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✍🏻 Georgia Gray | MSc Genomic Medicine student at the University of Manchester
If you or someone who know has been affected by muscular dystrophy please please visit the Muscular Dystrophy UK or PPMD websites for support.
What is muscular dystrophy? 🦵🏿
The term muscular dystrophy (MD) is used to describe multiple distinct conditions which are linked by their shared main features: progressive muscle weakness and muscle loss.
Duchenne Muscular Dystrophy (DMD)
Becker Muscular Dystrophy (BMD)
Congenital Muscular Dystrophy
Myotonic Dystrophy
Facioscapulohumeral Muscular Dystrophy
Limb-girdle Muscular Dystrophy
These types of MD are distinguished based on factors such as their age of onset, the severity of symptoms, and the affected muscle groups. For instance, Facioscapulohumeral MD primarily affects the muscles in the face, shoulders, and upper arms, whereas limb-girdle MD affects the muscles in the hips and thighs.
While the specific symptoms seen in MD vary by type, the general outcome of muscle loss is pain and mobility issues. Furthermore, other body systems can be affected – sometimes, cardiovascular problems and learning difficulties can be seen in individuals with MD.
DMD is usually diagnosed in boys by the age of 5. Typically, muscle weakness progresses to a point where patients are reliant on wheelchairs by their teens. Contrastingly, BMD usually manifests later in life with milder symptoms.
The life expectancy of individuals with MD can be significantly reduced. For example, the majority of individuals with DMD pass away in their 30s due to complications related to heart or respiratory failure. Conversely, many people with BMD have a normal lifespan.
How common is MD? 🔢
Overall, MD impacts roughly 70,000 people in the UK.
DMD is the most common form of MD and affects around 1 in every 3,500 male newborns. In the UK, this translates to around 100 male infants born with the condition each year. Due to the way in which DMD is inherited, this condition is only seen in males.
What causes MD? 🧬
MD is a genetic condition; it is caused by changes, or mutations, in a person’s genes.
These changes are present from birth, although symptoms of the condition might not show until later in life.
Specifically, MD is caused by mutations in a gene responsible for producing a protein called dystrophin. Dystrophin holds a critical role within our muscles, providing stability and protecting them from damage during contraction. Moreover, dystrophin contributes to how our cells communicate with each other.
Various types of mutations can occur in the dystrophin gene, which is the largest human gene. Most commonly, DMD and BMD are caused by mutations which delete certain sections of the gene.
Depending on which portions of the gene are missing, this can result in either the complete absence of dystrophin or the production of a smaller, partially functional version of it.
Without properly functioning dystrophin, muscles are more susceptible to damage during their contraction and relaxation cycles. This is what causes the symptoms of MD.
People with DMD typically have gene mutations that cause dystrophin to be entirely absent.
In contrast, those with BMD tend to have gene mutations that give rise to a smaller version of dystrophin. This is why the two conditions vary in terms of their severity.
Why is MD mostly seen in males rather than females? 👦🏽
The reason why these conditions affect males and females differently lies in the location of the dystrophin gene on the X chromosome. This leads to a phenomenon known as ‘X-linked inheritance’.
Females have two X chromosomes, whereas males have an X chromosome and a Y chromosome. As a result, males only have one copy of the genes that are on the X chromosome, but females have two copies.
Put simply, if a female has one mutated copy of the dystrophin gene, but retains a normal ‘backup’ copy, dystrophin can still be made using that backup copy. Conversely, when a male carries a mutated copy of the dystrophin gene, it leads to the production of either partially functional or no dystrophin whatsoever. There is no backup dystrophin copy to produce normal dystrophin and compensate for this, which leads to MD.
Consequently, females can carry a mutated copy of dystrophin and not show any symptoms of MD. Nonetheless, in some cases, these carrier females can experience mild MD symptoms such as muscle weakness, cramps, pain, and in some cases heart problems.
Almost a third of all DMD cases occur in individuals with no family history of the condition. These instances are termed ‘de novo’ cases and occur spontaneously, probably in pregnancy. The remainder are cases where the condition has been inherited.
How is MD diagnosed? 🩺
In the case of DMD, symptoms tend to emerge at a young age.
Children with DMD often display telltale signs like a waddling gait (a distinctive way of walking) or Gowers sign (an unusual method of getting up from a seated or lying position). Frequently, developmental delays are observed in areas such as walking, overall motor skills, and speech among children with DMD.
Upon medical evaluation and investigation of the patient’s family history, blood tests are commonly conducted. These tests measure the level of an enzyme called creatine kinase in the blood, which indicates whether muscle breakdown is occurring.
Furthermore, a genetic test is performed to identify mutations in the DMD gene. To assess the quantity of dystrophin in the patient’s muscle, a muscle biopsy might be conducted. This involves extracting a small muscle sample from the patient, which is then examined under a microscope.
How is MD treated? 💊
Unfortunately, there is no cure for MD. Current treatments focus on managing symptoms of the condition.
- Exercise and physiotherapy to address mobility issues and breathing difficulties.
- Steroids and creatine supplements to enhance muscle strength.
- ACE inhibitors, beta blockers, or pacemakers to manage heart problems.
Researchers are actively investigating novel treatments for MD. One such development is Ataluren, a new medicine designed to encourage cells to ignore errors in the dystrophin gene and produce more dystrophin. However, this treatment is only suitable for patients with a specific type of dystrophin gene mutation and who are still able to walk.
In June, a significant milestone was reached with the announcement of the first FDA-approved gene therapy for Duchenne Muscular Dystrophy (DMD). This is a groundbreaking development in the area of DMD therapies, which predominantly consist of symptomatic treatments.
Named ‘Elevidys’, this pioneering treatment is suitable for paediatric patients aged 4 to 5 who harbour a confirmed dystrophin gene mutation. An altered version of the dystrophin gene is delivered to the patient via a single intravenous injection. This altered dystrophin gene produces shortened but functional dystrophin.
Unlike other available treatment options that exhibit effectiveness only in individuals with specific gene alterations, Elevidys distinguishes itself by its ability to treat a wide spectrum of patients. This aspect of the treatment provides a pivotal advantage, underlining the significance of Elevidys’ FDA approval.
Written by: Georgia Gray (Content Writer)
Edited by: Grace Pountney (Founder and Director)
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