Duchenne muscular dystrophy

File:Drawing of boy with Duchenne muscular dystrophy.png

Duchenne muscular dystrophy causes progressive muscle weakness due to muscle fiber disarray, death, and replacement with connective tissue or fat. The voluntary muscles are affected first, especially those of the hips, pelvic area, thighs, calves.{{cite web |url=https://rarediseases.info.nih.gov/diseases/6291/duchenne-muscular-dystrophy |access-date=24 January 2021 |title=Duchenne muscular dystrophy |website=Genetic and Rare Diseases (GARD) Information Center |archive-date=23 November 2016 |archive-url=https://web.archive.org/web/20161123090800/https://rarediseases.info.nih.gov/diseases/6291/duchenne-muscular-dystrophy |url-status=live}} {{PD-notice}} It eventually progresses to the shoulders and neck, followed by arms, respiratory muscles, and other areas. Fatigue is common.{{cite journal |vauthors=Angelini C, Tasca E |title=Fatigue in muscular dystrophies |journal=Neuromuscular Disorders |volume=22 |pages=S214–S220 |date=December 2012 |issue=Suppl 3 |pmid=23182642 |pmc=3526799 |doi=10.1016/j.nmd.2012.10.010 |doi-access=free |title-link=doi}}

Signs usually appear before age five, and may even be observed when a boy takes his first steps.{{cite book | vauthors = Rowland LP | date = 1985 | chapter = Clinical Perspective: Phenotypic Expression In Muscular Dystrophy | veditors = Strohman C, Wolf S | title = Gene Expression in Muscle | series = Advances in Experimental Medicine and Biology | pages = 3–5 | publisher = Plenum Press | chapter-url = https://www.springer.com/gp/book/9781468449099 | isbn = 978-1-4684-4907-5 | access-date = 7 August 2019 | archive-date = 29 September 2020 | archive-url = https://web.archive.org/web/20200929152544/https://www.springer.com/gp/book/9781468449099 | url-status = live }} There is general difficulty with motor skills, which can result in an awkward manner of walking, stepping, or running. They tend to walk on their toes, in part due to shortening of the Achilles tendon,{{cite book |vauthors=Emery AE, Muntoni F, Quinlivan R |title=Duchenne Muscular Dystrophy |date=2015 |publisher=OUP Oxford |isbn=978-0-19968148-8 |edition=Fourth |url=https://books.google.com/books?id=iFPCBwAAQBAJ&pg=PP1 |access-date=27 May 2020 |archive-date=31 March 2024 |archive-url=https://web.archive.org/web/20240331202526/https://books.google.com/books?id=iFPCBwAAQBAJ&pg=PP1#v=onepage&q&f=false |url-status=live }} and because it compensates for knee extensor weakness. Falls can be frequent. It becomes increasingly difficult for the boy to walk. The ability to walk usually disintegrates completely before age 13. Most men affected with Duchenne muscular dystrophy become essentially "paralyzed from the neck down" by the age of 21. Cardiomyopathy, particularly dilated cardiomyopathy, is common, seen in half of 18-year-olds.{{cite book | vauthors = Darras BT, Urion DK, Ghosh PS | chapter = Dystrophinopathies | title = GeneReviews | location = Seattle (WA) | publisher = University of Washington | date = 2018 | pmid = 20301298 }} The development of congestive heart failure or arrhythmia (irregular heartbeat) is only occasional. In late stages of the disease, respiratory impairment and swallowing impairment can occur, which can result in pneumonia.{{MedlinePlusEncyclopedia|000705|Duchenne muscular dystrophy}}

File:Gowers's sign.png

A classic sign of Duchenne muscular dystrophy is trouble getting up from a lying or sitting position,{{cite web |url=http://www.mayoclinic.org/diseases-conditions/muscular-dystrophy/basics/symptoms/con-20021240 |title=Muscular dystrophy - Symptoms and causes |website=Mayo Clinic |access-date=6 February 2015 |url-status=live |archive-url=https://web.archive.org/web/20150206164411/http://www.mayoclinic.org/diseases-conditions/muscular-dystrophy/basics/symptoms/con-20021240 |archive-date=6 February 2015 }} as manifested by a positive Gowers's sign. When a child tries to rise from lying on his stomach, he compensates for pelvic muscle weakness through the use of the upper extremities: first by rising to stand on his arms and knees, and then "walking" his hands up his legs to stand upright. Another characteristic sign of Duchenne muscular dystrophy is pseudohypertrophy (enlarging) of the muscles of the tongue, calves, buttocks, and shoulders (around age 4 or 5). Fat and connective tissue eventually replace the muscle tissue, hence the term pseudohypertrophy. Muscle fiber deformities and muscle contractures of Achilles tendon and hamstrings can occur, which impair functionality because the muscle fibers shorten and fibrose in connective tissue. Skeletal deformities can occur, such as lumbar hyperlordosis, scoliosis, anterior pelvic tilt, and chest deformities. Lumbar hyperlordosis is thought to be a compensatory mechanism in response to gluteal and quadriceps muscle weakness, all of which cause altered posture and gait (e.g.: restricted hip extension).{{cite journal | vauthors = Sutherland DH, Olshen R, Cooper L, Wyatt M, Leach J, Mubarak S, Schultz P | title = The pathomechanics of gait in Duchenne muscular dystrophy | journal = Developmental Medicine and Child Neurology | volume = 23 | issue = 1 | pages = 3–22 | date = February 1981 | pmid = 7202868 | doi = 10.1111/j.1469-8749.1981.tb08442.x | s2cid = 895379 }}{{cite journal | vauthors = Baptista CR, Costa AA, Pizzato TM, Souza FB, Mattiello-Sverzut AC | title = Postural alignment in children with Duchenne muscular dystrophy and its relationship with balance | journal = Brazilian Journal of Physical Therapy | volume = 18 | issue = 2 | pages = 119–126 | date = 2014 | pmid = 24838810 | pmc = 4183248 | doi = 10.1590/s1413-35552012005000152 }}

Non-musculoskeletal manifestations of Duchenne muscular dystrophy occur. There is a higher risk of neurobehavioral disorders (e.g., ADHD), learning disorders (dyslexia), and non-progressive weaknesses in specific cognitive skills (in particular short-term verbal memory), which are believed to be the result of inadequate dystrophin in the brain.{{cite journal | vauthors = Doorenweerd N, Mahfouz A, van Putten M, Kaliyaperumal R, T' Hoen PA, Hendriksen JG, Aartsma-Rus AM, Verschuuren JJ, Niks EH, Reinders MJ, Kan HE, Lelieveldt BP | title = Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy | journal = Scientific Reports | volume = 7 | issue = 1 | page = 12575 | date = October 2017 | pmid = 28974727 | pmc = 5626779 | doi = 10.1038/s41598-017-12981-5 | bibcode = 2017NatSR...712575D }}

