John K Yoon, Jeffrey W Schindler, Mariana Loperfido, Cristina Baricordi, Mark P DeAndrade, Mary E Jacobs, Christopher Treleaven, Robert N Plasschaert, Aimin Yan, Cecilia N Barese, Yildirim Dogan, Vicky Ping Chen, Claudia Fiorini, Fritz Hull, Luigi Barbarossa, Zeenath Unnisa, Daniel Ivanov, Robert H Kutner, Swaroopa Guda, Christine Oborski, Tim Maiwald, Véronique Michaud, Michael Rothe, Axel Schambach, Richard Pfeifer, Chris Mason, Luca Biasco, Niek P van Til
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引用次数: 0
Abstract
Pompe disease, a rare genetic neuromuscular disorder, is caused by a deficiency of acid alpha-glucosidase (GAA), leading to an accumulation of glycogen in lysosomes, and resulting in the progressive development of muscle weakness. The current standard treatment, enzyme replacement therapy (ERT), is not curative and has limitations such as poor penetration into skeletal muscle and both the central and peripheral nervous systems, a risk of immune responses against the recombinant enzyme, and the requirement for high doses and frequent infusions. To overcome these limitations, lentiviral vector-mediated hematopoietic stem and progenitor cell (HSPC) gene therapy has been proposed as a next-generation approach for treating Pompe disease. This study demonstrates the potential of lentiviral HSPC gene therapy to reverse the pathological effects of Pompe disease in a preclinical mouse model. It includes a comprehensive safety assessment via integration site analysis, along with single-cell RNA sequencing analysis of central nervous tissue samples to gain insights into the underlying mechanisms of phenotype correction.
期刊介绍:
Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.