Living with Duchenne Muscular Dystrophy: Treatment and Care Essentials 

This blog is designed to provide information about Duchenne Muscular Dystrophy for those living with this condition, their caregivers, loved ones, and anyone interested in learning about this disease. Here, you’ll find information about what Duchenne Muscular Dystrophy is, how it is diagnosed, the symptoms, and both current and investigational treatments.

What is Duchenne Muscular Dystrophy?

Duchenne Muscular Dystrophy (DMD) is a serious condition that affects the muscles, causing them to become weaker and deteriorate over time.¹ It belongs to a group of muscle disorders called dystrophinopathies, which also includes Becker Muscular dystrophy (BMD). ¹

In Europe and North America, Duchenne Muscular Dystrophy affects 6 out of every 100,000 individuals. ¹

What causes Duchenne Muscular Dystrophy?

Duchenne Muscular Dystrophy is a hereditary disease caused by different mutations (changes in the DNA) within the dystrophin gene. This gene is also mutated in Becker Muscular Dystrophy.  This gene is responsible for producing the dystrophin protein, which plays an important role in keeping muscle cells intact. It acts like a shock absorber in muscle cells, helping to protect muscle fibers from getting damaged during contractions. Without enough dystrophin, muscles gradually become damaged and weaker. ¹

The dystrophin gene is one of the largest in our body and is located on the X chromosome. Duchenne Muscular Dystrophy affects mainly males due to the way it is inherited. ^{1, 2} Males, who inherit one X chromosome from their mother and one Y chromosome from their father, will develop Duchenne Muscular Dystrophy if their X chromosome carries the mutation, as they lack a second X chromosome to compensate. Females have two X chromosomes, so if only one carries the mutation, the other usually provides enough dystrophin to prevent the disease. However, they can still pass the mutation on to their children (as “carriers”). ¹ Only around 10% of female carriers exhibit symptoms of the disease, and these are typically milder than those observed in males, with a few exceptions.²

Interested in understanding more about the type of mutations causing Duchenne Muscular Dystrophy? Check out this blog.

What are the symptoms?

Duchenne Muscular Dystrophy symptoms usually begin in early childhood, typically in boys between ages 2 and 3. ¹

Muscle weakness is the principal symptom of Duchenne Muscular Dystrophy. It usually begins in the legs and pelvis, later spreading to other parts of the body like the arms or neck. Children who are affected might have difficulty jumping, running, and walking. Other symptoms include enlargement of the calves, a waddling gait, and an inward curve of the spine. Additionally, they may experience fatigue and learning difficulties. ^1,3

As Duchenne Muscular Dystrophy progresses, walking becomes increasingly difficult, and most children are likely to need a wheelchair by age 12.^1,3 Over time, the respiratory muscles may weaken, leading to breathing difficulties. Although a child may not complain of shortness of breath, problems that indicate poor respiratory function include headaches, mental dullness, difficulty concentrating or staying awake, and nightmares. The lack of dystrophin can also weaken the muscle layer in the heart, leading to cardiomyopathy, a condition where the heart struggles to pump blood effectively.⁴

Diagnosis of Duchenne Muscular Dystrophy

In the diagnosis of any form of muscular dystrophy, a physician usually begins by evaluating the patient’s family history and performing a physical examination.  Family history can help determine the inheritance pattern of the disorder, while the physical examination may show signs such as enlarged muscles, exaggerated curve in the lower back, unusual walking patterns, and reduced muscle reflexes.⁵

Physicians often also request to check a person’s blood to test for creatine kinase (CK), an enzyme that leaks out of damaged muscle. A high CK level suggests that the muscles are being harmed. However, the test does not show exactly what type of disorder may be causing it. ⁵ Additionally, other tests such as an electrocardiogram, an echocardiogram or a cardiac MRI may be performed to assess the heart’s function, as some people with Duchenne Muscular Dystrophy develop heart muscle weakness (cardiomyopathy). ⁵

A DNA test is also performed to see whether there is a mutation in the dystrophin gene, and if so, what type of mutation it is, and exactly where it occurs. If needed, a muscle biopsy (removal of a small muscle sample) can distinguish between different types of muscular dystrophy. However, muscle biopsies are less common today since most diagnoses can be confirmed through genetic testing. ⁵

For more information on genetic testing for Duchenne Muscular Dystrophy, check out this blog.