Image:X-linked recessive.svg

Duchenne muscular dystrophy is caused by a mutation of the dystrophin gene, located on the short arm of the X chromosome (locus Xp21){{OMIM|310200|Muscular Dystrophy, Duchenne Type; DMD}} that codes for dystrophin protein. Mutations can either be inherited or occur spontaneously during germline transmission,{{citation needed|date=August 2016}} causing a large reduction or absence of dystrophin, a protein that provides structural integrity in muscle cells.{{cite journal | vauthors = Vera CD, Zhang A, Pang PD, Wu JC | title = Treating Duchenne Muscular Dystrophy: The Promise of Stem Cells, Artificial Intelligence, and Multi-Omics | journal = Frontiers in Cardiovascular Medicine | volume = 9 | page = 851491 | date = 2022 | pmid = 35360042 | pmc = 8960141 | doi = 10.3389/fcvm.2022.851491 | doi-access = free | title-link = doi }} Dystrophin is responsible for connecting the actin cytoskeleton of each muscle fiber to the underlying basal lamina (extracellular matrix), through a protein complex containing many subunits. The absence of dystrophin permits excess calcium to penetrate the sarcolemma (the muscle cell membrane).{{cite web|url=http://www.forschungsportal.ch/unibe/abstracts/A_62193673.html |title=Duchenne Muscular Dystrophy: Pathophysiological Implications of Mitochondrial Calcium Signaling and ROS Production |date=2 May 2012 |access-date=29 June 2014 |archive-url=https://web.archive.org/web/20120502165419/http://www.forschungsportal.ch/unibe/abstracts/A_62193673.html |archive-date=2 May 2012 }}

File:Dystrophin diagram.jpg

Duchenne muscular dystrophy is extremely rare in females (about 1 in 50,000,000 female births). It can occur in females with an affected father and a carrier mother, in those who are missing an X chromosome, or in those who have an inactivated X chromosome (the most common of the rare reasons).{{cite web | vauthors=Wahl M | title=Quest - Article - But Girls Don't Get Duchenne, or Do They? - A Quest Article | website=Muscular Dystrophy Association | date=21 October 2016 | url=https://www.mda.org/quest/article/girls-dont-get-duchenne-or-do-they | access-date=6 July 2019 | archive-date=12 April 2019 | archive-url=https://web.archive.org/web/20190412192736/https://www.mda.org/quest/article/girls-dont-get-duchenne-or-do-they | url-status=live }} The daughter of a carrier mother and an affected father will be affected or a carrier with equal probability, as she will always inherit the affected X-chromosome from her father and has a 50% chance of also inheriting the affected X-chromosome from her mother.{{cite web |last=Wucherpfennig |first=Julia |url=https://www.thetech.org/ask-a-geneticist/genetics-duchenne-muscular-dystrophy-dmd/ |title=If a man has Duchenne muscular dystrophy, what are the chances his children will have DMD? |website=The Tech Interactive |series=Ask a Geneticist |date=6 October 2016 |access-date=5 August 2024}}

Disruption of the blood–brain barrier has been seen to be a noted feature in the development of Duchenne muscular dystrophy.{{cite journal | vauthors = Nico B, Ribatti D | title = Morphofunctional aspects of the blood-brain barrier | journal = Current Drug Metabolism | volume = 13 | issue = 1 | pages = 50–60 | date = January 2012 | pmid = 22292807 | doi = 10.2174/138920012798356970 }}

Duchenne muscular dystrophy can be detected with about 95% accuracy by genetic studies performed during pregnancy.

The muscle-specific isoform of the dystrophin gene is composed of 79 exons, and DNA testing (blood test) and analysis can usually identify the specific type of mutation of the exon or exons that are affected. DNA testing confirms the diagnosis in most cases.{{cite web |url=http://www.genome.utah.edu/DMD/methods_abstract.shtml |title=University of Utah Muscular Dystrophy |publisher=Genome.utah.edu |date=28 November 2009 |access-date=16 February 2013 |archive-date=14 September 2003 |archive-url=https://web.archive.org/web/20030914125410/http://www.genome.utah.edu/DMD/methods_abstract.shtml }}

If DNA testing fails to find the mutation, a muscle biopsy test may be performed.{{cite journal | vauthors = Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro F, Tomezsko J, Constantin C | title = Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management | journal = The Lancet. Neurology | volume = 9 | issue = 1 | pages = 77–93 | date = January 2010 | pmid = 19945913 | doi = 10.1016/s1474-4422(09)70271-6 | s2cid = 328499 | citeseerx = 10.1.1.176.4466 }} A small sample of muscle tissue is extracted using a biopsy needle. The key tests performed on the biopsy sample for Duchenne muscular dystrophy are immunohistochemistry, immunocytochemistry, and immunoblotting for dystrophin, and should be interpreted by an experienced neuromuscular pathologist.{{cite journal | vauthors = Nicholson LV, Johnson MA, Bushby KM, Gardner-Medwin D, Curtis A, Ginjaar IB, den Dunnen JT, Welch JL, Butler TJ, Bakker E | title = Integrated study of 100 patients with Xp21 linked muscular dystrophy using clinical, genetic, immunochemical, and histopathological data. Part 2. Correlations within individual patients | journal = Journal of Medical Genetics | volume = 30 | issue = 9 | pages = 737–744 | date = September 1993 | pmid = 8411068 | pmc = 1016530 | doi = 10.1136/jmg.30.9.737 }} These tests provide information on the presence or absence of the protein. Absence of the protein is a positive test for Duchenne muscular dystrophy. Where dystrophin is present, the tests indicate the amount and molecular size of dystrophin, helping to distinguish Duchenne muscular dystrophy from milder dystrophinopathy phenotypes.{{cite journal | vauthors = Muntoni F | title = Is a muscle biopsy in Duchenne dystrophy really necessary? | journal = Neurology | volume = 57 | issue = 4 | pages = 574–575 | date = August 2001 | pmid = 11524463 | doi = 10.1212/wnl.57.4.574 | s2cid = 13474827 }} Over the past several years, DNA tests have been developed that detect more of the many mutations that cause the condition, and muscle biopsy is not required as often to confirm the presence of Duchenne muscular dystrophy.{{cite journal | vauthors = Flanigan KM, von Niederhausern A, Dunn DM, Alder J, Mendell JR, Weiss RB | title = Rapid direct sequence analysis of the dystrophin gene | journal = American Journal of Human Genetics | volume = 72 | issue = 4 | pages = 931–939 | date = April 2003 | pmid = 12632325 | pmc = 1180355 | doi = 10.1086/374176 }}

A prenatal test can be considered when the mother is a known or suspected carrier.{{cite journal | vauthors = Beksac MS, Tanacan A, Aydin Hakli D, Orgul G, Soyak B, Balci Hayta B, Dincer P, Topaloğlu H | title = Gestational Outcomes of Pregnant Women Who Have Had Invasive Prenatal Testing for the Prenatal Diagnosis of Duchenne Muscular Dystrophy | journal = Journal of Pregnancy | volume = 2018 | page = 9718316 | date = 30 July 2018 | pmid = 30151283 | pmc = 6091284 | doi = 10.1155/2018/9718316 | doi-access = free | title-link = doi }}

Before invasive testing, determination of the fetal sex is important; while males are sometimes affected by this X-linked disease, female Duchenne muscular dystrophy is extremely rare. This can be achieved by ultrasound scan at 16 weeks or more recently by free fetal DNA (cffDNA) testing. Chorion villus sampling (CVS) can be done at 11–14 weeks and has a 1% risk of miscarriage. Amniocentesis can be done after 15 weeks and has a 0.5% risk of miscarriage. Non invasive prenatal testing can be done around 10–12 weeks.{{cite journal | vauthors = Devaney SA, Palomaki GE, Scott JA, Bianchi DW | title = Noninvasive fetal sex determination using cell-free fetal DNA: a systematic review and meta-analysis | journal = JAMA | volume = 306 | issue = 6 | pages = 627–636 | date = August 2011 | pmid = 21828326 | pmc = 4526182 | doi = 10.1001/jama.2011.1114 }} Another option in the case of unclear genetic test results is fetal muscle biopsy.{{citation needed|date=November 2023}}

