Development of Quantitative Muscle Imaging as a Biomarker of Disease Endpoints in Myotonic Dystrophy

Development of Quantitative Muscle Imaging as a Biomarker of Disease Endpoints in Myotonic Dystrophy (DeQoDE-DM)

Myotonic dystrophy (dystrophia myotonica; DM), the most prevalent form of muscular dystrophy in adults, is characterized by progressive myopathy, myotonia, and multi-systemic involvement. DM causes severe disability and profoundly affects the patient's quality of life. Currently, no effective treatments are available that alter the course of the disease, but ongoing clinical trials are underway.

Past and current clinical trials in DM1 have relied on muscle biopsies to evaluate pathology and measure drug activity. However, this method is invasive and inefficient for long-term monitoring. What is lacking are non-invasive imaging biomarkers capable of providing comparable data, which would enhance trial planning, accelerating drug development while reducing morbidity and costs. Non-invasive muscle imaging, particularly through Quantitative Magnetic Resonance Imaging (qMRI), is essential to better understand how DM affects muscle structure. Moreover, the relationships between Magnetic Resonance Imaging (MRI) measures, disease severity, and Ribonucleic Acid (RNA) splicing outcomes from muscle tissues in the same DM patients are not yet known. As MRI has been relatively unstudied in DM, there needs to be a comprehensive baseline characterization of muscle structure and its relationship to clinical endpoints and RNA-associated disease processes. This will help evaluate the potential of qMRI as a biomarker of disease severity in DM.

Inclusion Criteria:

DM subjects

• Age 18 - 65 years
• Diagnosis of DM1 or DM2 by clinical or genetic criteria. If DM1 or DM2 was diagnosed by clinical criteria, a first-degree relative must have genetic testing confirmation and sign a genetic consent form to release their genetic information
• Clinically affected, as defined by muscle weakness or myotonia
• Ambulate independently (a walker is not permitted)
• Able to provide informed consent for participation in the study

Control subjects

• Age 18 - 65 years old
• Healthy as defined by no significant medical or neurological conditions
• Able to provide informed consent for participation in the study

Exclusion Criteria:

• Cardiac pacemaker, defibrillator, metal implants, or other contraindications for MRI
• Use of anabolic or catabolic agents within one year of entry
• History of lumbar spine or leg surgery, lumbar radiculopathy, or peripheral neuropathy
• BMI > 35 because obesity compromises positioning on the MR scanner
• Pregnancy
• For muscle biopsy, history of bleeding disorders or on anticoagulation. Subjects taking nonsteroidal anti- inflammatory agents will be asked to discontinue these medications 7 days prior to muscle biopsy.