Treatment of Duchenne Muscular Dystrophy

While there is no cure for this disease, Duchenne Muscular Dystrophy treatments are available to help manage symptoms and improve quality of life.^3,6

The treatment for Duchenne Muscular Dystrophy may include:

Steroid drugs. Steroid drugs, such as glucocorticoids, are often started when a child is diagnosed or when muscle strength begins to decline.³ These drugs can slow down the loss of muscle strength as they reduce the rate of muscle cell death. ^3,6

Physical exercise. Gentle exercise, such as swimming and water exercises, can help maintain muscle strength and keep the cardiovascular system healthy.^3,6,7 However, it is important to first discuss with a doctor what exercises to perform and how much is appropriate, as too much exercise can cause muscle damage. ⁷

Physical therapy and orthopedic care can also play an important role in preventing tightening of muscles and joints (contractures) that can limit movement. Treatments may include gentle stretching exercises, using long leg braces to help with walking or wearing a plastic ankle-foot brace while sleeping. Surgery to release contractures may be required for those who have advanced symptoms of the disease.⁶ In young men with Duchenne Muscular Dystrophy, the spine can gradually curve, which can interfere with sitting, sleeping, and even breathing. Physical therapy can help keep the back as straight as possible, and surgery may be necessary in some cases to correct severe curvature.⁷

Nutrition. No special diet is typically required for people with Duchenne Muscular Dystrophy. However, excessive weight gain can become a problem for people who use power wheelchairs, take certain medications, or are not very active. For these people, calorie intake may be restricted to keep a healthy weight. ⁷ Individuals with Duchenne Muscular Dystrophy may also develop dysphagia (difficulty with swallowing) and may be referred to a speech and language therapist. ⁷

Cardiac care. Regular heart check-ups are essential for people with Duchenne Muscular Dystrophy, starting from an early age and continuing throughout life. While boys are more commonly affected, female carriers also face a higher-than-average risk of developing heart issues. Therefore, medical experts often recommend that both boys and girls undergo regular monitoring. ⁷

Respiratory care. As Duchenne Muscular Dystrophy progresses, breathing muscles weaken. It’s important to keep the airways clear, using devices or manual techniques to assist with coughing. In later stages, assisted ventilation may be required to ensure enough air gets into the lungs. ⁷

Evaluation of cognitive and behavioral disorders. Children with Duchenne Muscular Dystrophy who are experiencing learning difficulties can be evaluated by a developmental or pediatric neuropsychologist. Duchenne Muscular Dystrophy can be associated with increased rates of autism spectrum disorders, attention deficit hyperactivity disorder, anxiety, and depression, which may also require adequate medical management. ⁷

Genetic Therapy for Duchenne Muscular Dystrophy

In recent years, there has been significant progress in genetic therapies for Duchenne Muscular Dystrophy, which aim to correct the underlying genetic cause of the disease. Each of the therapies are designed to target a specific type of mutation. Consequently, they only work for a small subset of patients who possess that mutation.³

Gene Therapy. In Duchenne Muscular Dystrophy, gene delivery involves inserting a healthy gene into muscle cells to replace a faulty one.⁸ Elevidys (delandistrogene moxeparvovec-rokl), is the first and only approved gene therapy for patients with Duchenne Muscular Dystrophy. It uses a harmless virus (Adeno-Associated Virus, AAV), to deliver a gene that creates micro-dystrophin, a shortened but functional version of the dystrophin protein. ^8,9 Early clinical trial data suggest that boys treated taking Elevidys tend to have an improved motor function than expected without treatment.⁹

• As of 30^th August 2024, Elevidys was approved in the U.S. by the Food and Drug Administration (FDA) for children aged 4 or 5 who can walk and have a confirmed dystrophin mutation. It’s also approved for those who cannot walk under an accelerated approval pathway, which requires additional clinical testing to confirm its benefits (this investigation is ongoing). Elevidys is not yet approved outside the U.S. ^{9, 10, 11}

Other gene therapies are currently under investigation.