File:Salbutamol.svg (albuterol) — a β₂ agonist]]

No cure for Duchenne muscular dystrophy is known.{{cite web | url=https://www.fda.gov/Drugs/DrugSafety/ucm421270.htm | title=Duchenne Muscular Dystrophy Statement | date=31 October 2014 | publisher=U.S. Food and Drug Administration (FDA) | archive-url=https://web.archive.org/web/20141102003341/https://www.fda.gov/Drugs/DrugSafety/ucm421270.htm | archive-date=2 November 2014 }} {{PD-notice}}

Treatment is generally aimed at controlling symptoms to maximize the quality of life which can be measured using specific questionnaires,{{cite journal |vauthors=Dany A, Barbe C, Rapin A, Réveillère C, Hardouin JB, Morrone I, Wolak-Thierry A, Dramé M, Calmus A, Sacconi S, Bassez G, Tiffreau V, Richard I, Gallais B, Prigent H, Taiar R, Jolly D, Novella JL, Boyer FC |title=Construction of a Quality of Life Questionnaire for slowly progressive neuromuscular disease |journal=Quality of Life Research |volume=24 |issue=11 |pages=2615–2623 |date=November 2015 |pmid=26141500 |doi=10.1007/s11136-015-1013-8 |s2cid=25834947}} and include:

• Corticosteroids such as prednisolone, deflazacort, and Vamorolone (Agamree) lead to short-term improvements in muscle strength and function up to 2 years.{{cite journal |vauthors=Falzarano MS, Scotton C, Passarelli C, Ferlini A |title=Duchenne Muscular Dystrophy: From Diagnosis to Therapy |journal=Molecules |volume=20 |issue=10 |pages=18168–18184 |date=October 2015 |pmid=26457695 |pmc=6332113 |doi=10.3390/molecules201018168 |doi-access=free |title-link=doi}} Corticosteroids have also been reported to help prolong walking, though the evidence for this is not robust.{{cite journal |vauthors=Matthews E, Brassington R, Kuntzer T, Jichi F, Manzur AY |title=Corticosteroids for the treatment of Duchenne muscular dystrophy |journal=The Cochrane Database of Systematic Reviews |volume=5 |issue=5 |pages=CD003725 |date=May 2016 |pmid=27149418 |pmc=8580515 |doi=10.1002/14651858.CD003725.pub4}}
• Disease-specific physical therapy helps maintain muscle strength, flexibility, and function. It aims to:
• Minimize the development of contractures and deformity by developing a program of stretches and exercises where appropriate
• Anticipate and minimize other secondary complications of physical nature by recommending bracing and durable medical equipment{{cite journal |vauthors=Pedlow K, McDonough S, Lennon S, Kerr C, Bradbury I |title=Assisted standing for Duchenne muscular dystrophy |journal=The Cochrane Database of Systematic Reviews |volume=10 |issue=10 |pages=CD011550 |date=October 2019 |pmid=31606891 |pmc=6790222 |doi=10.1002/14651858.CD011550.pub2}}
• Monitor respiratory function and advise on techniques to assist with breathing exercises and methods of clearing secretions{{cite web |title=Duchenne Muscular Dystrophy |url=https://www.physio-pedia.com/Duchenne_Muscular_Dystrophy |access-date=10 October 2022 |website=Physiopedia |archive-date=10 October 2022 |archive-url=https://web.archive.org/web/20221010133739/https://www.physio-pedia.com/Duchenne_Muscular_Dystrophy |url-status=live}}
• Orthopedic appliances (such as braces and wheelchairs) may improve mobility and the ability for self-care. Form-fitting removable leg braces that hold the ankle in place during sleep can defer the onset of contractures.
• Appropriate respiratory support as the disease progresses is important.
• Cardiac problems may require a pacemaker.{{cite journal |vauthors=Verhaert D, Richards K, Rafael-Fortney JA, Raman SV |title=Cardiac involvement in patients with muscular dystrophies: magnetic resonance imaging phenotype and genotypic considerations |journal=Circulation: Cardiovascular Imaging |volume=4 |issue=1 |pages=67–76 |date=January 2011 |pmid=21245364 |pmc=3057042 |doi=10.1161/CIRCIMAGING.110.960740}}

The medication eteplirsen, a Morpholino antisense oligo, has been approved in the United States for the treatment of mutations amenable to dystrophin exon 51 skipping. The US approval has been controversial{{cite journal | title = Railroading at the FDA | journal = Nature Biotechnology | volume = 34 | issue = 11 | page = 1078 | date = November 2016 | pmid = 27824847 | doi = 10.1038/nbt.3733 | doi-access = free | title-link = doi }} as eteplirsen failed to establish a clinical benefit;{{cite press release|title=FDA grants accelerated approval to first drug for Duchenne muscular dystrophy|publisher=U.S. Food and Drug Administration (FDA)|url=https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-first-drug-duchenne-muscular-dystrophy|access-date=8 July 2019|date=19 September 2016|archive-date=2 August 2019|archive-url=https://web.archive.org/web/20190802060217/https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-first-drug-duchenne-muscular-dystrophy|url-status=live}} {{PD-notice}} it has been refused approval by the European Medicines Agency.{{cite web|url=http://www.medscape.com/viewarticle/897496|title=CHMP Advises Against Approval for Eteplirsen in DMD|website=Medscape|access-date=9 July 2019|archive-date=9 July 2019|archive-url=https://web.archive.org/web/20190709081742/http://www.medscape.com/viewarticle/897496|url-status=live}}{{cite web | title=Exondys | website=European Medicines Agency | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/exondys | access-date=3 December 2022 | archive-date=26 November 2020 | archive-url=https://web.archive.org/web/20201126221344/https://www.ema.europa.eu/en/medicines/human/EPAR/exondys | url-status=live }}

The medication ataluren (Translarna) is approved for use in the European Union.{{cite web | title=Translarna EPAR | website=European Medicines Agency (EMA) | date=4 September 2014 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/translarna | access-date=14 August 2020 | archive-date=29 October 2020 | archive-url=https://web.archive.org/web/20201029153952/https://www.ema.europa.eu/en/medicines/human/EPAR/translarna | url-status=live }}{{cite web|title=Translarna - Summary of Product Characteristics (SmPC)|url=https://www.medicines.org.uk/emc/medicine/33294|website=(emc)|access-date=18 June 2017|date=24 April 2017|archive-date=15 July 2017|archive-url=https://web.archive.org/web/20170715082409/http://www.medicines.org.uk/emc/medicine/33294|url-status=live}}

