Document Type

Article

Publication Date

9-10-2026

Keywords

Dystrophy, Myopathy, muscle, gene therapy, phospholipid, phosphatidylcholine, choline kinase, CHKB

Abstract

Loss-of-function variants of the CHKB gene cause an autosomal recessive disease described as an early onset congenital megaconial (large peripheral mitochondria) muscular dystrophy. CHKB encodes choline kinase β, the first enzyme in the biochemical pathway for synthesis of the major membrane phospholipid phosphatidylcholine. Chkb-/- mice recapitulate the human disease with affected skeletal muscle displaying a decrease in strength, myofiber atrophy, megaconial mitochondria, fat accumulation within muscle cells, and an increase in muscle injury. Here, we assessed the therapeutic potential of an AAV therapy for the treatment of CHKB-mediated muscular dystrophy. Chkb-/- mice were injected once suborbitally with three different doses of recombinant AAV9 (rAAV9) encoding human CHKB under control of a constitutive and ubiquitous promoter (AAV9-CHKB). The AAV9-CHKB-treated mice were biochemically and phenotypically indistinguishable from the wild type mice. In the Chkb-/- mouse model, all doses resulted in expression of the CHKB protein and restored choline kinase β enzyme activity, body and muscle weight, and normal muscle cell physiology, and they prevented lipid metabolism imbalance and increased the capacity to walk. These findings point to AAV9-mediated gene therapy as a potential treatment for CHKB-mediated disease.

Comments

10.1016/j.omta.2026.201766

Publisher Attribution

Molecular Therapy: Advances Vol. 34 September 2026 © 2026 The Author(s). Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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