Exon skipping. Exons are parts of our DNA that carry the instructions for making different sections of a protein, similar to the pieces of a ‘puzzle’. When these exons come together, they create a complete and functional protein, with each exon adding a piece to the ‘puzzle.’ In Duchenne Muscular Dystrophy, some of these pieces are missing. Without these missing parts, the other pieces cannot fit well together, leading to the formation of a faulty dystrophin protein that does not work correctly. The general concept behind exon-skipping therapy for Duchenne is to remove some new pieces to help the remaining ones fit better together. This results in the formation of a shortened version of the dystrophin protein that can still work, though not perfectly.  Exon skipping creates a scenario similar to Becker Muscular Dystrophy, where, despite the absence of some exons, the remaining exons can still align and produce a shorter but partially functional protein.¹²

• As for 30^th August 2024, four exon-skipping therapies are approved by the FDA for Duchenne in the U.S.: Amondys 45 (casimersen), Exondys 51(eteplirsen), Viltepso (viltolarsen) and Vyondys 53 (golodirsen). These therapies treat Duchenne Muscular Dystrophy caused by specific mutations. ¹² Importantly, these therapies were approved under the accelerated pathway, with several clinical trials ongoing to collect more data on their potential benefits. Among these drugs, Viltepso is also approved in Japan.¹³

There are, additionally, other investigational therapies that are being researched in the laboratory:

Nonsense mutation readthrough. In some cases, Duchenne Muscular Dystrophy is caused by a nonsense mutation, which creates a “stop signal” in the gene, prematurely ending the production of dystrophin, resulting in a non-functional protein.^17,18 Nonsense mutation readthrough therapy involves using a small molecule that allows the cell to ignore this stop signal, allowing it to produce a full-length dystrophin protein. This approach is currently being investigated and is not available for people in the US. ¹⁹

Gene editing. Gene editing involves recognizing a specific DNA sequence and modifying it. Although there are different methods of gene editing, the CRISPR-Cas system has been increasingly studied in recent years. The CRISPR-Cas system uses a “template” to find a specific piece of DNA in a cell and then removes, replaces or inserts a piece of DNA at this location.^14,15 This technique is currently being investigated in the laboratory and is not available for human use.¹⁶

Interested in knowing more about CRISPR-Cas and its challenges in Duchenne Muscular Dystrophy? Read this blog.

Conclusions

Duchenne Muscular Dystrophy (DMD) is a serious condition that affects the muscles, causing them to become weaker and deteriorate over time. While there is no cure, various treatments can help manage symptoms and improve the quality of life. These Duchenne Muscular Dystrophy treatment plans may include physical exercise, orthopedic interventions, assistive devices, heart monitoring, or respiratory care. In recent years, significant progress has been made in genetic therapies for Duchenne Muscular Dystrophy. Elevidys is the first approved gene therapy in the U.S. for Duchenne Muscular Dystrophy. Exon skipping therapies, such as Amondys 45, Exondys 51, Viltepso, and Vyondys 53 are also approved in the U.S.. These therapies were given accelerated approval by the FDA, and further studies are ongoing to confirm their benefits. Other treatments are in clinical trial phase, and other therapies, like gene editing, are still in the research phase and aren’t available for people.

Are you affected by Duchenne Muscular Dystrophy and want to explore your treatment options?

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You can book a call with a Patient Navigator to discuss your options and learn more about participating in clinical trials .