Safety, efficacy, and distal nerve Schwann cell biodistribution in mice and NHPs to support translation of AAV9 RNAi therapy for CMT1A

Molecular Therapy — Nucleic Acids 2026 Open access

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Authors: Marina Stavrou, Lindsay M. Wallace, Merlin P. Thangaraj, Noah K. Taylor, Alexia Kagiava, Revekka Papacharalambous, Cynthia McAllister, Gloria Zender, Nizar Y. Saad, M. Bilal Bayazit, Amanda Heslegrave, Christina Tryfonos
+6 more Jan Richter, Henrik Zetterberg, Brian Price, Rachel Salzman, Kleopas A. Kleopa, Scott Q. Harper
DOI: 10.1016/j.omtn.2026.102881
Cited by: 2
References: 44

Abstract

, identified a safe and effective dosing range in mice, demonstrated absence of significant toxicity in rodents and non-human primates (NHPs), and performed a detailed AAV biodistribution study in a large animal model. We found vector biodistribution and miR871 expression in distal peripheral nerves, PMP22 target engagement in mice and NHPs, and silencing to levels expected to support normal myelination in humans. We identified the minimally efficacious to maximum tolerated dose range of AAV9.U6.miR871 in mice and confirmed safety range in NHPs for extrapolation to anticipated clinical trials. Our study supports the scale-up potential of gene therapy to treat CMT1A and other demyelinating peripheral neuropathies.

Fields of Study & Subjects

Nerve injury and regeneration Hereditary Neurological Disorders Neurogenetic and Muscular Disorders Research

Publication details

Journal / source
Molecular Therapy — Nucleic Acids
Publisher
Elsevier BV
Volume
37
Issue
2
Pages
102881–102881
Publication date
27 February 2026
Language
EN