Establishing Biomarkers and Clinical Endpoints in Myotonic Dystrophy Type 1 (END-DM1) Extension

Establishing Biomarkers and Clinical Endpoints in Myotonic Dystrophy Type 1 (END-DM1) Extension

Myotonic Dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder that causes progressive disability and shortened life expectancy. It is characterized by progressive weakness and myotonia, which preferentially affects the craniofacial, hand, and distal leg muscles. Many patients also experience difficulties with cognition, cardiac arrhythmias, respiratory failure, or cataracts. Currently there is no treatment to slow progression or reverse the symptoms.

The goal of this observational study is to characterize long-term disease progression over at least 4 years in at least 1,000 adults with myotonic dystrophy type 1 (DM1).

The main questions this study aims to answer are:

1. How do clinical measures, such as walking speed, hand function, and muscle strength, change over a multi-year period in people with DM1?
2. Can long-term changes in slowly progressive measures, like heart rhythms (ECG) and lung function (FVC), be accurately captured and used as biomarkers for the disease over time?

Inclusion Criteria:

• Age 18 to 70 years (inclusive)
• Written, voluntary informed consent must be obtained prior to any study procedures. In cases where a Legally Authorized Representative (LAR) provides consent, verbal assent will be obtained from the subject, as determined by the investigator and documented directly on the consent form. Capacity to consent will be determined by the neurologist at the Baseline visit and will be signed off on the Inclusion/Exclusion checklist.
• Clinical diagnosis of DM1 based on research criteria or positive genetic test. The research criteria for clinical diagnosis of DM1 require myotonia, muscle weakness in a characteristic distribution, and history of similar findings in a first degree relative. Genetic testing confirmed the diagnosis of DM1 in > 99% of individuals who satisfied these criteria. OR A diagnosis of CDM, which is defined as children having symptoms of myotonic dystrophy in the newborn period (<30 days), such as hypotonia, feeding or respiratory difficulty, requiring hospitalization to a ward or to the neonatal intensive care unit for 3 days or more; and a genetic test suspicious of an expanded trinucleotide (CTG) repeat in the DMPK gene in the child or first degree relative. An expanded CTG repeat size in the child is considered greater than 200 repeats or E1-E4 classification (E1= 200-500, E2=500-1,000, E3=1,000-1,500, E4>1,500)

Exclusion Criteria:

• Symptomatic renal or liver disease, uncontrolled diabetes or thyroid disorder, or active malignancy other than in situ skin cancer.
• Current alcohol or substance use disorder.
• Concurrent pregnancy or planned pregnancy during the course of the study.
• Concurrent medical condition that would, in the opinion of the investigator or clinical evaluator. compromise performance on study measures.
• Use of mexiletine or other anti-myotonia agents within 72 hours of any study visit.