Advances in Gene Therapy for Muscular Dystrophies

Overview

Journal F1000Res

Specialties Biomedical Engineering
Science

Date 2016 Sep 6

PMID 27594988

Citations 9

Authors

Hayder Abdul-Razak

Alberto Malerba

George Dickson

Affiliations

Soon will be listed here.

Abstract

Duchenne muscular dystrophy (DMD) is a recessive lethal inherited muscular dystrophy caused by mutations in the gene encoding dystrophin, a protein required for muscle fibre integrity. So far, many approaches have been tested from the traditional gene addition to newer advanced approaches based on manipulation of the cellular machinery either at the gene transcription, mRNA processing or translation levels. Unfortunately, despite all these efforts, no efficient treatments for DMD are currently available. In this review, we highlight the most advanced therapeutic strategies under investigation as potential DMD treatments.

Citing Articles

Gene Therapy for Duchenne Muscular Dystrophy.

Elangkovan N, Dickson G J Neuromuscul Dis. 2021; 8(s2):S303-S316.

PMID: 34511510 PMC: 8673537. DOI: 10.3233/JND-210678.

Population-Wide Duchenne Muscular Dystrophy Carrier Detection by CK and Molecular Testing.

Han S, Xu H, Zheng J, Sun J, Feng X, Wang Y Biomed Res Int. 2020; 2020:8396429.

PMID: 33029525 PMC: 7537677. DOI: 10.1155/2020/8396429.

Duchenne muscular dystrophy animal models for high-throughput drug discovery and precision medicine.

Wasala N, Chen S, Duan D Expert Opin Drug Discov. 2020; 15(4):443-456.

PMID: 32000537 PMC: 7065965. DOI: 10.1080/17460441.2020.1718100.

Peptide-conjugate antisense based splice-correction for Duchenne muscular dystrophy and other neuromuscular diseases.

Tsoumpra M, Fukumoto S, Matsumoto T, Takeda S, Wood M, Aoki Y EBioMedicine. 2019; 45:630-645.

PMID: 31257147 PMC: 6642283. DOI: 10.1016/j.ebiom.2019.06.036.

Human induced pluripotent stem cell models for the study and treatment of Duchenne and Becker muscular dystrophies.

Piga D, Salani S, Magri F, Brusa R, Mauri E, Comi G Ther Adv Neurol Disord. 2019; 12:1756286419833478.

PMID: 31105767 PMC: 6501480. DOI: 10.1177/1756286419833478.

References

Aartsma-Rus A, Fokkema I, Verschuuren J, Ginjaar I, van Deutekom J, van Ommen G . Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations. Hum Mutat. 2009; 30(3):293-9. DOI: 10.1002/humu.20918. View

Ramos J, Chamberlain J . Gene Therapy for Duchenne muscular dystrophy. Expert Opin Orphan Drugs. 2015; 3(11):1255-1266. PMC: 4651452. DOI: 10.1517/21678707.2015.1088780. View

Gao X, Shen X, Dong X, Ran N, Han G, Cao L . Peptide Nucleic Acid Promotes Systemic Dystrophin Expression and Functional Rescue in Dystrophin-deficient mdx Mice. Mol Ther Nucleic Acids. 2015; 4:e255. PMC: 4881755. DOI: 10.1038/mtna.2015.27. View

Hodgkinson L, Sorbera L, Graul A . Duchenne muscular dystrophy drugs face tough path to approval. Drugs Today (Barc). 2016; 52(3):199-202. DOI: 10.1358/dot.2016.52.3.2473590. View

Ousterout D, Perez-Pinera P, Thakore P, Kabadi A, Brown M, Qin X . Reading frame correction by targeted genome editing restores dystrophin expression in cells from Duchenne muscular dystrophy patients. Mol Ther. 2013; 21(9):1718-26. PMC: 3776627. DOI: 10.1038/mt.2013.111. View

Nelson C, Hakim C, Ousterout D, Thakore P, Moreb E, Castellanos Rivera R . In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science. 2016; 351(6271):403-7. PMC: 4883596. DOI: 10.1126/science.aad5143. View

