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Gene Therapy Developments for Pompe Disease

Unnisa, Zeenath; Yoon, John K; Schindler, Jeffrey W; Mason, Chris; van Til, Niek P; (2022) Gene Therapy Developments for Pompe Disease. Biomedicines , 10 (2) , Article 302. 10.3390/biomedicines10020302. Green open access

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Pompe disease is an inherited neuromuscular disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). The most severe form is infantile-onset Pompe disease, presenting shortly after birth with symptoms of cardiomyopathy, respiratory failure and skeletal muscle weakness. Late-onset Pompe disease is characterized by a slower disease progression, primarily affecting skeletal muscles. Despite recent advancements in enzyme replacement therapy management several limitations remain using this therapeutic approach, including risks of immunogenicity complications, inability to penetrate CNS tissue, and the need for life-long therapy. The next wave of promising single therapy interventions involves gene therapies, which are entering into a clinical translational stage. Both adeno-associated virus (AAV) vectors and lentiviral vector (LV)-mediated hematopoietic stem and progenitor (HSPC) gene therapy have the potential to provide effective therapy for this multisystemic disorder. Optimization of viral vector designs, providing tissue-specific expression and GAA protein modifications to enhance secretion and uptake has resulted in improved preclinical efficacy and safety data. In this review, we highlight gene therapy developments, in particular, AAV and LV HSPC-mediated gene therapy technologies, to potentially address all components of the neuromuscular associated Pompe disease pathology.

Type: Article
Title: Gene Therapy Developments for Pompe Disease
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/biomedicines10020302
Publisher version: https://doi.org/10.3390/biomedicines10020302
Language: English
Additional information: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
Keywords: Pompe disease; enzyme replacement therapy; adeno-associated viral vector; hematopoietic stem cell; lentiviral vectors
UCL classification: UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
UCL > Provost and Vice Provost Offices > UCL BEAMS
URI: https://discovery.ucl.ac.uk/id/eprint/10146077
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