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

Open to people ages 18-70

• Age 18 to 70 (inclusive)
• Competent to provide informed consent
• Clinical diagnosis of DM1 based on research criteria1 or positive genetic test
• Comment: The clinical research criteria 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.2

• Symptomatic renal or liver disease, uncontrolled diabetes or thyroid disorder, or active malignancy other than skin cancer.
• Current alcohol or substance abuse
• Concurrent enrollment in clinical trial for DM1, or participation in trial within 6 months of entry.
• 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.

• Note: non-ambulatory participants are not excluded, but are limited to <15% of enrollment.

  Inclusion criteria for participants in the muscle biopsy sub-study: • Of the 95 patients undergoing the tibialis anterior muscle biopsy, at least half will have at least moderate weakness of ankle dorsiflexion, defined as MRC score ≤ 4+. This is in order to obtain a muscle tissue sample in a person more severely affected with myotonic dystrophy. Approximately 10 patients at each site will undergo the muscle biopsy. Exclusion criteria for 95 participants in the muscle biopsy sub-study:

• Known CTG repeat expansion size less than 100 repeats, unless there are clear cut signs of limb weakness and muscle wasting. This is in order to obtain a muscle tissue sample in a person more severely affected with myotonic dystrophy.
• Use of anticoagulant such as warfarin or a direct oral anticoagulant (e.g. dabigatran) due to the increased risk of bleeding.
• Use of aspirin or non-steroidal anti-inflammatory agents should be discontinued 3 days prior to the biopsy procedure, if possible.
• Platelet count <50,000 (if known) due to the increased risk of bleeding.
• History of a bleeding disorder due to the increased risk of bleeding.
• Advanced wasting of tibialis anterior (TA) muscle that precludes needle muscle biopsy in order to ensure that a sample taken would be of muscle and not just fat and fascia.
• Previous muscle biopsy of either TA in order to provide muscle tissue samples of non-biopsied muscles.