Current biomarker development in myotonic dystrophies

Myotonic dystrophies (DM) are autosomal dominant, multisystemic disorders characterized by myotonia and progressive muscle weakness. Extramuscular multisystem symptoms include involvement of the respiratory, cardiac and central nervous systems, and endocrine and autoimmune alterations. While there is significant overlap in key symptoms due to a shared molecular backbone of alternative splicing, DM1 and DM2 differ in genetic origin, disease progression, and aspects of molecular pathology. Currently, DM management focuses on symptoms, and the wide clinical variation leads to long diagnostic delay. This highlights the need for reliable biomarkers to aid diagnosis, prognosis, and monitoring. As the understanding of molecular mechanisms in DM improves, new therapies are rapidly emerging, further emphasizing the need for reliable biomarkers to assess short- and long-term treatment efficacy. This review covers current biomarker research, including imaging-based, muscle-derived, and soluble liquid biopsy approaches. While established DM biomarkers are limited, with research disproportionately focused on DM1, multiple markers of alternative splicing pathology show promise. However, their reliance on invasive sampling restricts cohort size and longitudinal assessment. Consequently, efforts are shifting toward developing minimally invasive biomarkers. While some soluble markers, like muscle-specific circulating microRNAs, correlate with clinical measures, inconsistent detection, and limited evaluation of disease specificity point to the need for further research in larger, more diverse longitudinal cohorts. Future progress will depend on validating existing candidates, discovering new biomarkers addressing these limitations, and reducing the imbalance between DM1- and DM2-focused research to advance DM diagnosis, management, and therapy development.