Learn The BasicsDuchenne muscular dystrophy (DMD) is a rare neuromuscular disease mainly affecting boys. It is estimated that one in every 3600 baby boys are born with DMD worldwide.
The disease was first described by French neurologist Benjamin Amand Duchenne in 1860.
What causes DMD?
DMD is caused by a mutation in the DMD gene, which is located on the X chromosome. This gene codes for a protein called dystrophin, which stabilizes the cell membrane during muscle contraction.
The mutation in the DMD gene prevents the body from making functional dystrophin protein leading to muscle damage with movement that is slowly replaced with scar tissue over time.
Because boys only have one copy of the X chromosome, if they inherit the faulty gene from their mother, who is a carrier, they will develop DMD.
What are the symptoms of DMD?
The symptoms of DMD include an increase in the size of the calf muscle, difficulty climbing stairs, getting up from the floor and walking, which gets worse with time, walking on toes, a waddling gait, frequent falls and fatigue. As the disease progresses, patients lose the ability to walk altogether and require a wheelchair for mobility.
Patients may also have learning difficulties and cognitive impairment
In the later stages of the disease, as the heart muscle and muscles required for breathing such as the diaphragm get affected, patients need assistance with breathing and develop cardiomyopathy or heart muscle disease.
How do doctors diagnose DMD?
Diagnosing DMD starts with a medical history and physical examination.
An echocardiography or a cardiac magnetic resonance imaging test may also indicate abnormalities consistent with DMD.
Patients with DMD also have high levels of creatine kinase in their blood. This is an enzyme that is released from muscles that are damaged. However, this test is not specific as levels may also be elevated following strenuous exercise, for example.
A muscle biopsy may also help diagnose DMD, but this is rarely used.
A definitive diagnosis of DMD can be reached following a genetic test to look for mutations in the DMD gene if the disease is suspected based on the other test results.
How is DMD treated?
The first-line treatment for DMD is corticosteroid therapy. The aim of this treatment is to reduce inflammation and delay the progression of the disease. However, corticosteroids do not address the underlying cause of the disease and are associated with many unwanted side effects.
Patients may also benefit from physiotherapy and occupational therapy, but these cannot cure the disease.
Disease-modifying therapies for DMD are also available and may help treat patients with certain types of DMD.
One such therapy is called ataluren marketed under the brand name Translarna, which is suitable for patients whose disease is caused by a premature stop signal in the DMD gene. Translarna is approved in the European Union but not yet approved in the US.
There are also so-called exon-skipping therapies that aim to restore the reading frame of the DMD gene, which has been disrupted by mutations. These include eteplirsen (Exondys 51), golodirsen (Vyondys 53), casimersen (Amondys 45), and viltolarsen (Viltepso). Each of these is only suitable for patients with certain types of mutations in the DMD gene.
Finally, there is a gene therapy called delandistrogene moxeparvovec-rokl (Elevidys) approved for the treatment of boys with DMD, ages 4 to 5 that delivers a shorter copy of the DMD gene to the body that codes for a microdystrophin protein that is still smaller but functional.