@article{discovery10107977, note = {@ 2020 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).}, title = {Lentiviral Hematopoietic Stem Cell Gene Therapy Rescues Clinical Phenotypes in a Murine Model of Pompe Disease}, journal = {Molecular Therapy - Methods and Clinical Development}, pages = {558--570}, month = {September}, volume = {18}, year = {2020}, keywords = {GAA, Pompe disease, acid alpha-glucosidase, erythroid-specific enhancer, hematopoietic stem cell gene therapy, lentiviral vector, lysosomal storage disorders, personalized medicine}, issn = {2329-0501}, abstract = {Pompe disease is a lysosomal storage disorder caused by malfunctions of the acid alpha-glucosidase (GAA) enzyme with a consequent toxic accumulation of glycogen in cells. Muscle wasting and hypertrophic cardiomyopathy are the most common clinical signs that can lead to cardiac and respiratory failure within the first year of age in the more severe infantile forms. Currently available treatments have significant limitations and are not curative, highlighting a need for the development of alternative therapies. In this study, we investigated the use of a clinically relevant lentiviral vector to deliver systemically GAA through genetic modification of hematopoietic stem and progenitor cells (HSPCs). The overexpression of GAA in human HSPCs did not exert any toxic effect on this cell population, which conserved its stem cell capacity in xenograft experiments. In a murine model of Pompe disease treated at young age, we observed phenotypic correction of heart and muscle function with a significant reduction of glycogen accumulation in tissues after 6�months of treatment. These findings suggest that lentiviral-mediated HSPC gene therapy can be a safe alternative therapy for Pompe disease.}, url = {http://dx.doi.org/10.1016/j.omtm.2020.07.001}, author = {Piras, G and Montiel-Equihua, C and Chan, Y-KA and Wantuch, S and Stuckey, D and Burke, D and Prunty, H and Phadke, R and Chambers, D and Partida-Gaytan, A and Leon-Rico, D and Panchal, N and Whitmore, K and Calero, M and Benedetti, S and Santilli, G and Thrasher, AJ and Gaspar, HB} }