Dystrophin and Beyond: A Review of Genetic Landscape of Duchenne Muscular Dystrophy
Article Sidebar
Main Article Content
Abstract
Duchenne muscular dystrophy (DMD) is a very severe, progressive, and lethal disease of skeletal muscle degeneration, respiratory complications, and cardiomyopathy. The identification of the dystrophin gene requires an understanding of the muscle protein and its working mechanism. The learnings from decades of research in life sciences could establish the functionalities of dystrophin in striated muscle. Here, we discuss the pathophysiological basis and the recent advancement of DMD towards the therapeutic approaches that are currently close to or are under ongoing clinical trials in humans. We attempted to summarise the current understanding of DMD – the dystrophin glycoprotein complex and chronic inflammation. Understanding the complex pathophysiology of DMD is crucial for the development of effective treatment and adds hope to the ongoing experimental research.
Downloads
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
How to Cite
References
Johns Hopkins Medicine, Duchenne Muscular Dystrophy, https://www.hopkinsmedicine.org/health/conditions-and-diseases/duchenne-muscular-dystrophy
Farrar MA, Kariyawasam D, Grattan S, Bayley K, Davis M, Holland S, Waddel LB, Jones K, Lorentzos M, Ravine A, Wotton T, Wiley V; DMD NBS Working Group. Newborn Screening for the Diagnosis and Treatment of Duchenne Muscular Dystrophy. J Neuromuscul Dis. 2023;10(1):15-28. PMID: 36373292; PMCID: PMC9881031. DOI: https://doi.org/10.3233/JND-221535
Isela C. Valera, Amanda L. Wacker, Hyun Seok Hwang, Christina Holmes, Orlando Laitano, Andrew P. Landstrom, Michelle S. Parvatiyar, Essential roles of the dystrophin-glycoprotein complex in different cardiac pathologies, Advances in Medical Sciences, Volume 66, Issue 1, 2021, Pages 52-71, ISSN 1896-1126, DOI: https://doi.org/10.1016/j.advms.2020.12.004
Gruber D, Lloyd-Puryear M, Armstrong N, Scavina M, Tavakoli NP, Brower AM, Caggana M, Chung WK. Newborn screening for Duchenne muscular dystrophy: early detection and diagnostic algorithm for female carriers of Duchenne muscular dystrophy. Am J Med Genet C Semin Med Genet. 2022 Jun;190(2):197-205. Epub 2022 Sep 24. PMID: 36152336; PMCID: PMC9826042.
DOI: https://doi.org/10.1002/ajmg.c.32000
Valera IC, Wacker AL, Hwang HS, Holmes C, Laitano O, Landstrom AP, Parvatiyar MS. Essential roles of the dystrophin-glycoprotein complex in different cardiac pathologies. Adv Med Sci. 2021 Mar;66(1):52-71. Epub 2020 Dec 30. PMID: 33387942.
DOI: https://doi.org/10.1016/j.advms.2020.12.004
Bez Batti Angulski A, Hosny N, Cohen H, Martin AA, Hahn D, Bauer J, Metzger JM. Duchenne muscular dystrophy: disease mechanism and therapeutic strategies. Front Physiol. 2023 Jun 26;14:1183101. PMID: 37435300; PMCID: PMC10330733.
DOI: https://doi.org/10.3389/fphys.2023.1183101
Bez Batti Angulski A, Hosny N, Cohen H, Martin AA, Hahn D, Bauer J, Metzger JM. Duchenne muscular dystrophy: disease mechanism and therapeutic strategies. Front Physiol. 2023 Jun 26;14:1183101. PMID: 37435300; PMCID: PMC10330733.
DOI: https://doi.org/10.3389/fphys.2023.1183101
Duan D. Micro-Dystrophin Gene Therapy Goes Systemic in Duchenne Muscular Dystrophy Patients. Hum Gene Ther. 2018 Jul;29(7):733-736. Epub 2018 Apr 5. PMID: 29463117; PMCID: PMC6066190. DOI: https://doi.org/10.1089/hum.2018.012
Zhao J, Kodippili K, Yue Y, Hakim CH, Wasala L, Pan X, Zhang K, Yang NN, Duan D, Lai Y. Dystrophin contains multiple independent membrane-binding domains. Hum Mol Genet. 2016 Sep 1;25(17):3647-3653. Epub 2016 Jul 4. PMID: 27378693; PMCID: PMC5216612. DOI: https://doi.org/10.1093/hmg/ddw210
The importance of dystrophin and the dystrophin-associated proteins in vascular smooth muscle Katherine M. Kaplan, Kathleen G. Morgan, Department of Health Sciences, Molecular Biology, Cell Biology & Biochemistry Program, Boston University, Boston, MA, United States. DOI:https://doi.org/10.3389/fphys.2022.1059021
Niks, E. H., & Aartsma-Rus, A. (2016). Exon Skipping: A First-in-Class Strategy for Duchenne Muscular Dystrophy. Expert Opinion on Biological Therapy, 17(2), 225–236.DOI: https://doi.org/10.1080/14712598.2017.1271872
