Özge’s background is in research; she holds a MSc. in Molecular Genetics from the University of Leicester and a PhD. in Developmental Biology from the University of London. Özge worked as a bench scientist for six years in the field of neuroscience before embarking on a career in science communication. She worked as the research communication officer at MDUK, a UK-based charity that supports people living with muscle-wasting conditions, and then a research columnist and the managing editor of resource pages at BioNews Services before joining Rare Disease Advisor.
The first person to report on muscular dystrophy was Sir Charles Bell, a Scottish surgeon, anatomist, physiologist, and neurologist, who wrote an essay in 1830 about a disease that led to progressive muscle weakness in boys.1
Six years later, 2 Italian physicians, Giovanni Semmola and Gaetano Conte, wrote about 2 brothers who had symptoms of generalized weakness. The brothers showed signs of muscle damage, which was replaced with fat and connective tissue.
Later, more cases of patients affected by progressive muscle weakness who lost the ability to walk and who died at a young age appeared in the medical literature.
In 1836, Conte and Gioja described the case of 2 brothers with progressive muscle weakness, and in 1852, Edward Meryon described a family with 4 boys with significant muscle changes.
In 1868, French neurologist Guillaume Benjamin Amand Duchenne became the first scientist to give a comprehensive account of 13 boys affected by severe disease, which would later be referred to as Duchenne muscular dystrophy (DMD).1
The milder form of DMD was first described by the German doctor Peter Emil Becker in the 1950s, who gave the disease his own name.2
First Muscular Dystrophy Gene to Be Cloned
The first gene to be identified by positional cloning was the DMD gene.3 The entire gene was cloned by Dr. Michael Koenig in 1987. Since DMD was inherited in an X-linked pattern, it was known that the gene was located on the X chromosome. It was later found that the gene resides on chromosome Xp21. The DMD gene was finally identified as the largest human gene known to date. It measures more than 2.2 Mb and has a transcript made up of 79 exons measuring 14skb.4 Mutations in this gene are also known to cause Becker muscular dystrophy (BMD).
Today, there are more than 30 distinct genetic diseases that are known to cause progressive muscle weakness and degeneration.5 The 9 main types are DMD, BMD, congenital muscular dystrophy, distal muscular dystrophy, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy (FSHD), limb-girdle muscular dystrophy (LGMD), and oculopharyngeal muscular dystrophy (OPMD).
History of DMD Treatment
Since the earliest descriptions of DMD, several approaches have been used to treat the disease. Some of these were used empirically, while others were based on reports of the biochemical or metabolic abnormalities seen in humans and animal models.6
Duchenne was treating his patients with electrical stimulations; however, it is not known how they were responding to this type of treatment. A 1992 study described the case of 7 patients affected by DMD and 2 affected by BMD who were treated with low-frequency electrical stimulation of the right tibialis anterior muscle. After 9 months of treatment, 5 boys showed improvements in torques in the treated muscles compared to in the non-treated muscles.7 However, in 1997, it was shown that electrical stimulation could actually lead to premature degeneration of the muscle fibers by activating proteases.8
Researchers also attempted other approaches to treat DMD or delay the progression of the disease. These included cholinesterase inhibitors, antioxidant drugs acting on biochemical and metabolic pathways, drugs acting on growth and muscle function, those producing changes in sarcolemma and calcium accumulation, drugs affecting blood flow to the muscles, antifibrotics to reduce the proliferation of conjunctive tissue, and anti-inflammatory drugs.6
None of these drugs could substantially change the course of the disease and most of them produced controversial results.
Corticosteroids were the only drugs that were shown to prolong muscle function and strength, maintain walking ability, and improve daily functions, quality of life, and survival. Prednisone was first used in 1974 to treat DMD and is still routinely prescribed today.9
With a better understanding of the genetic cause of the disease, drugs attempting to increase the production of dystrophin protein have been developed and tested in clinical trials. Some of these did produce some promising results, and there are currently 4 exon-skipping drugs approved by the US Food and Drug Administration (FDA) that have been shown to increase the production of dystrophin in muscle cells. However, the current data available is not able to show that these treatments are effective in DMD.10
There are several treatment approaches still in clinical trials exploring different avenues to treat DMD, including antioxidants to prevent muscle fiber injury, antifibrotics, anti-myostatins to increase muscle mass, and anti-inflammatory drugs.6 There are also cell and gene therapy approaches that could treat or even cure DMD and other types of muscular dystrophy in the future.
- Huml RA. Muscular dystrophy: historical background and types. In: Huml RA, ed. Muscular Dystrophy. Springer; 2015:5-7.
- Ho R, Nguyen ML, Mather P. Cardiomyopathy in Becker muscular dystrophy: overview. World J Cardiol. 2016;8(6):356-361. doi:10.4330/wjc.v8.i6.356
- Hoffman EP. Muscular dystrophy: identification and use of genes for diagnostics and therapeutics. Arch Pathol Lab Med. 1999;123(11):1050-1052. doi:10.5858/1999-123-1050-MD
- Gao QQ, McNally EM. The dystrophin complex: structure, function, and implications for therapy. Compr Physiol. 2015;5(3):1223–1239. doi:10.1002/cphy.c140048
- Muscular dystrophy: hope through research. National Institute of Neurological Disorders and Stroke. Accessed June 23, 2021.
- Werneck LC, Lorenzoni PJ, Ducci RDP, Fustes OH, Kay CSK, Scola RH. Duchenne muscular dystrophy: an historical treatment review. Arq Neuropsiquiatr. 2019;77(8):579-589. doi:10.1590/0004-282X20190088
- Zupan A. Long-term electrical stimulation of muscles in children with Duchenne and Becker muscular dystrophy. Muscle Nerve. 1992;15(3):362-367. doi:10.1002/mus.880150316
- Yoshida M, Matsuzaki T, Date M, Wada K. Skeletal muscle fiber degeneration in mdx mice induced by electrical stimulation. Muscle Nerve. 1997;20(11):1422-1432. doi:10.1002/(sici)1097-4598(199711)20:11<1422::aid-mus10>3.0.co;2-3
- Drachman DB, Toyka KV, Myer E. Prednisone in Duchenne muscular dystrophy. The Lancet. 1974;2(7894):1409-1412. doi:10.1016/s0140-6736(74)90071-3
- Shimizu-Motohashi Y, Murakami T, Kimura E, Komaki H, Watanabe N. Exon skipping for Duchenne muscular dystrophy: a systematic review and meta-analysis. Orphanet J Rare Dis. 2018;13(1):93. doi:10.1186/s13023-018-0834-2
Article reviewed by Debjyoti Talukdar, MD, on July 1, 2021.