The antisense oligonucleotide golodirsen (Vyondys 53) was approved for medical use in the United States in 2019, for the treatment of cases that can benefit from skipping exon 53 of the dystrophin transcript.{{cite press release | title=FDA grants accelerated approval to first targeted treatment for rare Duchenne muscular dystrophy mutation | publisher=U.S. Food and Drug Administration (FDA) | date=12 December 2019 | url=https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-first-targeted-treatment-rare-duchenne-muscular-dystrophy-mutation | archive-url=https://web.archive.org/web/20191213043443/https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-first-targeted-treatment-rare-duchenne-muscular-dystrophy-mutation | archive-date=13 December 2019 | url-status=live | access-date=12 December 2019}} {{PD-notice}}{{cite web | title=Drug Approval Package: Vyondys 53 (golodirsen) | publisher=U.S. Food and Drug Administration (FDA) | date=21 January 2020 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211970Orig1s000TOC.cfm | access-date=22 January 2020 | archive-date=2 March 2020 | archive-url=https://web.archive.org/web/20200302122445/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211970Orig1s000TOC.cfm | url-status=live }}

The Morpholino antisense oligonucleotide viltolarsen (Viltepso) was approved for medical use in the United States in August 2020, for the treatment of Duchenne muscular dystrophy (DMD) in people who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping.{{cite press release | title=FDA Approves Targeted Treatment for Rare Duchenne Muscular Dystrophy Mutation | publisher=U.S. Food and Drug Administration (FDA) | date=12 August 2020 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-targeted-treatment-rare-duchenne-muscular-dystrophy-mutation | access-date=12 August 2020 | archive-date=20 August 2020 | archive-url=https://web.archive.org/web/20200820041846/https://www.fda.gov/news-events/press-announcements/fda-approves-targeted-treatment-rare-duchenne-muscular-dystrophy-mutation | url-status=live }} {{PD-notice}} Developed by Nippon Shinyaku and the National Center of Neurology and Psychiatry (NCNP), viltolarsen's pre-clinical development was supported by pioneering work from Toshifumi Yokota and colleagues.{{Cite journal |last1=Yokota |first1=Toshifumi |last2=Lu |first2=Qi-Long |last3=Partridge |first3=Terence |last4=Kobayashi |first4=Masanori |last5=Nakamura |first5=Akinori |last6=Takeda |first6=Shińichi |last7=Hoffman |first7=Eric |date=June 2009 |title=Efficacy of systemic morpholino exon-skipping in Duchenne dystrophy dogs |journal=Annals of Neurology |volume=65 |issue=6 |pages=667–676 |doi=10.1002/ana.21627 |issn=1531-8249 |pmc=5951302 |pmid=19288467}} It is the second approved targeted treatment for people with this type of mutation in the United States. Approximately 8% of people with DMD have a mutation that is amenable to exon 53 skipping.

Casimersen (Amondys 45) was approved for medical use in the United States in February 2021,{{cite press release | title=FDA Approves Targeted Treatment for Rare Duchenne Muscular Dystrophy Mutation | publisher=U.S. Food and Drug Administration (FDA) | date=25 February 2021 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-targeted-treatment-rare-duchenne-muscular-dystrophy-mutation-0 | access-date=25 February 2021 | archive-date=3 August 2021 | archive-url=https://web.archive.org/web/20210803155300/https://www.fda.gov/news-events/press-announcements/fda-approves-targeted-treatment-rare-duchenne-muscular-dystrophy-mutation-0 | url-status=live }} {{PD-notice}} and it is the first FDA-approved targeted treatment for people who have a confirmed mutation of the Duchenne muscular dystrophy gene that is amenable to exon 45 skipping.

Comprehensive multidisciplinary care guidelines for Duchenne muscular dystrophy have been developed by the US Centers for Disease Control and Prevention and were published in 2010. An update was published in 2018.{{cite journal | vauthors = Birnkrant DJ, Bushby K, Bann CM, Apkon SD, Blackwell A, Brumbaugh D, Case LE, Clemens PR, Hadjiyannakis S, Pandya S, Street N, Tomezsko J, Wagner KR, Ward LM, Weber DR | title = Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management | journal = The Lancet. Neurology | volume = 17 | issue = 3 | pages = 251–267 | date = March 2018 | pmid = 29395989 | pmc = 5869704 | doi = 10.1016/S1474-4422(18)30024-3 | doi-access = free | title-link = doi }}{{cite journal | vauthors = Birnkrant DJ, Bushby K, Bann CM, Alman BA, Apkon SD, Blackwell A, Case LE, Cripe L, Hadjiyannakis S, Olson AK, Sheehan DW, Bolen J, Weber DR, Ward LM | title = Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management | journal = The Lancet. Neurology | volume = 17 | issue = 4 | pages = 347–361 | date = April 2018 | pmid = 29395990 | pmc = 5889091 | doi = 10.1016/S1474-4422(18)30025-5 | doi-access = free | title-link = doi }}

Delandistrogene moxeparvovec (Elevidys) is a gene therapy that in June 2023 received United States FDA accelerated approval for the treatment of four and five-year-old children.{{cite press release | title=FDA Approves First Gene Therapy for Treatment of Certain Patients with Duchenne Muscular Dystrophy | publisher=U.S. Food and Drug Administration (FDA) | date=22 June 2023 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treatment-certain-patients-duchenne-muscular-dystrophy | access-date=22 June 2023 | archive-date=29 November 2023 | archive-url=https://web.archive.org/web/20231129153732/https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treatment-certain-patients-duchenne-muscular-dystrophy | url-status=live }} {{PD-notice}}{{cite press release | title=Sarepta Therapeutics Announces FDA Approval of Elevidys, the First Gene Therapy to Treat Duchenne Muscular Dystrophy | publisher=Sarepta Therapeutics | via=Business Wire | date=22 June 2023 | url=https://www.businesswire.com/news/home/20230622454844/en/Sarepta-Therapeutics-Announces-FDA-Approval-of-ELEVIDYS-the-First-Gene-Therapy-to-Treat-Duchenne-Muscular-Dystrophy | access-date=22 June 2023 | archive-date=23 June 2023 | archive-url=https://web.archive.org/web/20230623023327/https://www.businesswire.com/news/home/20230622454844/en/Sarepta-Therapeutics-Announces-FDA-Approval-of-ELEVIDYS-the-First-Gene-Therapy-to-Treat-Duchenne-Muscular-Dystrophy | url-status=live }}

In October 2023, the US Food and Drug Administration (FDA) approved Vamorolone (Agamree) as a Treatment for Duchenne muscular dystrophy. Catalyst Pharmaceuticals holds the exclusive North American license and commercial rights.{{cite web |last1=Ciccone |first1=Isabella |title=FDA Approves Vamorolone as a Treatment for Duchenne Muscular Dystrophy |url=https://www.neurologylive.com/view/fda-approves-vamorolone-agamree-duchenne-muscular-dystrophy |website=Neurology Live|date=26 October 2023 }}

In March 2024, the US Food and Drug Administration (FDA) approved givinostat (Duvyzat), an oral medication, to be used in the treatment of Duchenne muscular dystrophy in people aged six years and older. Givinostat is the first nonsteroidal drug to receive FDA approval for the treatment of all genetic variants of Duchenne muscular dystrophy. Functioning as a histone deacetylase (Histone deacetylase (HDAC) inhibitor, givinostat operates by targeting pathogenic processes within the body, ultimately leading to a reduction in inflammation and muscle loss associated with the disease.{{Cite press release |date=21 March 2024 |title=FDA Approves Nonsteroidal Treatment for Duchenne Muscular Dystrophy |url=https://www.fda.gov/news-events/press-announcements/fda-approves-nonsteroidal-treatment-duchenne-muscular-dystrophy |website=U.S. Food and Drug Administration (FDA) |access-date=23 March 2024 |archive-date=23 March 2024 |archive-url=https://web.archive.org/web/20240323061939/https://www.fda.gov/news-events/press-announcements/fda-approves-nonsteroidal-treatment-duchenne-muscular-dystrophy |url-status=live}} {{PD-notice}}