Łoboda A, Dulak J. Muscle and cardiac therapeutic strategies for Duchenne muscular dystrophy: past, present, and future. Pharmacol Rep. 2020 Oct;72(5):1227-1263. Epub 2020 Jul 20. PMID: 32691346; PMCID: PMC7550322. DOI: https://doi.org/10.1007/s43440-020-00134-x
Holmes, L.; LaHurd, A.; Wasson, E.; McClarin, L.; Dabney, K. Racial and Ethnic Heterogeneity in the Association Between Total Cholesterol and Pediatric Obesity. Int. J. Environ. Res. Public Health 2016, 13, 19 (article number: 19). DOI: https://doi.org/10.3390/ijerph13010019
Wörner, T.P., Bennett, A., Habka, S. et al. Adeno-associated virus capsid assembly is divergent and stochastic. Nat Commun 12, 1642 (2021). DOI: https://doi.org/10.1038/s41467-021-21935-5
Buclez PO, Dias Florencio G, Relizani K, Beley C, Garcia L, Benchaouir R. Rapid, scalable, and low-cost purification of recombinant adeno-associated virus produced by baculovirus expression vector system. Mol Ther Methods Clin Dev. 2016 May 11; 3:16035. PMID: 27226971; PMCID: PMC4867670. DOI: https://doi.org/10.1038/mtm.2016.35
Zheng Z, Ye J, Leng M, Gan C, Tang N, Li W, Valencia CA, Dong B, Chow HY. Enhanced sensitivity of neutralizing antibody detection for different AAV serotypes using HeLa cells with overexpressed AAVR. Front Pharmacol. 2023 Apr 27; 14:1188290. PMID: 37188274; PMCID: PMC10176094. DOI: https://doi.org/10.3389/fphar.2023.1188290
Junyu Yan, Ziqian Li, Yue Shu, Hui Chen, Tianxingzi Wang, Xin Li, Yuhang Zhang, LiLi Li, Yuntao Zhang, The Unveiled Novel regulator of Adeno-associated virus production in HEK293 cells, Gene, Volume 938,2025,149122, ISSN 0378-1119,
DOI: https://doi.org/10.1016/j.gene.2024.149122
Wang, JH., Gessler, D.J., Zhan, W. et al. Adeno-associated virus as a delivery vector for gene therapy of human diseases. Sig Transduct Target Ther 9, 78 (2024). DOI: https://doi.org/10.1038/s41392-024-01780-w
Long C, Li H, Tiburcy M, Rodriguez-Caycedo C, Kyrychenko V, Zhou H, Zhang Y, Min YL, Shelton JM, Mammen PPA, Liaw NY, Zimmermann WH, Bassel-Duby R, Schneider JW, Olson EN. Correction of diverse muscular dystrophy mutations in human engineered heart muscle by single-site genome editing. Sci Adv. 2018 Jan 31;4(1):eaap9004. PMID: 29404407; PMCID: PMC5796795. DOI: https://doi.org/10.1126/sciadv.aap9004
Farrar MA, Kariyawasam D, Grattan S, Bayley K, Davis M, Holland S, Waddel LB, Jones K, Lorentzos M, Ravine A, Wotton T, Wiley V; DMD NBS Working Group. Newborn Screening for the Diagnosis and Treatment of Duchenne Muscular Dystrophy. J Neuromuscul Dis. 2023;10(1):15-28. PMID: 36373292; PMCID: PMC9881031. DOI: https://doi.org/10.3233/JND-221535
NHS. Macular Dystrophy, https://www.nhs.uk/conditions/muscular-dystrophy/genetic-tests/
Everylife Foundation of rare disease, https://everylifefoundation.org/newborn-screening-take-action/newborn-screening-duchenne-muscular-dystrophy/
Everylife Foundation of rare disease, https://everylifefoundation.org/newborn-screening-take-action/newborn-screening-duche/
What is CRISPR-Cas9, and how does it work?. https://www.yourgenome.org/theme/what-is-crispr-cas9/
Written by Anina Werner 18. October 2022, https://www.integra-biosciences.com/united-states/en/blog/article/what-crispr-cas9-and-how-does-it-work
What are genome editing and CRISPR-Cas9? Medlineplus https://medlineplus.gov/genetics/understanding/genomicresearch/genomeediting/
Mercuri E, Bönnemann CG, Muntoni F. Muscular dystrophies. Lancet. 2019 Nov 30;394(10213):2025-2038. PMID: 31789220.
DOI: https://doi.org/10.1016/S0140-6736(19)32910-1
The importance of dystrophin and the dystrophin-associated proteins in vascular smooth muscle Katherine M. Kaplan, Kathleen G. Morgan, Department of Health Sciences, Molecular Biology, Cell Biology & Biochemistry Program, Boston University, Boston, MA, United States DOI: https://doi.org/10.3389/fphys.2022.1059021
Politano L. Read-through approach for stop mutations in Duchenne muscular dystrophy. An update. Acta Myol. 2021 Mar 31;40(1):43-50. PMID: 33870095; PMCID: PMC8033424. DOI:https://doi.org/10.36185/2532-1900-041
Politano, Luisa. (2021). Read-through approach for stop mutations in Duchenne muscular dystrophy. An update. Acta myologica: myopathies and cardiomyopathies: official journal of the Mediterranean Society of Myology. 40.
-50. DOI: https://doi.org/10.36185/2532-1900-041