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A Prospective Longitudinal Observational Study in Myotonic Dystrophy Type One: From Clinical Outcomes to Trial Design (P8-9.003)
Abstract   Peer reviewed

A Prospective Longitudinal Observational Study in Myotonic Dystrophy Type One: From Clinical Outcomes to Trial Design (P8-9.003)

Valeria Sansone, Carola Ferrari Aggradi, Andrea Lizio, Michela Nani, Jeanne Dekdebrun, Katy Eichinger, Cynthia Gagnon, S Subramony, Richard Roxburgh, Johanna Hamel, …
Neurology, Vol.106(11_Supplement_1)
06/09/2026
DOI: 10.1212/WNL.0000000000215044

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Abstract

Objective The END-DM1 study is an international prospective longitudinal study involving adult with DM1 to establish biomarkers and clinical endpoints using harmonized protocols and procedures. Here we seek to determine the burden of disease and select endpoints for clinical trials. Background Myotonic dystrophy type 1 (DM1) is among the most variable of diseases, with a wide range of disease burden. Large cohorts are required to assess the variable disease burden to determine appropriate endpoints for clinical trials and to standardize trial site processes. Design/Methods Individuals with DM1 who were older than 18 were enrolled in a 24-month observational study. Measures of cognition, quantitative muscle strength, motor function (e.g., 10 MWT, 6 MWT), myotonia, cardiac arrhythmias, pulmonary function, and quality of life were collected. The medical history and age of onset were collected at baseline. A subset of the cohort had muscle biopsies to assess the degree of RNA mis-splicing. Results 700 adults with DM1 were enrolled and the baseline results are presented here. The mean age of the participants was 44 years old, and the mean age of onset was 25. Of the participants, 0.33% were non-ambulatory. Strong associations were identified between measures of muscle strength and motor function, while weak associations were identified with myotonia. The cohort had a wide range of performance on the cogstate, a measure of cognition, with some performing above average. Approximately 1/3 of the cohort had arrhythmias identified on the electrocardiogram. Conclusions The Myotonic Dystrophy Clinical Research Network (DMCRN) proves to be a valid framework to collect clinical and demographic data from a large international cohort of adults with DM1. It allows to compare differences between cohorts and to identify potential fast progressors and most sensitive outcomes that may need to be accounted for in the design of future clinical trials.

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