Mullagulova, A.; Shaimardanova, A.; Solovyeva, V.; Mukhamedshina, Y.; Chulpanova, D.; Kostennikov, A.; Issa, S.; Rizvanov, A. Safety and Efficacy of Intravenous and Intrathecal Delivery of AAV9-Mediated ARSA in Minipigs. Int. J. Mol. Sci.2023, 24, 9204.
Mullagulova, A.; Shaimardanova, A.; Solovyeva, V.; Mukhamedshina, Y.; Chulpanova, D.; Kostennikov, A.; Issa, S.; Rizvanov, A. Safety and Efficacy of Intravenous and Intrathecal Delivery of AAV9-Mediated ARSA in Minipigs. Int. J. Mol. Sci. 2023, 24, 9204.
Mullagulova, A.; Shaimardanova, A.; Solovyeva, V.; Mukhamedshina, Y.; Chulpanova, D.; Kostennikov, A.; Issa, S.; Rizvanov, A. Safety and Efficacy of Intravenous and Intrathecal Delivery of AAV9-Mediated ARSA in Minipigs. Int. J. Mol. Sci.2023, 24, 9204.
Mullagulova, A.; Shaimardanova, A.; Solovyeva, V.; Mukhamedshina, Y.; Chulpanova, D.; Kostennikov, A.; Issa, S.; Rizvanov, A. Safety and Efficacy of Intravenous and Intrathecal Delivery of AAV9-Mediated ARSA in Minipigs. Int. J. Mol. Sci. 2023, 24, 9204.
Abstract
Metachromatic leukodystrophy (MLD) is a hereditary neurodegenerative disease characterized by demye-lination and motor and cognitive impairment due to the deficiency of the lysosomal enzyme arylsulfatase A (ARSA) or the saposin B activator protein (SapB). Current treatments are limited; however, gene therapy using adeno-associated virus (AAV) vectors for ARSA delivery has shown promising results. The main challenges for MLD gene therapy include optimizing AAV dosage, selecting the most effective serotype, and determining the best route of administration for ARSA delivery into the central nervous system. This study aims to evaluate the safety and efficacy of AAV serotype 9 encoding ARSA (AAV9-ARSA) gene therapy when administered intrave-nously or intrathecally in minipigs, a large animal model with anatomical and physiological similarities to humans. By comparing these two administration methods, this study contributes to the understanding of how to improve the effectiveness of MLD gene therapy and offers valuable insights for future clinical applications.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
,
*
