Defining Endpoints in Becker Muscular Dystrophy

Becker Muscular Dystrophy (BMD) is most frequently due to in-frame mutations in the dystrophin gene that are associated with reduced levels of frequently shortened dystrophin, though other mutations may be related to the Becker phenotype. There is wide variation in the age of onset and degree of progression, ranging from childhood to late adulthood. The more severe form of dystrophinopathy, Duchenne muscular dystrophy, has a more characteristic rate of progression and overall natural history. The wide variation in severity of progression has led to challenges in the design and conduct of approaching therapeutic trials. There is a need for a more rigorous natural history study to assist in the design of these promising therapeutic trials.

Inclusion criteria

For ages 6-12

• Clinically affected (defined as weakness on bedside evaluation in a pattern consistent with BMD)
• Genetic confirmation of an in-frame dystrophin mutation
• Ambulatory
• Willing and able to give informed consent and follow all procedures and requirements

For ages 13 and older

• Clinically affected (defined as weakness on bedside evaluation in a pattern consistent with BMD)
• Genetic confirmation of a dystrophin mutation
• Willing and able to give informed consent and follow all procedures and requirements

For participants in the MRI substudy:

• Ambulatory, defined as able to walk 10 meters without assistive devices (orthotics allowed)

Exclusion criteria

For ages 6-12

• Out of frame dystrophin mutation
• Use of chronic corticosteroids at baseline, defined as greater than 6 months of chronic use, will be limited to 20% of the overall population
• Non-ambulatory, defined as the inability to walk 10 meters without assistive device (excluding orthotics)
• >16 hours of ventilatory support
• Any other illness that would interfere with the ability to undergo safe testing or would interfere with interpretation of the results in the opinion of the site investigator.
• Under the age of 6 at time of enrollment
• For MR Cohort: Have contraindications to MRI or MRS (e.g., non-MR compatible implanted medical devices or severe claustrophobia)

For ages 13 and older

• Loss of ambulation prior to age 16
• Use of chronic corticosteroids, defined as greater than 6 months of chronic use, will be limited to 20% of the overall population
• Less than 30% of the overall population will be non-ambulatory, defined as the inability to walk 10 meters without assistive device (excluding orthotics)
• >16 hours of ventilatory support
• Subjects aged 13-16 only: time to rise >10 seconds
• For MR Cohort: Have contraindications to MRI or MRS (e.g., non-MR compatible implanted medical devices or severe claustrophobia)