Comprehensive five-year disease progression assessment of DM1, based on the Dutch MYODRAFT registry

Myotonic Dystrophy type 1 (DM1) is a slowly-progressive, multi-system disorder affecting skeletal, cardiac and smooth musculature amongst other tissues, leading to decrement in daily and social activities and reduced quality of life expectations. Currently, no treatment is available, and disease management largely focusses on symptom management and detecting organ complications in early stages. Fortunately, significant advancements in understanding the complex pathophysiology have led to promising treatments targeting disease mechanisms in preclinical trials. However, current clinical trial design in DM1 is limited by a lacking consensus about the selection of outcome measures and by inadequately taking disease progression into account. To overcome these challenges, a longitudinal study was initiated as part of the routine assessment of DM1 patients (MYODRAFT), conducted by Maastricht University Medical Centre+ and Radboud University Medical Centre, together the national DM1 expertise centre of the Netherlands. The present study aims to capture long-term disease progression through the concept of predefining clinically relevant changes, as well as identifying relevant outcome measures to be used in clinical trials. This analysis will provide an overview of disease progression in 500 participants, and identifies the natural course of the disease within multiple domains in a five-year period. Furthermore, these results will aid in the selection of appropriate outcome measures and thereby pave the way forward to trial-readiness. Myotonic Dystrophy type 1 (DM1) is a slowly-progressive, multi-system disorder affecting skeletal, cardiac and smooth musculature amongst other tissues, leading to decrement in daily and social activities and reduced quality of life expectations. Currently, no treatment is available, and disease management largely focusses on symptom management and detecting organ complications in early stages. Fortunately, significant advancements in understanding the complex pathophysiology have led to promising treatments targeting disease mechanisms in preclinical trials. However, current clinical trial design in DM1 is limited by a lacking consensus about the selection of outcome measures and by inadequately taking disease progression into account. To overcome these challenges, a longitudinal study was initiated as part of the routine assessment of DM1 patients (MYODRAFT), conducted by Maastricht University Medical Centre+ and Radboud University Medical Centre, together the national DM1 expertise centre of the Netherlands. The present study aims to capture long-term disease progression through the concept of predefining clinically relevant changes, as well as identifying relevant outcome measures to be used in clinical trials. This analysis will provide an overview of disease progression in 500 participants, and identifies the natural course of the disease within multiple domains in a five-year period. Furthermore, these results will aid in the selection of appropriate outcome measures and thereby pave the way forward to trial-readiness.