Duchenne muscular dystrophy is a rare progressive disease that eventually affects all voluntary muscles and involves the heart and breathing muscles in later stages. Life expectancy is estimated to be around 25–26,{{cite book |url=https://books.google.com/books?id=BxWOErb3sEgC&pg=PA222 |title=International Neurology |vauthors=Lisak RP, Truong DD, Carroll W, Bhidayasiri R |date=2011 |publisher=Wiley |isbn=978-1-4443-1701-5 |page=222}} but this varies. People born with Duchenne muscular dystrophy after 1990 have a median life expectancy of approximately 28–30.{{cite journal |last1=Broomfield |first1=Jonathan |last2=Hill |first2=Micki |last3=Guglieri |first3=Michela |last4=Crowther |first4=Michael |last5=Abrams |first5=Keith |date=2021-12-07 |title=Life Expectancy in Duchenne Muscular Dystrophy: Reproduced Individual Patient Data Meta-analysis |journal=Neurology |volume=97 |issue=23 |pages=e2304–e2314 |doi=10.1212/WNL.0000000000012910 |issn=0028-3878 |pmid=34645707|pmc=8665435 |doi-access=free}}{{cite journal |last1=Landfeldt |first1=Erik |last2=Thompson |first2=Rachel |last3=Sejersen |first3=Thomas |last4=McMillan |first4=Hugh J. |last5=Kirschner |first5=Janbernd |last6=Lochmüller |first6=Hanns |date=2020 |title=Life expectancy at birth in Duchenne muscular dystrophy: a systematic review and meta-analysis |journal=European Journal of Epidemiology |volume=35 |issue=7 |pages=643–653 |doi=10.1007/s10654-020-00613-8 |issn=1573-7284 |pmc=7387367 |pmid=32107739}} With excellent medical care, affected men often live into their 30s.{{cite web |url=http://www.muscular-dystrophy.org/about_muscular_dystrophy/conditions/97_duchenne_muscular_dystrophy |title=Duchenne muscular dystrophy (DMD) | Muscular Dystrophy Campaign |publisher=Muscular-dystrophy.org |access-date=16 February 2013 |archive-url=https://web.archive.org/web/20130121140345/http://www.muscular-dystrophy.org/about_muscular_dystrophy/conditions/97_duchenne_muscular_dystrophy |archive-date=21 January 2013}} The oldest surviving person in the world with the disease is 60 years old.{{Cite web |last=Medvescek |first=Christina |date=October 31, 2005 |title=Quest - Article - Despite the Challenge, People Love Their Live-Ins |url=https://www.mda.org/quest/article/despite-challenge-people-love-their-live-ins |access-date=2024-10-02 |website=Muscular Dystrophy Association |language=en}}

The most common direct cause of death in people with Duchenne muscular dystrophy is respiratory failure. Complications from treatment, such as mechanical ventilation and tracheotomy procedures, are also a concern. The next leading cause of death is cardiac-related conditions such as heart failure brought on by dilated cardiomyopathy. With respiratory assistance, the median survival age can reach up to 40. In rare cases, people with Duchenne muscular dystrophy have been seen to survive into their forties or early fifties, with proper positioning in wheelchairs and beds, and the use of ventilator support (via tracheostomy or mouthpiece), airway clearance, and heart medications.{{cite journal | vauthors = Kieny P, Chollet S, Delalande P, Le Fort M, Magot A, Pereon Y, Perrouin Verbe B | title = Evolution of life expectancy of patients with Duchenne muscular dystrophy at AFM Yolaine de Kepper centre between 1981 and 2011 | journal = Annals of Physical and Rehabilitation Medicine | volume = 56 | issue = 6 | pages = 443–454 | date = September 2013 | pmid = 23876223 | doi = 10.1016/j.rehab.2013.06.002 | doi-access = free | title-link = doi }} Early planning of the required supports for later-life care has shown greater longevity for people with Duchenne muscular dystrophy.{{cite journal | vauthors = Krajina A, Podrabský P, Steinhart L, Endrys J, Coufal L | title = [Personal experimental experience with the administration of liquid obliterative agents using percutaneous intra-arterial balloon catheters with a controlled leak] | journal = Sbornik Vedeckych Praci Lekarske Fakulty Karlovy Univerzity V Hradci Kralove. Supplementum | volume = 30 | issue = 2 | pages = 201–211 | date = 22 November 2012 | pmid = 3504593 | pmc = 3504593 | doi = 10.1186/1750-1172-7-S2-A8 | doi-access = free | title-link = doi }}

Curiously, in the mdx mouse model of Duchenne muscular dystrophy, the lack of dystrophin is associated with increased calcium levels and skeletal muscle myonecrosis. The intrinsic laryngeal muscles (ILMs) are protected and do not undergo myonecrosis.{{cite journal | vauthors = Marques MJ, Ferretti R, Vomero VU, Minatel E, Neto HS | title = Intrinsic laryngeal muscles are spared from myonecrosis in the mdx mouse model of Duchenne muscular dystrophy | journal = Muscle & Nerve | volume = 35 | issue = 3 | pages = 349–353 | date = March 2007 | pmid = 17143878 | doi = 10.1002/mus.20697 | s2cid = 41968787 }} ILMs have a calcium regulation system profile suggestive of a better ability to handle calcium changes in comparison to other muscles, and this may provide a mechanistic insight for their unique pathophysiological properties.{{cite journal | vauthors = Ferretti R, Marques MJ, Khurana TS, Santo Neto H | title = Expression of calcium-buffering proteins in rat intrinsic laryngeal muscles | journal = Physiological Reports | volume = 3 | issue = 6 | pages = e12409 | date = June 2015 | pmid = 26109185 | pmc = 4510619 | doi = 10.14814/phy2.12409 }} In addition, patients with Duchenne muscular dystrophy also have elevated plasma lipoprotein levels, implying a primary state of dyslipidemia in patients.{{cite journal | vauthors = White Z, Hakim CH, Theret M, Yang NN, Rossi F, Cox D, Francis GA, Straub V, Selby K, Panagiotopoulos C, Duan D, Bernatchez P | title = High prevalence of plasma lipid abnormalities in human and canine Duchenne and Becker muscular dystrophies depicts a new type of primary genetic dyslipidemia | journal = Journal of Clinical Lipidology | volume = 14 | issue = 4 | pages = 459–469.e0 | date = July 2020 | pmid = 32593511 | pmc = 7492428 | doi = 10.1016/j.jacl.2020.05.098 | s2cid = 219741257 }}

Duchenne muscular dystrophy is the most common type of muscular dystrophy; it affects about one in 5,000 males at birth. Duchenne muscular dystrophy has an incidence of one in 3,600 male infants.

