Duchenne Muscular Dystrophy disease mechanism in adults
Duchenne Muscular Dystrophy (DMD) is a severe genetic disorder characterized by progressive muscle degeneration and weakness. While it is most often diagnosed in childhood, understanding its disease mechanism in adults is crucial for managing long-term health and improving quality of life. DMD is caused by mutations in the dystrophin gene, which encodes a critical structural protein called dystrophin. This protein acts as a shock absorber, providing stability to muscle cell membranes during contraction. Without functional dystrophin, muscle fibers become increasingly fragile and susceptible to damage.
The absence or deficiency of dystrophin leads to a cascade of pathological events within muscle tissue. In early stages, muscle fibers undergo repeated cycles of injury and repair. However, as the disease progresses, the repair process becomes overwhelmed, and muscle tissue is gradually replaced by fibrous connective tissue and fat. This replacement results in the loss of muscle mass and strength, affecting various muscle groups throughout the body. In adults with DMD, this process is often compounded by the cumulative effects of years of muscle degeneration.
A key aspect of DMD’s disease mechanism in adults is the persistent inflammation within affected muscles. Damaged muscle fibers release signals that attract immune cells, leading to chronic inflammation. This inflammatory response, although initially aimed at repairing tissue, can further exacerbate muscle damage. Over time, the ongoing cycle of injury and inflammation fosters a hostile environment that impairs muscle regeneration and accelerates disease progression.
Another significant factor in adult DMD pathology is the imbalance of calcium homeostasis within muscle cells. Damaged membranes allow excess calcium ions to enter the cells, activating enzymes that degrade cellular components and promote cell death. Elevated calcium levels also contribute to mitochondrial dysfunction, reducing the energy supply necessary for muscle maintenance and repair. As mitochondria become compromised, muscle cells lose their ability to sustain normal function, contributing to further weakness and degeneration.
In adults, secondary complications arise from the progressive loss of muscle function. Respiratory and cardiac muscles are particularly vulnerable, leading to issues such as respiratory insufficiency and cardiomyopathy. These complications are often the primary causes of mortality in adult DMD patients. Additionally, skeletal deformities like scoliosis can develop due to weakened stabilizing muscles, further impairing mobility and respiratory capacity.
Current management strategies focus on slowing disease progression, addressing symptoms, and maintaining function. Corticosteroids are commonly used to reduce inflammation and delay muscle deterioration. Emerging therapies aim to restore dystrophin expression or compensate for its absence through gene therapy, exon skipping, and other molecular approaches. Physical therapy and assistive devices are vital in preserving mobility and independence, while vigilant monitoring of cardiac and respiratory health is essential for comprehensive care.
Understanding the disease mechanism in adults with DMD underscores the importance of early intervention and ongoing management. Though there is no cure yet, advances in research continue to bring hope for improved therapies that can modify the disease course and enhance the quality of life for those affected.
