Drugdu.com expert's response:

Glucocorticoids (such as prednisone and deflazacort) are the standard therapeutic drugs for Duchenne muscular dystrophy (DMD), primarily due to their well-established efficacy in delaying disease progression, improving motor function, and prolonging survival. Their mechanisms of action also align closely with the pathological features of DMD. Below is a detailed analysis of the reasons:

The only disease-modifying drugs validated by evidence-based medicine

Prolonged motor capacity: Multiple studies have demonstrated that glucocorticoids significantly delay the decline in motor function in DMD patients. For example:

Children treated with prednisone exhibit superior muscle strength compared to untreated counterparts, with independent walking duration extended by over three years.

Deflazacort treatment delays the age at which children lose ambulation by 1.4-2.5 years, increases the 6-minute walk distance, and improves pulmonary function.

Delayed complications: Glucocorticoids reduce the risk of scoliosis (11.6% in the treatment group vs. 33.2% in the untreated group), postpone the onset age of cardiomyopathy, and decrease the duration of ventilator dependence.

Prolonged survival: The average survival of DMD patients receiving long-term glucocorticoid therapy can be extended to over 30 years, whereas untreated patients often succumb to respiratory or cardiac failure before the age of 20.

Mechanisms of action highly compatible with DMD pathology

DMD is caused by mutations in the dystrophin gene, leading to a deficiency of the protective protein dystrophin in muscle cells, which renders them susceptible to inflammatory damage. Glucocorticoids exert protective effects through multiple pathways:

Anti-inflammatory action: Inhibit the NF-κB pathway, reduce the release of inflammatory cytokines, and alleviate muscle fibrosis.

Immunomodulation: Decrease lymphocyte activity and mitigate autoimmune attacks on muscle tissue.

Promotion of muscle repair: Stimulate the secretion of insulin-like growth factor-1 (IGF-1), enhance myoblast proliferation, and increase muscle mass.

Stabilization of cell membranes: Reduce calcium ion influx and lower the risk of muscle cell necrosis.

Balance between long-term efficacy and safety

Despite the potential side effects of glucocorticoids (such as weight gain, osteoporosis, and delayed growth and development), their efficacy significantly outweighs the risks:

Efficacy advantages: Compared to untreated patients, glucocorticoid therapy can maintain muscle strength for an additional 2-5 years and significantly delay disease progression.

Side effect management: Side effects can be effectively controlled through dose adjustments (e.g., high-dose weekend therapy), combination therapy (e.g., calcium and vitamin D supplementation), and regular monitoring. For example:

Deflazacort is superior to prednisone in terms of weight gain and behavioral side effects but requires monitoring for osteoporosis risk.

Prednisone is associated with lower risks of height suppression and cataracts, making it suitable for long-term use.

Recommendations from international guidelines and consensus in clinical practice

American Academy of Neurology (AAN): Lists prednisone as a B-level evidence-based drug for improving muscle strength and pulmonary function in DMD and a C-level evidence-based drug for reducing the need for scoliosis surgery.

European Neuromuscular Centre (ENMC): Explicitly identifies glucocorticoids as first-line therapy for DMD and recommends initiating treatment at the age of 3-5 years.

Chinese expert consensus: The use rate of glucocorticoids among DMD children in China is only 35.2% (significantly lower than the international rate of 60%), highlighting the urgent need for increased awareness.

Irreplaceability compared to other therapeutic strategies

Gene therapy: Although exon-skipping therapies (such as EXONDYS 51) can restore partial dystrophin function, they are only applicable to specific mutation types, and their efficacy remains incompletely defined.

Stem cell therapy: Still in the experimental stage, with a lack of long-term safety data.

Supportive care: Modalities such as rehabilitation training and respiratory support can only alleviate symptoms and cannot delay disease progression.

Conclusion

Glucocorticoids delay the pathological progression of DMD through multi-targeted effects, with their efficacy validated by large-scale global clinical trials. They offer operational feasibility and cost-effectiveness advantages. Despite potential side effects, these risks are manageable through individualized dose adjustments and comprehensive management. Therefore, glucocorticoids remain the cornerstone of standard DMD therapy, providing patients with a valuable treatment window until more effective gene therapies or disease-modifying drugs become available.