An Ambispective Natural History Study in Myotonic Dystrophy Patients Linking Retrospective Data Captured From the DM-Scope Registry With a Prospective 24-month Follow-up Period

The rationale of the study is to gather longitudinal data on patients with DM1 and DM2 in order to better understand disease progression and evolution of myotonia and other symptoms and their associated complications/risks, particularly in relation to cardiac and other systemic manifestations. The primary objective is to investigate the evolution of myotonia presence, perception and its impact on the burden of disease over time in patients with Myotonic dystrophy type 1 (DM1) and type 2 (DM2). The secondary objective is to evaluate the progression of other DM-related multisystemic symptom manifestation such as cardiac, pulmonary, gastrointestinal (GI), hepatic, and renal impairments/disorders, muscle weakness, stumbling and falls in DM patients over 24-months. Additionally, the study will assess the use of pharmacological and non-pharmacological treatments for myotonia during the data collection period.

All of the patients will be recruited through the DM-Scope Registry. The registry database will be the source of the retrospective data to be used in the study. The study will begin with a detailed retrospective medical history assessment (up to -18 months to baseline) based on the annual routine DM-scope visits in the database. This will provide a comprehensive view of the patients' health status before the study. The 24-month prospective assessment period visits will occur at baseline, 12 months and 24 months. This approach allows for detailed tracking of disease progression and associated complications/risks over time.

The exploratory sub-study aims to broaden the understanding of DM1 pathophysiology by incorporating biophysical, functional, and behavioral measurements beyond traditional motor function and muscle strength. It also aims to evaluate the reliability of several innovative assessments, including advanced tools to deliver a multidimensional view of disease progression.

Inclusion criteria

• Enrolled in DM-scope registry genetically diagnosed with DM1 or DM2.
• Affiliation or beneficiary of a social security system or of such a regime.
• Ability to comprehend and willingness to sign an informed consent (ICF).
• Male or non-pregnant female ≥18 years of age at screening.
• Body Mass Index (BMI) of 18.5 kg/m2 to 30 kg/m2, and weight ≥45 kg.
• Medical history data covering up to 18 months prior to enrollment.
• Clinical sign of myotonia
• DM1 patients only - Muscular impairment rating scale (MIRS) score of 2, 3 or 4.
• Be able to walk independently 10 meters (cane, walker, orthoses allowed).

Exclusion criteria

• No informed consent.
• Pregnant or lactating women.
• Subjects benefiting from laws aimed at protecting vulnerable adults: subjects being deprived of liberty by judicial or administrative decision, subjects under guardianship /curatorship.
• Any medical condition or serious medical illness which in the opinion of the Investigator, precludes the participant's participation in the study or the participant is unlikely to comply with the protocol-defined procedures and therefore is unlikely to complete the study.
• Medical conditions that could affect hand functioning including (but not limited to) rheumatoid arthritis, Dupuytren's contracture, hand deformity, severe arthritis or any other medical condition (other than DM1/DM2) that would significantly impact ambulation.
• Patients with no documented record of myotonia assessment in the clinical records of the DM-scope database or myotonia absence at last visit prior to study enrolment.
• Not able to perform study specific performance tests and evaluations e.g. hand grip dynamometry, 10mWT, etc. (in the opinion of the investigator).
• Treatment with mexiletine within 18 months prior to baseline (Day 1).