Biomarkers in rare neuromuscular diseases

Duchenne muscular dystrophy (DMD) is a severe, X-linked disease, affecting 1:5000 males, and characterized by progressive muscle weakness and muscle mass loss in children. Genetic and biochemical research over the years has led to the characterization of the genetic cause and pathophysiology of the disease. Moreover, the elucidation of genetic mechanisms underlining Duchenne muscular dystrophy has allowed the design of innovative personalized molecular therapies. The identification of specific, accurate, and sensitive biomarkers is becoming crucial for evaluating muscle disease progression and response to therapies, for disease monitoring, and to accelerate drug development and related regulatory processes. Several exploratory biomarkers have been discovered by analyzing DMD patients' cohorts and provided clues about tissue or fluid proteins and RNA biomarkers (Table 1), as well as allowed the identification of SNPs acting as DMD genetic modifiers (Table 2). Nevertheless, challenges were encountered in translating biomarkers into the clinical context and many bottlenecks still exist, hampering their adoption as surrogate endpoints. These issues could be overcome by national and international collaborative efforts, multicenter data sharing, and by the creation of large cohorts of patients as well as by the application of novel statistical tools, that can be effective also when patient numbers are small. Being DMD a Mendelian disease, building up “biomarker heatmaps” might help making multiple biomarkers applicable to clinical practice and possibly to clinical trials.