In the US, a 2010 study showed a higher amount of those with Duchenne muscular dystrophy age ranging from 5 to 54 who are Hispanic compared to non-Hispanic Whites, and non-Hispanic Blacks.{{cite web |url=https://www.cdc.gov/ncbddd/musculardystrophy/features/key-findings-population-duchenne.html |title=Population-Based Prevalence of Duchenne and Becker Muscular Dystrophies in the United States |date=5 January 2018 |publisher=U.S. Centers for Disease Control and Prevention (CDC) |access-date=18 November 2018 |archive-date=18 November 2018 |archive-url=https://web.archive.org/web/20181118081731/https://www.cdc.gov/ncbddd/musculardystrophy/features/key-findings-population-duchenne.html |url-status=live }}{{cite journal | vauthors = Romitti PA, Zhu Y, Puzhankara S, James KA, Nabukera SK, Zamba GK, Ciafaloni E, Cunniff C, Druschel CM, Mathews KD, Matthews DJ, Meaney FJ, Andrews JG, Conway KM, Fox DJ, Street N, Adams MM, Bolen J | title = Prevalence of Duchenne and Becker muscular dystrophies in the United States | journal = Pediatrics | volume = 135 | issue = 3 | pages = 513–21 | date = March 2015 | pmid = 25687144 | pmc = 4477633 | doi = 10.1542/peds.2014-2044 }}

File:G. Duchenne-2.jpg

The disease was first described by the Neapolitan physician Giovanni Semmola in 1834 and Gaetano Conte in 1836.{{cite web |url=http://www.cardiomiologia.unina2.it/index.php?option=com_content&view=article&id=54&Itemid=58 |title=Cardiomiologia e Genetica Medica |trans-title=Cardiomyology and Medical Genetics |language=it | vauthors = Politano L |publisher=Seconda Università degli Studi di Napoli |access-date=24 August 2015 |url-status=live |archive-url=https://web.archive.org/web/20150704203015/http://www.cardiomiologia.unina2.it/index.php?option=com_content&view=article&id=54&Itemid=58 |archive-date=4 July 2015 }}{{cite web |url=http://www.uildm.org/archivio_dm/156/scienza/37conteweb.shtml |title=Da Conte a Duchenne |trans-title=By Conte in Duchenne |language=it | vauthors = De Rosa G |date=October 2005 |work=DM |publisher=Unione Italiana Lotta alla Distrofia Muscolare |access-date=24 August 2015 |archive-url=https://web.archive.org/web/20160304000807/http://www.uildm.org/archivio_dm/156/scienza/37conteweb.shtml |archive-date=4 March 2016 }}{{cite journal | vauthors = Nigro G | title = One-hundred-seventy-five years of Neapolitan contributions to the fight against the muscular diseases | journal = Acta Myologica | volume = 29 | issue = 3 | pages = 369–391 | date = December 2010 | pmid = 21574522 | pmc = 3146338 }} However, Duchenne muscular dystrophy is named after the French neurologist Guillaume-Benjamin-Amand Duchenne (1806–1875), who in the 1861 edition of his book Paraplégie hypertrophique de l'enfance de cause cérébrale, described and detailed the case of a boy who had this condition. A year later, he presented photos of his patient in his Album de photographies pathologiques. In 1868, he gave an account of 13 other affected children. Duchenne was the first to do a biopsy to obtain tissue from a living patient for microscopic examination.{{cite web |url=http://www.medterms.com/script/main/art.asp?articlekey=11686 |title=Duchenne muscular dystrophy |work=Medterms |publisher=Medterms.com |date=27 April 2011 |access-date=16 February 2013 |url-status=live |archive-url=https://web.archive.org/web/20120806222735/http://www.medterms.com/script/main/art.asp?articlekey=11686 |archive-date=6 August 2012 }}{{WhoNamedIt|doctor|950|Duchenne de Boulogne}}

As of 2023, the US states Ohio and New York require newborns to be screened for Duchenne muscular dystrophy.{{cite web |title=When time is muscle: One dad shares his story to advocate for Duchenne newborn screening |url=https://www.sarepta.com/newsroom/when-time-muscle-one-dad-shares-his-story-advocate-duchenne-newborn-screening |publisher=Sarepta Therapeutics}}{{cite web | title=Duchenne Added to New York State's Newborn Screening Panel | website=Parent Project Muscular Dystrophy | date=25 October 2023 | url=https://www.parentprojectmd.org/duchenne-added-to-new-york-states-newborn-screening-panel/ | access-date=15 January 2025}} As of 2024, Minnesota requires newborn screening.{{cite web | title=Duchenne muscular dystrophy (DMD) added to Minnesota's newborn screening panel | website=MN Dept. of Health | date=26 January 2024 | url=https://www.health.state.mn.us/news/pressrel/2024/newborn012624.html | access-date=15 January 2025}}

• Alfredo Ferrari was an Italian automotive engineer, the eldest son of automaker Enzo Ferrari, and the planned heir to his father's sports car company, Ferrari. Alfredo died of DMD on 30 June 1956 at the age of 24.{{cite web |url= https://abcnews.go.com/Business/ferrari-family/story?id=34626955 |title= What You Didn't Know About the Ferrari Family |author= Susanna Kim |date= 21 October 2015 |publisher= ABC News |access-date= 31 August 2023 |archive-date= 31 August 2023 |archive-url= https://web.archive.org/web/20230831063328/https://abcnews.go.com/Business/ferrari-family/story?id=34626955 |url-status= live }}{{cite web |url= https://gearshifters.org/ferrari/how-did-dino-ferrari-die/ |title= How Did Dino Ferrari Die? |author= The GearShifters Team |date= 13 September 2022 |publisher= GearShifters |access-date= 31 August 2023 |archive-date= 31 August 2023 |archive-url= https://web.archive.org/web/20230831063316/https://gearshifters.org/ferrari/how-did-dino-ferrari-die/ |url-status= live }}
• Rapper and disability rights advocate Darius Weems had the disease and used his notoriety to raise awareness and funds for treatment, as seen in the documentary Darius Goes West (2007).{{cite web |url=https://abcnews.go.com/Health/darius-weems-chapter-rap-star-duchenne-muscular-dystrophy/story?id=17779732 |first1=Cynthia|last1=McFadden|first2=Eric|last2=Johnson|first3=Lauren|last3=Effron|title=Darius Weems' Next Chapter: Rap Star With Duchenne Muscular Dystrophy Tries Clinical Trial |website=ABC News |date=22 November 2012 |access-date=29 June 2016 |url-status=live |archive-url=https://web.archive.org/web/20160805211715/https://abcnews.go.com/Health/darius-weems-chapter-rap-star-duchenne-muscular-dystrophy/story?id=17779732 |archive-date=5 August 2016 }} He died at the age of 27 in 2016.{{cite web |url= https://abcnews.go.com/Health/disability-rights-activist-darius-weems-loses-battle-duchenne/story?id=42708683 |title= Disability Rights Activist Darius Weems Loses Battle with Duchenne Muscular Dystrophy |author= Eric Johnson |date= 10 October 2016 |publisher= ABC News |access-date= 31 August 2023 |archive-date= 31 August 2023 |archive-url= https://web.archive.org/web/20230831065221/https://abcnews.go.com/Health/disability-rights-activist-darius-weems-loses-battle-duchenne/story?id=42708683 |url-status= live }}
• Jonathan Evison's novel, The Revised Fundamentals of Caregiving, published in 2012, depicted a young man affected by the disease. In 2016, Netflix released The Fundamentals of Caring, a film based on the novel.{{cite web |vauthors=Berkshire G |title=Sundance Film Review: 'The Fundamentals of Caring' |url=https://variety.com/2016/film/reviews/the-fundamentals-of-caring-film-review-sundance-1201686813/ |website=Variety |access-date=21 October 2021 |date=23 January 2016 |archive-date=21 October 2021 |archive-url=https://web.archive.org/web/20211021230638/https://variety.com/2016/film/reviews/the-fundamentals-of-caring-film-review-sundance-1201686813/ |url-status=live}}
• In 2024, Netflix released a documentary film about a young man with the disease, The Remarkable Life of Ibelin. The film explores the life of Mats Steen and the impact he had on his World of Warcraft guild Starlight, where Mats spent much of his time.{{Cite web |last=Grobar |first=Matt |date=19 January 2024 |title=Netflix Snaps Up Sundance Doc 'Ibelin' From 'The Painter And The Thief' Helmer Benjamin Ree |url=https://deadline.com/2024/01/ibelin-documentary-acquired-netflix-sundance-1235797191/ |access-date=28 January 2024 |website=Deadline |language=en-US}}

