Myotonic Dystrophy type 1 (DM1) is an autosomal dominant genetic disorder caused by an expansion of trinucleotide cytosine-thymine-guanine (CTG) repeat mutation. It has a prevalence of 9.27 per 100,000 globally and causes progressive muscle weakness; however, other multiorgan systems are involved such as gastrointestinal, cardiac, endocrine, and central nervous system (CNS). The CNS involvement is not fully understood and requires further investigation. This study aims to characterize molecular changes through post-mortem brain samples, as well as both functional metrics and biomarkers in those living with DM. While distinct from the primary objectives, this study leverages the concurrent Myocap investigation by facilitating recruitment for the validation of wearable-derived kinematic biomarkers in DM1 representing a comprehensive approach to capturing the characteristic multi-organ impacts of DM1.
Through standardized clinical procedures and longitudinal sample collection, the study aims to characterize CNS involvement and identify potential digital and fluid biomarkers of disease progression. Recruitment will target 20 participants with DM1 and 10 unaffected controls, ages 18-80 years old. Participants will undergo comprehensive neuropsychological testing administered by a trained staff member or Neuropsychologist followed by computerized cognitive assessments using the NIH-toolbox. Participants will also complete a standardized 25-minute resting state EEG (eyes open and closed) and a 30-minute active state EEG during the NIH-toolbox testing, using Zeto WR19 wireless EEG system (Zeto Inc., USA). Study procedures also include a blood draw, safety labs, brain MRI including fMRI and DTI, physical exam, and a lumbar puncture to collect CSF samples. By integrating longitudinal clinical, digital, and molecular data, this study establishes a robust framework for identifying sensitive biomarkers and validating outcome measures essential for the advancement of targeted therapeutic trials in DM1.