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

Inclusion criteria:

• 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 acharacteristic distribution, and history of similar findings in a first degreerelative. Genetic testing confirmed the diagnosis of DM1 in > 99% of individuals whosatisfied these criteria.2

Exclusion criteria:

• Symptomatic renal or liver disease, uncontrolled diabetes or thyroid disorder, oractive malignancy other than skin cancer.

• Current alcohol or substance abuse

• Concurrent enrollment in clinical trial for DM1, or participation in trial within 6months of entry.

• Concurrent pregnancy or planned pregnancy during the course of the study.

• Concurrent medical condition that would, in the opinion of the investigator orclinical evaluator, compromise performance on study measures.

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

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 cutsigns of limb weakness and muscle wasting. This is in order to obtain a muscletissue 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 3days 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 musclebiopsy in order to ensure that a sample taken would be of muscle and not just fatand fascia.

• Previous muscle biopsy of either TA in order to provide muscle tissue samples ofnon-biopsied muscles.