Muscular Dystrophy (MD) is a group of genetic disorders that cause progressive weakness and degeneration of skeletal muscles. MD is classified as a neuromuscular disease (NMD), placing it among conditions that impair the function of muscles or the nerves that control them. While symptoms manifest as profound muscle weakness, the underlying biological defect is a primary issue within the muscle fibers themselves. Inherited mutations interfere with the production of proteins necessary to maintain healthy muscle structure. This progressive degeneration leads to the gradual loss of muscle mass, which is often replaced by fat and fibrotic tissue.
Defining Neuromuscular Diseases
Neuromuscular diseases (NMDs) affect the entire motor unit, the system responsible for voluntary movement. The motor unit includes nerve cells in the spinal cord, peripheral nerves, and the skeletal muscles they innervate. Dysfunction in any of these three components—the nerve, the connection point, or the muscle—results in an NMD diagnosis. MD specifically falls under myopathies, which are NMDs involving primary damage to the muscle fiber itself. Unlike conditions such as Amyotrophic Lateral Sclerosis (ALS), MD is a muscle-based disorder where the nerves remain intact, but the muscle tissue cannot maintain its integrity.
The Role of Dystrophin
Dystrophin Function
MD’s classification as a myopathy is understood by examining the function of Dystrophin, the protein affected in the most common forms of the disease. Dystrophin is a large protein that acts as a structural link, connecting the muscle fiber’s internal cytoskeleton to the extracellular matrix through the cell membrane (sarcolemma). It functions as a molecular shock absorber, stabilizing the muscle membrane during contractions and stretches.
Consequences of Dystrophin Deficiency
When the Dystrophin gene is defective, the resulting protein is non-functional or absent. Without this stabilizing linkage, the sarcolemma becomes fragile and susceptible to mechanical damage with every muscle contraction. Repeated tears trigger a cycle of damage, inflammation, and attempted repair. Eventually, the muscle tissue’s capacity for regeneration is overwhelmed, and damaged fibers are replaced by non-functional fibrotic and fatty tissue. Dystrophinopathies, the most common forms of Dystrophin-related MD, follow an X-linked inheritance pattern, primarily affecting males.
Key Forms of Muscular Dystrophy
Duchenne and Becker MD
Muscular Dystrophy is a group of genetic disorders, each with varying severity and age of onset. Duchenne Muscular Dystrophy (DMD) is the most frequently diagnosed form in childhood, characterized by the near-complete absence of functional Dystrophin. Symptoms typically begin around four years of age, leading to difficulty standing or climbing stairs. DMD is rapidly progressive, with most affected individuals requiring a wheelchair by their early teens.
Other Forms of MD
Becker Muscular Dystrophy (BMD) is related to DMD, but the mutation allows for the production of a partially functional, shortened Dystrophin protein. This partial function results in a milder clinical course and later onset, often beginning in the teens or adulthood. Progression is slower in BMD, and patients often retain the ability to walk into adulthood. The spectrum also includes Limb-Girdle Muscular Dystrophy (LGMD), which primarily affects the muscles around the hips and shoulders. LGMD is caused by defects in other proteins, such as the sarcoglycans, leading to muscle fiber degeneration with varying patterns of weakness.
Approaches to Managing Muscular Dystrophy
Standard Care and Pharmacological Treatment
While no cure exists, management focuses on maximizing quality of life, maintaining mobility, and slowing disease progression. Standard care involves a multidisciplinary approach, including physical and occupational therapy to maintain joint flexibility and prevent contractures. Orthopedic interventions, such as bracing and corrective surgery for scoliosis, support function and posture. Corticosteroids, such as Prednisolone or Deflazacort, are used for Duchenne MD to slow muscle degeneration and prolong ambulation.
Cardiac, Respiratory, and Emerging Therapies
Proactive monitoring and management of cardiac function and respiratory support are integrated into long-term care, as the heart and respiratory muscles are also affected. Non-invasive positive pressure ventilation addresses breathing difficulties as muscle weakness progresses. Emerging therapies focus on correcting the underlying genetic defect to restore Dystrophin production. Exon skipping agents, such as Golodirsen and Viltolarsen, use synthetic molecules to encourage the cell’s machinery to skip defective parts of the Dystrophin gene, resulting in a shortened but functional protein. Gene therapy approaches, which deliver a micro- or mini-Dystrophin gene directly to muscle cells using viral vectors, are also under active investigation.