{{update section|date=August 2019}}

Efforts are ongoing to find medications that either return the ability to make dystrophin or utrophin.{{cite journal | vauthors = Guiraud S, Davies KE | title = Pharmacological advances for treatment in Duchenne muscular dystrophy | journal = Current Opinion in Pharmacology | volume = 34 | pages = 36–48 | date = June 2017 | pmid = 28486179 | doi = 10.1016/j.coph.2017.04.002 | doi-access = free | title-link = doi }} Other efforts include trying to block the entry of calcium ions into muscle cells.{{cite journal | vauthors = Allen DG, Gervasio OL, Yeung EW, Whitehead NP | title = Calcium and the damage pathways in muscular dystrophy | journal = Canadian Journal of Physiology and Pharmacology |volume=88 |issue=2 |pages=83–91 |date=February 2010 |pmid=20237582 |doi=10.1139/Y09-058}}

Antisense oligonucleotides (oligos), structural analogs of DNA, are the basis of a potential treatment for 10% of people with Duchenne muscular dystrophy.{{cite journal | vauthors = Scoto M, Finkel R, Mercuri E, Muntoni F | title = Genetic therapies for inherited neuromuscular disorders | journal = The Lancet. Child & Adolescent Health | volume = 2 | issue = 8 | pages = 600–609 | date = August 2018 | pmid = 30119719 | doi = 10.1016/S2352-4642(18)30140-8 | s2cid = 52032568 | url = https://discovery.ucl.ac.uk/id/eprint/10055445/ | access-date = 16 November 2022 | archive-date = 17 August 2021 | archive-url = https://web.archive.org/web/20210817173451/https://discovery.ucl.ac.uk/id/eprint/10055445/ | url-status = live }} The compounds allow faulty parts of the dystrophin gene to be skipped when it is transcribed to RNA for protein production, permitting a still-truncated but more functional version of the protein to be produced.{{cite journal | vauthors = Dunckley MG, Manoharan M, Villiet P, Eperon IC, Dickson G | title = Modification of splicing in the dystrophin gene in cultured Mdx muscle cells by antisense oligoribonucleotides | journal = Human Molecular Genetics | volume = 7 | issue = 7 | pages = 1083–1090 | date = July 1998 | pmid = 9618164 | doi = 10.1093/hmg/7.7.1083 | doi-access = free | title-link = doi }} It is also known as nonsense suppression therapy.{{cite journal | vauthors = Finkel RS | title = Read-through strategies for suppression of nonsense mutations in Duchenne/ Becker muscular dystrophy: aminoglycosides and ataluren (PTC124) | journal = Journal of Child Neurology | volume = 25 | issue = 9 | pages = 1158–1164 | date = September 2010 | pmid = 20519671 | pmc = 3674569 | doi = 10.1177/0883073810371129 }}

Two kinds of antisense oligos, 2'-O-methyl phosphorothioate oligos (like Drisapersen) and Morpholino oligos (like eteplirsen), have tentative evidence of benefit and are being studied.{{cite press release | title=FDA grants accelerated approval to first drug for Duchenne muscular dystrophy | url=https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-first-drug-duchenne-muscular-dystrophy | publisher=U.S. Food and Drug Administration (FDA) | date=19 September 2016 | access-date=12 December 2016 | url-status=live | archive-url=https://web.archive.org/web/20161211184800/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm521263.htm | archive-date=11 December 2016 }} {{PD-notice}} Eteplirsen is targeted to skip exon 51. "As an example, skipping exon 51 restores the reading frame of ~ 15% of all the boys with deletions. It has been suggested that by having 10 AONs to skip 10 different exons it would be possible to deal with more than 70% of all DMD boys with deletions." This represents about 1.5% of cases.

File:Reading Frame.png

People with Becker's muscular dystrophy, which is milder than DMD, have a form of dystrophin that is functional even though it is shorter than normal dystrophin.{{cite journal | vauthors = England SB, Nicholson LV, Johnson MA, Forrest SM, Love DR, Zubrzycka-Gaarn EE, Bulman DE, Harris JB, Davies KE | title = Very mild muscular dystrophy associated with the deletion of 46% of dystrophin | journal = Nature | volume = 343 | issue = 6254 | pages = 180–182 | date = January 1990 | pmid = 2404210 | doi = 10.1038/343180a0 | s2cid = 4349360 | bibcode = 1990Natur.343..180E }} In 1990 England et al. noticed that a patient with mild Becker muscular dystrophy was lacking 46% of his coding region for dystrophin. This functional, yet truncated, form of dystrophin gave rise to the notion that shorter dystrophin can still be therapeutically beneficial. Concurrently, Kole et al. had modified splicing by targeting pre-mRNA with antisense oligonucleotides (AONs).{{cite journal | vauthors = Dominski Z, Kole R | title = Restoration of correct splicing in thalassemic pre-mRNA by antisense oligonucleotides | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 18 | pages = 8673–8677 | date = September 1993 | pmid = 8378346 | pmc = 47420 | doi = 10.1073/pnas.90.18.8673 | doi-access = free | title-link = doi | bibcode = 1993PNAS...90.8673D }} Kole demonstrated success using splice-targeted AONs to correct missplicing in cells removed from beta-thalassemia patients{{cite journal | vauthors = Lacerra G, Sierakowska H, Carestia C, Fucharoen S, Summerton J, Weller D, Kole R | title = Restoration of hemoglobin A synthesis in erythroid cells from peripheral blood of thalassemic patients | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 17 | pages = 9591–9596 | date = August 2000 |pmid=10944225 | pmc = 16909 | doi = 10.1073/pnas.97.17.9591 | doi-access = free | title-link = doi | bibcode = 2000PNAS...97.9591L }}{{cite journal | vauthors = Suwanmanee T, Sierakowska H, Lacerra G, Svasti S, Kirby S, Walsh CE, Fucharoen S, Kole R | title = Restoration of human beta-globin gene expression in murine and human IVS2-654 thalassemic erythroid cells by free uptake of antisense oligonucleotides | journal = Molecular Pharmacology | volume = 62 | issue = 3 | pages = 545–553 | date = September 2002 | pmid = 12181431 | doi = 10.1124/mol.62.3.545 }} Wilton's group tested exon skipping for muscular dystrophy.{{cite journal | vauthors = Wilton SD, Lloyd F, Carville K, Fletcher S, Honeyman K, Agrawal S, Kole R | title = Specific removal of the nonsense mutation from the mdx dystrophin mRNA using antisense oligonucleotides | journal = Neuromuscular Disorders | volume = 9 | issue = 5 | pages = 330–338 | date = July 1999 | pmid = 10407856 | doi = 10.1016/S0960-8966(99)00010-3 | s2cid = 20678312 }}{{cite journal | vauthors = Wilton SD, Fall AM, Harding PL, McClorey G, Coleman C, Fletcher S | title = Antisense oligonucleotide-induced exon skipping across the human dystrophin gene transcript | journal = Molecular Therapy | volume = 15 | issue = 7 | pages = 1288–1296 | date = July 2007 | pmid = 17285139 | doi = 10.1038/sj.mt.6300095 | doi-access = free | title-link = doi }}

