To identify myotonic dystrophy type 1 (DM1) biomarkers through a comprehensive proteomic evaluation of cerebrospinal fluid (CSF) from patients.

Myotonic dystrophy type 1 (DM1), the most common adult form of muscular dystrophy, impacts muscle function, mobility, and leads to debilitating complications in multiple organ systems. It significantly affects patients quality of life and poses substantial challenges for healthcare providers in managing its multifaceted symptoms.

Proteomic analyses were conducted on CSF samples from DM1 patients (n=11) and healthy controls (n=5) using Olink monoclonal antibody panels. Lasso regression was employed in a supervised machine-learning analysis to identify proteins that differentiated DM1 and healthy control groups. Enrichment analyses using Reactome and KEGG databases identified specifically altered pathways.

This study represents the first exploratory CSF proteomic profiling of DM1 using the Olink panels, highlighting dysregulated protein pathways that may enhance our understanding of the disease development and inform future therapeutic strategies. For example, the proteomic evidence of altered IGF transport, in addition to the known mis-splicing of the insulin receptor in DM1, suggest that this important pathway, which is known to impact muscle growth, could underlie some aspects of muscle weakness and atrophy in myotonic dystrophy.  In addition to clarifying these dysregulated pathways in DM1, proteomic biomarkers can serve as diagnostic indicators, markers of disease activity, and measures of therapeutic response.