards of care and long term outcomes of Thalassemia and SCD.- Allogeneic/ matched related transplantation for the b -thalassemias and SCD.- Alternative donor /unrelated donor transplants for the b -thalassemias and SCD.- Gene addition strategies for the b -thalassemias and SCD.- Genetic reactivation of fetal hemoglobin for b -thalassemia and SCD.- Gene correction strategies for the b -thalassemias and SCD.- iPSC gene and cell therapy for the b -thalassemias and SCD.- Future Prospects for Gene and Cell Therapies for Hemoglobinopathies.
