Duchenne Muscular Dystrophy: diagnosis, clinical development and global research

Duchenne Muscular Dystrophy: diagnosis, clinical development and global research

Muscular dystrophy refers to a group of rare, genetic, progressive diseases that primarily affect the body’s muscles, causing them to weaken and deteriorate over time. While muscular dystrophies are often diagnosed in childhood, some types appear in adulthood. As the diseases progress, patients can experience muscle wastage and loss, which can severely affect their movement ability and sometimes their ability to breathe. There are around thirty types of muscular dystrophy each with differing symptoms and severity. One of the most common forms of muscular dystrophy is Duchenne Muscular Dystrophy.

Globally, Duchenne is the most prevalent form of muscular dystrophy in children. It primarily affects boys, and it is estimated to occur in approximately 1 in every 3,500 to 5,000 live male births worldwide, resulting in about 20,000 new cases annually. 

Angela Sarmiento Betancourt MD, expert at myTomorrows, a global healthtech company, specialising in clinical trial discovery and access, has shared her insights into muscular dystrophy, including its impact, why early diagnosis is essential, and an overview of global research and treatments.

The full-body impact of Duchenne muscular dystrophy

Duchenne Muscular Dystrophy (DMD) is a serious condition that affects the muscles, causing them to become weaker and deteriorate over time. In Europe and North America, Duchenne Muscular Dystrophy affects 6 out of every 100,000 individuals.

Duchenne is a genetic condition caused by different mutations (changes in the DNA) within the dystrophin gene. 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 fibres from getting damaged during contractions. Without enough dystrophin, muscles gradually become damaged and weaker.

The dystrophin gene is one of the largest in our body and is located on the X chromosome. While Duchenne Muscular Dystrophy is typically inherited, about one-third of cases arise from new mutations that occur spontaneously (with no family history). Males, who inherit one X chromosome from their mother and one Y chromosome from their father, are more likely to develop this condition. They 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”).  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. 

Why early diagnosis is important 

Duchenne is a form of muscular dystrophy that can lead to severe mobility issues. The symptoms usually begin in early childhood, typically in boys between ages 2 and 3. As Duchenne progresses, walking becomes increasingly difficult, and most children are likely to need a wheelchair by age 12. 

The diagnosis of Duchenne typically involves clinical evaluation, blood tests and genetic tests. Early signs of Duchenne are delayed walking, frequent falls and difficulty climbing stairs. A blood test to measure creatine kinase (CK) an enzyme released when muscle cells break down, and that is extremely elevated in Duchenne. Genetic testing is performed to confirm whether there is a mutation in the dystrophin gene, what type of mutation it is, and where it occurs. If needed, a muscle biopsy (removal of a small muscle sample) can be performed, to show the absence of dystrophin in the muscles. However, muscle biopsies are less common today since most diagnoses can be confirmed through genetic testing. 4,  

An early diagnosis of Duchenne will allow timely access to both genetic counselling and standards of care. For those who later have exhausted the standard of care and have an unmet medical need, they may potentially consider to clinical trials.

Prenatal Diagnosis

Genetic testing can be used to diagnose Duchenne before birth if a specific dystrophin mutation is known to be in the family. If a woman is pregnant and known to be a carrier of a Duchenne mutation, she may be offered prenatal testing.  Chorionic villus sampling (CVS) is a method in which tissue is removed from the placenta, around 11 weeks or later, and used as testing material. 

Couples who are at known risk of having a child with Duchenne may consider pre-implantation genetic diagnosis (PGD). This requires the couple conceives using in vitro fertilization (IVF). The embryos are tested at an early stage, and if there are embryos unaffected by Duchenne, these are transferred into the uterus. IVF and PGD processes carry social, financial, and emotional burdens and it can be helpful to discuss with a genetic counsellor and healthcare professional prior to making a decision.

Global research and clinical developments

Recent global research and clinical developments have significantly advanced the understanding and treatment of muscular dystrophy, in its many forms which is helping to improve patient care and treatment options. Furthermore, in December 2024, the Muscular Dystrophy Association (MDA) made a major research investment which awarded $5 million across 21 new research projects. All the projects are aimed at advancing treatments for neuromuscular diseases.

One of the many treatments currently being assessed in clinical development is the gene therapy technology CRISPR.

CRISPR technology 

People with DMD have a mutation in the dystrophin gene which renders them unable to make functional dystrophin protein, a critical protein for muscle function. Dystrophin gene mutations are like errors in the instructions for making dystrophin protein. Correcting those errors at the DNA level may be possible using gene editing technology called CRISPR-Cas9, which is currently undergoing preclinical research.

CRISPR aims to permanently correct dystrophin gene mutations in people with DMD, however CRISPR therapies for Duchenne are not yet widely available to patients and clinical research is still ongoing. 

Whilst CRISPR technology research indicates it may be used to treat DMD, there are still obstacles to overcome. CRISPR can only gain access and correct a proportion of muscle cells. It is not currently known exactly what percentage of muscle cells need to be corrected to have a therapeutic benefit for humans. However, research suggests that for people with DMD the technology could deliver a 15% improvement in dystrophin levels.

Maintaining long-term positive results is also a likely challenge because of the natural turnover of skeletal muscle cells. Replacement muscle cells grow from precursor cells called “satellite cells” that are typically not edited by CRISPR-Cas9. Over time the edited muscle cells may become diluted by non-edited muscle cells. Since people develop antibodies against AAV and CRISPR-Cas9, a second dose of the same treatment would not be effective.

 

Muscular Dystrophy is a group of rare, genetic, progressive diseases that primarily affect the body’s muscles, causing them to weaken and deteriorate over time. The most common form of muscular dystrophy is Duchenne Muscular Dystrophy (DMD), a genetic disorder primarily affecting boys, with symptoms typically appearing between ages 2 and 3. Early diagnosis through genetic testing is vital for accessing treatments, genetic counselling. Although there is no cure for Duchenne, ongoing clinical research and advancements in treatments like gene therapy are investigating ways to improve patient care and quality of life.