Lu-Nguyen N, Jarmin S, Saleh A, Popplewell L, Gait M, Dickson G . Combination Antisense Treatment for Destructive Exon Skipping of Myostatin and Open Reading Frame Rescue of Dystrophin in Neonatal mdx Mice. Mol Ther. 2015; 23(8):1341-1348. PMC: 4579549. DOI: 10.1038/mt.2015.88. View

Cox G, Kunkel L . Dystrophies and heart disease. Curr Opin Cardiol. 1997; 12(3):329-43. View

Vulin A, Barthelemy I, Goyenvalle A, Thibaud J, Beley C, Griffith G . Muscle function recovery in golden retriever muscular dystrophy after AAV1-U7 exon skipping. Mol Ther. 2012; 20(11):2120-33. PMC: 3498802. DOI: 10.1038/mt.2012.181. View

10.

Neri M, Torelli S, Brown S, Ugo I, Sabatelli P, Merlini L . Dystrophin levels as low as 30% are sufficient to avoid muscular dystrophy in the human. Neuromuscul Disord. 2007; 17(11-12):913-8. DOI: 10.1016/j.nmd.2007.07.005. View

11.

Cavazzana-Calvo M, Fischer A . Gene therapy for severe combined immunodeficiency: are we there yet?. J Clin Invest. 2007; 117(6):1456-65. PMC: 1878528. DOI: 10.1172/JCI30953. View

12.

Blankinship M, Gregorevic P, Chamberlain J . Gene therapy strategies for Duchenne muscular dystrophy utilizing recombinant adeno-associated virus vectors. Mol Ther. 2005; 13(2):241-9. DOI: 10.1016/j.ymthe.2005.11.001. View

13.

Maggio I, Stefanucci L, Janssen J, Liu J, Chen X, Mouly V . Selection-free gene repair after adenoviral vector transduction of designer nucleases: rescue of dystrophin synthesis in DMD muscle cell populations. Nucleic Acids Res. 2016; 44(3):1449-70. PMC: 4756843. DOI: 10.1093/nar/gkv1540. View

14.

Mendell J, Rodino-Klapac L, Sahenk Z, Roush K, Bird L, Lowes L . Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol. 2013; 74(5):637-47. DOI: 10.1002/ana.23982. View

15.

Muntoni F, Wood M . Targeting RNA to treat neuromuscular disease. Nat Rev Drug Discov. 2011; 10(8):621-37. DOI: 10.1038/nrd3459. View

16.

Long C, McAnally J, Shelton J, Mireault A, Bassel-Duby R, Olson E . Prevention of muscular dystrophy in mice by CRISPR/Cas9-mediated editing of germline DNA. Science. 2014; 345(6201):1184-1188. PMC: 4398027. DOI: 10.1126/science.1254445. View

17.

Koo T, Popplewell L, Athanasopoulos T, Dickson G . Triple trans-splicing adeno-associated virus vectors capable of transferring the coding sequence for full-length dystrophin protein into dystrophic mice. Hum Gene Ther. 2013; 25(2):98-108. DOI: 10.1089/hum.2013.164. View

18.

Benabdallah B, Duval A, Rousseau J, Chapdelaine P, Holmes M, Haddad E . Targeted Gene Addition of Microdystrophin in Mice Skeletal Muscle via Human Myoblast Transplantation. Mol Ther Nucleic Acids. 2013; 2:e68. PMC: 3564421. DOI: 10.1038/mtna.2012.55. View

19.

Kinali M, Arechavala-Gomeza V, Feng L, Cirak S, Hunt D, Adkin C . Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study. Lancet Neurol. 2009; 8(10):918-28. PMC: 2755039. DOI: 10.1016/S1474-4422(09)70211-X. View

20.

Bladen C, Salgado D, Monges S, Foncuberta M, Kekou K, Kosma K . The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations. Hum Mutat. 2015; 36(4):395-402. PMC: 4405042. DOI: 10.1002/humu.22758. View