Duchenne Muscular Dystrophy (DMD)
What is Duchenne Muscular Dystrophy?
Duchenne Muscular Dystrophy (DMD) is a progressive genetic neuromuscular disorder primarily affects males. It is the most common type of muscular dystrophy with one in 3,500 new born males developing DMD worldwide. Females inherit the defective gene and pass it on, thereby serving as carriers. The average age of diagnosis is 5 years.
Cause of DMD: The missing muscle protein
DMD is causes by a genetic mutation in the DMD gene, located on the X chromosome, that prevents the body to produce the protein dystrophin. More than 2000 mutations have been identified in people with DMD. This protein is very important for normal muscle function. It plays a critical role in protecting and strengthening the muscle fibers during normal muscle contraction and relaxation cycles. In the absence of dystrophin, the muscle fibers suffer progressive and irreversible damage from repeated contractions.
Signs and symptoms of DMD
The primary sign of DMD is muscle weakness. Symptoms can begin as early as ages 3 to 5, with muscle weakness in the upper arms and legs and then spreading to the heart, lungs, throat, stomach, intestines, and spine. Affected children find it difficult to walk run or jump. Other symptoms include enlargement of the calf muscle, a waddling gait while walking and an inward curve of the spine (lumbar lordosis). As the disease progresses, the heart muscle and muscles that help breath begin to weaken leading to more serious health problems. By adolescence, most males with DMD are unable to walk and require wheelchair assistance and a respirator to breath.
What treatment options are available?
Treatment of DMD requires a multidisciplinary approach, involving neuromuscular, cardiac, respiratory, endocrinological, nutritional, psychosocial, and orthopedic care management teams. FDA approved medications are also available to alleviate symptoms and prolong and improve the quality of life. Medications used to treat DMD include corticosteroids, gene therapy, exon skipping drugs and therapies that promote growth and regeneration. Most of the new therapies work by either restoring or replacing the dystrophin protein, reducing inflammation in the damaged muscles, or boosting the regenerative capability of the muscle cells. Corticosteroids such as prednisone, deflazacort, and vamoralone are most commonly prescribed to patients with DMD to slow down the progression of muscle weakness and delay the loss of walking ability.
Patients considering gene replacement or exon skipping therapies must undergo genetic testing to be considered. The goal with these therapies is to convert DMD to a milder form of muscular dystrophy. Elevidys is the first gene therapy drug approved for DMD. This drug uses a modified virus to deliver a modified dystrophin gene into the cells. The body in turn produces a shortened version of dystrophin, thereby restoring its function. Exon skipping therapy drugs include Amondys 45, Viltepso, Vyondys 53, Exondys 51. These drugs work by skipping over a section of the gene called exon to avoid the DMD mutation leading to the production of a truncated but functional dystrophin.
Conclusion
With the advancement of science, improved standard of care involving multidisciplinary teams, availability of disease-modifying treatments, and better cardiac and respiratory support patients with DMD live beyond their teens into 30’s and 40’s.
Sources:
Assessed and Endorsed by the MedReport Medical Review Board
