Gene Therapies That Restore Dystrophin Expression for the Treatment of Duchenne Muscular Dystrophy

Overview

Journal Hum Genet

Specialty Genetics

Date 2016 Aug 21

PMID 27542949

Citations 24

Authors

Jacqueline N Robinson-Hamm

Charles A Gersbach

Affiliations

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Abstract

Duchenne muscular dystrophy is one of the most common inherited genetic diseases and is caused by mutations to the DMD gene that encodes the dystrophin protein. Recent advances in genome editing and gene therapy offer hope for the development of potential therapeutics. Truncated versions of the DMD gene can be delivered to the affected tissues with viral vectors and show promising results in a variety of animal models. Genome editing with the CRISPR/Cas9 system has recently been used to restore dystrophin expression by deleting one or more exons of the DMD gene in patient cells and in a mouse model that led to functional improvement of muscle strength. Exon skipping with oligonucleotides has been successful in several animal models and evaluated in multiple clinical trials. Next-generation oligonucleotide formulations offer significant promise to build on these results. All these approaches to restoring dystrophin expression are encouraging, but many hurdles remain. This review summarizes the current state of these technologies and summarizes considerations for their future development.

Citing Articles

Pharmacological Treatments and Therapeutic Targets in Muscle Dystrophies Generated by Alterations in Dystrophin-Associated Proteins.

Luna-Angulo A, Landa-Solis C, Escobar-Cedillo R, Estrada-Mena F, Sanchez-Chapul L, Gomez-Diaz B Medicina (Kaunas). 2024; 60(7).

PMID: 39064489 PMC: 11279157. DOI: 10.3390/medicina60071060.

Respiratory characterization of a humanized Duchenne muscular dystrophy mouse model.

Roger A, Biswas D, Huston M, Le D, Bailey A, Pucci L Respir Physiol Neurobiol. 2024; 326:104282.

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Case Report: Identification of Maternal Low-Level Mosaicism in the Dystrophin Gene by Droplet Digital Polymerase Chain Reaction.

Jin P, Gao X, Wang M, Qian Y, Yang J, Yang Y Front Genet. 2021; 12:686993.

PMID: 34276787 PMC: 8280780. DOI: 10.3389/fgene.2021.686993.

Heterogenetic parabiosis between healthy and dystrophic mice improve the histopathology in muscular dystrophy.

Lu A, Guo P, Wang L, Tseng C, Huard M, Allen C Sci Rep. 2020; 10(1):7075.

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Comparative proteomic analyses of Duchenne muscular dystrophy and Becker muscular dystrophy muscles: changes contributing to preserve muscle function in Becker muscular dystrophy patients.

Capitanio D, Moriggi M, Torretta E, Barbacini P, De Palma S, Vigano A J Cachexia Sarcopenia Muscle. 2020; 11(2):547-563.

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