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.
Muscular dystrophy is the name given to a group of diseases that leads to progressive muscle weakness and atrophy.1 There are many types of muscular dystrophy, all with different genetic causes. These include congenital muscular dystrophy, Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), facioscapulohumeral muscular dystrophy (FSHD), limb-girdle muscular dystrophy, Emery-Dreifuss muscular dystrophy, and oculopharyngeal muscular dystrophy (OPMD).
Duchenne muscular dystrophy is the most studied form of muscular dystrophy and even though there is currently no cure for the disease, there are several treatment options that can alleviate disease symptoms. There are also some treatments that address the underlying cause of the disease, such as exon skipping medications. Finally, a number of experimental treatments are in production that could help treat different aspects of DMD.
Corticosteroids can be used to treat DMD caused by any mutation in the DMD gene.2 They should be started before the plateau phase of the disease, generally around age 4 or 5. This is when the patient’s motor skills are no longer improving but have not yet deteriorated.
It is thought that corticosteroids work by reducing inflammation and maintaining muscle cell integrity. Research has shown that long-term corticosteroid treatment can delay the loss of muscle strength and function and reduce the risk of death.3 They can also be used to treat BMD.
However, corticosteroids have many side effects, especially with long-term use, including weight gain, delayed growth and puberty, osteoporosis, hypertension, cataracts, and behavioral changes.3
A sudden discontinuation of corticosteroids can cause an adrenal crisis. Therefore, therapy withdrawal should be done following the PJ Nicholoff steroid protocol.4
The 2 main corticosteroids prescribed in DMD and BMD are prednisone and deflazacort. Deflazacort is derived from prednisolone, and research has shown that deflazacort-treated patients experience significantly lower functional decline compared to those treated with prednisone.5
Deflazacort is marketed under the brand names Emflaza™ in the US and Calcort® in Europe.6,7
Duchenne muscular dystrophy is caused by mutations that disrupt the reading frame of the DMD gene. As a result, cells cannot produce any functional dystrophin protein, which is essential for muscle cell health.
Exon skipping is a treatment approach whereby masking certain portions of the DMD gene using antisense oligonucleotides (AOs) or ‘molecular patches’ that restores the reading frame.8 This means that cells can start to make a shorter, functional version of the dystrophin protein.
The US Food and Drug Administration (FDA) has approved 4 exon-skipping drugs for the treatment of DMD. Two of these are to treat patients with a mutation amenable to exon 53 skipping – Vyondys 53™ (golodirsen) and Viltepso® (viltolarsen), one is for patients with a mutation amenable to exon 51 skipping – Exondys 51® (eteplirsen), and one is for the treatment of patients with a mutation amenable to exon 45 skipping – Amondys 45™ (casimersen).
It is estimated that 13% of patients with DMD have mutations amenable to exon 51 skipping, 8% have mutations amenable to exon 53 skipping, and 8% have mutations amenable to exon 45 skipping.9
Results of clinical trials have shown that treatment with these exon-skipping drugs increases the levels of dystrophin production. However, there is currently no available data showing evidence of clinical benefits of these treatments in DMD. This could be partly due to the relatively small number of randomized controlled trials and the relatively small number of participants in these trials.10
There are also a number of experimental treatments that are currently in clinical trials for the potential treatment of DMD and other types of muscular dystrophy.11
Gene therapy drugs aim to deliver a healthy copy of the mutated gene to the body using modified adeno-associated viruses (AAV). These include Pfizer’s PF-06939926, Sarepta’s SRP-9001, and Solid Biosciences’ SGT-001, which all aim to deliver a healthy but smaller version of the DMD gene to the body. PF-06939926 is in an early Phase 3 clinical trial, SRP-9001 is in a Phase 2 clinical trial, and SGT-001 is in a Phase 1 clinical trial for the treatment of DMD.
There are also anti-fibrotic drugs like Pamrevlumab to combat fibrosis, therapies aimed at reducing inflammation, and medications like Rimeporide aimed to regulate calcium flow, which is increased in muscular dystrophies such as DMD due to the instability of the muscle cell membrane.
There are also experimental treatments that aim to induce muscle development and therapies aimed at increasing or enhancing the activity of mitochondria in muscle cells to improve muscle function.
Finally, there are some treatment options like Ifetroban aimed at improving heart muscle function and cardiomyocyte protection.
- Overview – muscular dystrophy. NHS. Accessed June 23, 2021.
- Steroids (corticosteroids). Parent Project Muscular Dystrophy. Accessed June 23, 2021.
- Torgan C. Optimizing steroid treatment for Duchenne muscular dystrophy. National Institute of Arthritis and Musculoskeletal and Skin Diseases. March 8, 2018. Accessed June 23, 2021.
- Kinnett K, Noritz G. The PJ Nicholoff steroid protocol for Duchenne and Becker muscular dystrophy and adrenal suppression. PLoS Curr. 2017;9:ecurrents.md.d18deef7dac96ed135e0dc8739917b6e. doi:10.1371/currents.md.d18deef7dac96ed135e0dc8739917b6e
- McDonald CM, Sajeev G, Yao Z, et al.; ACT DMD Study Group and the Tadalafil DMD Study Group. Deflazacort vs prednisone treatment for Duchenne muscular dystrophy: a meta-analysis of disease progression rates in recent multicenter clinical trials. Muscle Nerve. 2020;61(1):26-35. doi:10.1002/mus.26736
- Access Data FDA, Emflaza. February 2017.
- Calcort. EMC. January 2, 2021. Accessed June 28, 2021.
- What is exon skipping and how does it work? Muscular Dystrophy UK. Accessed June 23, 2021.
- Mutation-specific therapies. Parent Project Muscular Dystrophy. Accessed June 23, 2021.
- 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
- Duchenne drug development pipeline. Parent Project Muscular Dystrophy. Accessed June 23, 2021.
Article reviewed by Debjyoti Talukdar, MD on July 1, 2021.