AAV1.NT-3 gene therapy for X-linked Charcot-Marie-Tooth neuropathy type 1.

Autor: Ozes B; Center for Gene Therapy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA., Myers M; Center for Gene Therapy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA., Moss K; Center for Gene Therapy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA., Mckinney J; Department of Pediatrics and Neurology, Nationwide Children's Hospital and The Ohio State University, Columbus, OH, USA., Ridgley A; Center for Gene Therapy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA., Chen L; Center for Gene Therapy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA., Bai S; Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, OH, USA.; Biostatistics Resource at Nationwide Children's Hospital, Columbus, OH, USA., Abrams CK; Department of Neurology and Rehabilitation, University of Illinois at Chicago, Chicago, IL, USA., Freidin MM; Department of Neurology and Rehabilitation, University of Illinois at Chicago, Chicago, IL, USA., Mendell JR; Center for Gene Therapy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.; Department of Pediatrics and Neurology, Nationwide Children's Hospital and The Ohio State University, Columbus, OH, USA., Sahenk Z; Center for Gene Therapy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA. zarife.sahenk@nationwidechildrens.org.; Department of Pediatrics and Neurology, Nationwide Children's Hospital and The Ohio State University, Columbus, OH, USA. zarife.sahenk@nationwidechildrens.org.; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA. zarife.sahenk@nationwidechildrens.org.
Jazyk: angličtina
Zdroj: Gene therapy [Gene Ther] 2022 Apr; Vol. 29 (3-4), pp. 127-137. Date of Electronic Publication: 2021 Feb 04.
DOI: 10.1038/s41434-021-00231-3
Abstrakt: X-linked Charcot-Marie-Tooth neuropathy (CMTX) is caused by mutations in the gene encoding Gap Junction Protein Beta-1 (GJB1)/Connexin32 (Cx32) in Schwann cells. Neurotrophin-3 (NT-3) is an important autocrine factor supporting Schwann cell survival and differentiation and stimulating axon regeneration and myelination. Improvements in these parameters have been shown previously in a CMT1 model, Trembler J mouse, with NT-3 gene transfer therapy. For this study, scAAV1.tMCK.NT-3 was delivered to the gastrocnemius muscle of 3-month-old Cx32 knockout (KO) mice. Measurable levels of NT-3 were found in the serum at 6-month post gene delivery. The outcome measures included functional, electrophysiological and histological assessments. At 9-months of age, NT-3 treated mice showed no functional decline with normalized compound muscle action potential amplitudes. Myelin thickness and nerve conduction velocity significantly improved compared with untreated cohort. A normalization toward age-matched wildtype histopathological parameters included increased number of Schmidt-Lanterman incisures, and muscle fiber diameter. Collectively, these findings suggest a translational application to CMTX1.
(© 2021. The Author(s).)
Databáze: MEDLINE
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