Rare Disease Day takes place each year on the last day of February, with the aim of increasing awareness of rare diseases and the impact they have on the lives of patients and their families .
More than 6,000 rare diseases have been identified to date, collectively affecting over 300 million people globally . However, there is no known cure for the majority of rare diseases and the diagnosis and treatment of patients is often impeded by a lack of knowledge and data . In the lead up to Rare Disease Day, this article takes a closer look at one such rare disease, Duchenne muscular dystrophy (DMD).
What is DMD?
DMD is a severe form of muscular dystrophy characterised by progressive muscle wasting and weakness. It is caused by a mutation in the gene encoding the protein dystrophin and primarily affects boys, with an estimated incidence of 1 in 3,500 male births [2, 3].
Approximately 2,500 people in the UK and 300,000 people around the world are living with DMD .
Signs and symptoms of DMD typically manifest between the ages of 3 and 5 years, with infants exhibiting ambulatory deficiencies such as difficulty standing and climbing stairs. Wasting starts in the muscles of the upper arms and legs and the pelvic region, followed by the forearms and lower legs [2, 3]. Muscle deterioration continues throughout childhood, further impairing physical function and resulting in most children with DMD requiring a wheelchair by adolescence [2, 3]. As the disease progresses, patients exhibit curvature of the spine and contractures as joints become fixed [2, 3]. Cardiomyopathy and respiratory issues develop during the teenage years, and many patients require the use of a ventilator. The average life expectancy of someone with DMD is the mid-twenties, with cardiac or respiratory failure being common causes of death [2, 3, 5].
What causes DMD?
Patients with DMD have a mutation in the gene that codes for an important protein called dystrophin. This gene is located on the X chromosome and is inherited in a recessive pattern, although de novo mutations are possible [2, 3]. Conditions caused by mutations on the X chromosome are called X-linked disorders and mainly affect boys [2, 3]. Females rarely experience DMD but can be ‘carriers’ of the mutation .
The dystrophin protein is expressed in skeletal and cardiac muscle, where it is important for maintaining the structural integrity of muscle fibres . Dystrophin forms a complex with other proteins, which is important for anchoring muscle fibres to their environment and transmitting signals . The absence of dystrophin in DMD impairs the stability of muscle fibres and leads to a continual cycle of damage and regeneration, culminating in fibre necrosis, fibrosis and fat accumulation [2, 3, 5].
Figure 1. The function of the dystrophin protein. Dystrophin links with proteins at the cell membrane of muscle fibres (the sarcolemma) to connect the cytoskeleton to the surrounding environment. Dystrophin, and the associated protein complex, can be thought of as a scaffold that stabilises muscle fibres and is important for relaying signals. A lack of dystrophin, as seen in DMD, results in damage to the fibre, leading to muscle wasting and weakness.
Treatment and research
Currently, there is no cure for DMD, and treatment instead focuses on symptom management and physical therapy; however, this does not directly target the cause of DMD (the absence of the dystrophin protein). Gene replacement therapy seeks to address this by using viruses to insert a functional gene into cells to replace the mutated version, allowing the cells to produce the relevant protein . The gene coding for dystrophin is one of the largest in the human genome, which makes it difficult to deliver it to cells. To overcome this, researchers are developing a smaller version of the dystrophin gene (‘micro-dystrophin’), which can fit inside viruses and provide sufficient information for cells to produce the protein .
Despite the encouraging progress being made, the treatment options for patients with DMD remain limited, highlighting the need for more research into this condition and other rare diseases. Raising awareness among the general public and policymakers is an integral part of this process and is a core aim of Rare Disease Day.
You can find out more information about Rare Disease Day and how you can get involved here: https://www.rarediseaseday.org/.
1. RareDiseaseDay.org. Rare Disease Day. Available at: https://www.rarediseaseday.org/. Accessed February 2021.
2. Venugopal V and Pavlakis S. Duchenne muscular dystrophy. In: StatPearls [Internet]. StatPearls Publishing; 2020. Available at: https://pubmed.ncbi.nlm.nih.gov/29493971/. Accessed February 2021.
3. National Organization for Rare Disorders. Duchenne muscular dystrophy. Available at: https://rarediseases.org/rare-diseases/duchenne-muscular-dystrophy/. Accessed February 2021.
4. Duchenne UK. What is Duchenne? Available at: https://www.duchenneuk.org/Pages/FAQs/Category/what-is-duchenne. Accessed February 2021.
5. Duchenne Research Fund. Duchenne muscular dystrophy. Available at: https://www.duchenne.org.uk/duchenne-facts/. Accessed February 2021.
6. Nowak KJ and Davies KE. Duchenne muscular dystrophy and dystrophin: Pathogenesis and opportunities for treatment. EMBO Rep 2004; 5 (9): 872–876.
7. Muscular Dystrophy Association. Duchenne muscular dystrophy (DMD). Available at: https://www.mda.org/disease/duchenne-muscular-dystrophy/research. Accessed February 2021.
Author: Tom O’Sullivan, Associate Medical Writer, Porterhouse Medical