Overview
A universal challenge in clinical investigation of novel therapeutics is the need for quantitative, objective biomarkers that directly address the mechanisms of disease and provide information relevant to clinically meaningful functional improvement. This has been a particular challenge in rare and slowly progressive diseases such as Duchenne Muscular Dystrophy (DMD).
The investigators hypothesize that urinary N-terminal fragment of titin (NTFT) corresponding to activity level/intensity will define a high-precision, non-invasive biomarker of systemic muscle injury to enable serial measurements of efficacy and safety in the clinical investigation of gene therapy for DMD and other myopathies. This should provide a valuable exploratory, secondary and eventually primary outcome measure of therapeutic efficacy to minimize the enrollment size in informative early phase and pivotal clinical trials.
Description
The investigators are recruiting ambulatory individuals with Duchenne Muscular Dystrophy (DMD) or Becker Muscular Dystrophy (BMD), and healthy volunteers.
At 3 regular clinical visits, participants will perform a descending stair walk down 2 flights of stairs. Urine will be collected before and after to measure how urinary N-terminal fragment of titin (NTFT) levels are impacted by the activity. Participants will also perform a standard battery of neuromuscular tests, including North Star Ambulatory Assessment and Timed Function Tests. These will be performed as part of the regular clinic visit. Participants will wear an activity monitor during all tests.
After both the first and second visits, participants will be sent home with an activity monitor to measure the participants activity over the course of 7 days. The participant's urine will be collected and frozen 3 times a day (morning, afternoon, and evening) during this period. The investigators will correlate physical activity intensity with the urinary NTFT (titin) levels and the severity of the disease (which will be based on the results of clinical neuromuscular tests).
If there is a clinically-indicated blood draw, participants will have the option to allow collection of an additional sample for exploratory analysis of additional biomarkers.
Eligibility
DMD/BMD Subject Inclusion/Exclusion Criteria
Inclusion Criteria:
- Ambulatory at screening
- Genetically confirmed diagnosis of DMD/BMD
- Parental/guardian permission (informed consent) for children. Child assent will also be obtained from patients ages 7 years old and older and deemed by the investigator to be neurodevelopmentally appropriate
- Access to electricity and a freezer in the home, in order to utilize the provided device and store collected samples
Exclusion Criteria:
- Non-ambulatory at Screening, defined as unable to walk independently and needing assistive devices
- Female patients
- Parental/guardian unable to provide informed consent
Healthy Control Subject Inclusion/Exclusion Criteria
Inclusion criteria:
- Healthy children without DMD, BMD, or other significant chronic medical disease
- Ambulatory at Screening, defined as able to walk independently without assistive devices
- Parental/guardian permission (informed consent). Child assent will also be obtained from patients aged 7 years and older and deemed by the investigator to be neurodevelopmentally appropriate.
- Access to electricity and a freezer in the home, in order to utilize the provided device and store collected samples
Exclusion criteria:
- Non-ambulatory at Screening, defined as unable to walk independently and needing assistive devices
- Female patients
- Parental/guardian unable to provide informed consent