Researchers are working on a gene editing method to correct a mutation that leads to Duchenne muscular dystrophy (DMD).{{cite journal | vauthors = Long C, Li H, Tiburcy M, Rodriguez-Caycedo C, Kyrychenko V, Zhou H, Zhang Y, Min YL, Shelton JM, Mammen PP, Liaw NY, Zimmermann WH, Bassel-Duby R, Schneider JW, Olson EN | title = Correction of diverse muscular dystrophy mutations in human engineered heart muscle by single-site genome editing | journal = Science Advances | volume = 4 | issue = 1 | pages = eaap9004 | date = January 2018 | pmid = 29404407 | pmc = 5796795 | doi = 10.1126/sciadv.aap9004 | bibcode = 2018SciA....4.9004L }} Researchers used a technique called CRISPR/Cas9-mediated genome editing, which can precisely remove a mutation in the dystrophin gene in DNA, allowing the body's DNA repair mechanisms to replace it with a normal copy of the gene.{{cite journal| vauthors = Cohen J |date=30 August 2018|title=Gene editing of dogs offers hope for treating human muscular dystrophy |journal=Science |doi=10.1126/science.aav2676 |s2cid=92204241}}{{cite journal | vauthors = Patmanathan SN, Gnanasegaran N, Lim MN, Husaini R, Fakiruddin KS, Zakaria Z | title = CRISPR/Cas9 in Stem Cell Research: Current Application and Future Perspective | journal = Current Stem Cell Research & Therapy | volume = 13 | issue = 8 | pages = 632–644 | date = 2018 | pmid = 29895256 | doi = 10.2174/1574888X13666180613081443 | s2cid = 48357156 }}

Genome editing through the CRISPR/Cas9 system is not currently feasible in humans. However, it may be possible, through advancements in technology, to use this technique to develop therapies for DMD in the future.{{cite journal | vauthors = Long C, McAnally JR, Shelton JM, Mireault AA, Bassel-Duby R, Olson EN | title = Prevention of muscular dystrophy in mice by CRISPR/Cas9-mediated editing of germline DNA | journal = Science | volume = 345 | issue = 6201 | pages = 1184–1188 | date = September 2014 | pmid = 25123483 | pmc = 4398027 | doi = 10.1126/science.1254445 | bibcode = 2014Sci...345.1184L }}{{cite news| vauthors = Wade N |title=Gene Editing Offers Hope for Treating Duchenne Muscular Dystrophy, Studies Find|url=https://www.nytimes.com/2016/01/01/science/gene-therapy-muscular-dystrophy.html|access-date=1 January 2016|work=The New York Times|date=31 December 2015|url-status=live|archive-url=https://web.archive.org/web/20160102195733/http://www.nytimes.com/2016/01/01/science/gene-therapy-muscular-dystrophy.html?_r=0|archive-date=2 January 2016}} In 2007, researchers did the world's first clinical (viral-mediated) gene therapy trial for Duchenne MD.{{cite journal | vauthors = Rodino-Klapac LR, Chicoine LG, Kaspar BK, Mendell JR | title = Gene therapy for duchenne muscular dystrophy: expectations and challenges | journal = Archives of Neurology | volume = 64 | issue = 9 | pages = 1236–1241 | date = September 2007 | pmid = 17846262 | doi = 10.1001/archneur.64.9.1236 | doi-access = free | title-link = doi }}

Biostrophin is a delivery vector for gene therapy in the treatment of Duchenne muscular dystrophy and Becker muscular dystrophy.{{cite journal | vauthors = Khurdayan VK, Bozzo J, Prous JR | title = Chronicles in drug discovery | journal = Drug News & Perspectives | volume = 18 | issue = 8 | pages = 517–522 | date = October 2005 | pmid = 16391721 | doi = 10.1358/dnp.2005.18.8.953409 }}

Several medications designed to address the root cause are under development, including gene therapy and antisense drugs. Other medications used include corticosteroids to slow muscle degeneration. Physical therapy, orthopedic braces, and corrective surgery may help with some symptoms while assisted ventilation may be required in those with weakness of breathing muscles. Outcomes depend on the specific type of disorder.{{cite web|title=NINDS Muscular Dystrophy Information Page|url=http://www.ninds.nih.gov/disorders/md/md.htm|website=NINDS|access-date=12 September 2016|date=4 March 2016|archive-url=https://web.archive.org/web/20160730004520/http://www.ninds.nih.gov/disorders/md/md.htm|archive-date=30 July 2016}}

In February 2024, the results of a 48-week trial with Vamorolone in patients with Duchenne muscular dystrophy (The VISION-DMD study) were published. Patients showed improvements in motor outcomes seen with 6 mg/kg/d of Vamorolone at 24 weeks of treatment and were maintained for 48 weeks of treatment. As well, bone morbidities of prednisone (stunting of growth and declines in serum bone biomarkers) were reversed when treatment transitioned to Vamorolone.{{cite web |title=Catalyst Pharmaceuticals Announces Publication of Santhera Pharmaceutical's VISION-DMD Vamorolone (AGAMREE®) Study Results in the Peer-Reviewed Journal Neurology |url=https://finance.yahoo.com/news/catalyst-pharmaceuticals-announces-publication-santhera-140000469.html?guccounter=1&guce_referrer=aHR0cHM6Ly9kb2NzLmdvb2dsZS5jb20v&guce_referrer_sig=AQAAADNPPj0NPw-gub70B_oNcSW63l2QCXJb48mbNjL0VPkd7xaH3t2Wk4NKKtsdR7dqmVAoJmei4V_ZVelSnNgUuLdGSffwdEwqoQtoR-kxW337E-TkSNdqypggpDbSTwC65xE04gLQ5CYz4p_Ibw8bWilS3mv2GZdgv3yPPJBJR3XU |website=Yahoo Finance |publisher=Catalyst Pharmaceuticals, Inc.}}

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{{Medical resources

| DiseasesDB = 3985

| ICD10 = {{ICD10|G|71|0|g|70}}

| ICD9 = {{ICD9|359.1}}

| ICDO =

| OMIM = 310200

| MedlinePlus = 000705

| eMedicineSubj =

| eMedicineTopic =

| MeshID = D020388

| Orphanet = 98896

}}

{{Muscular Dystrophy}}

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Category:Rare diseases

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