Magnetic Resonance Imaging and Biomarkers for Muscular Dystrophy
Magnetic Resonance Imaging and Biomarkers for Muscular Dystrophy
The purpose of this research study is to determine the potential of magnetic resonance
 imaging to monitor disease progression and to serve as an objective outcome measure for
 clinical trials in Duchenne Muscular Dystrophy (DMD). The investigators also hope to learn
 more about the changes that occur in muscles of the lower leg and arm in boys with DMD.

 The investigators will compare the muscles of ambulatory or non-ambulatory boys with DMD with
 muscles of healthy children of the same age and monitor disease progression in boys with DMD
 over a 5-10 year period. The amount of muscle damage and fat that the investigators measure
 will also be related to performance in daily activities, such as walking and the loss of
 muscle strength. In a small group of subjects the investigators will also assess the effect
 of corticosteroid drugs on the muscle measurements.
The overall objective of this proposal is to validate the potential of noninvasive magnetic
 resonance imaging (MRI) and spectroscopy (MRS) to monitor disease progression and to serve as
 an outcome measure for clinical trials in Duchenne muscular dystrophy (DMD). DMD is one of
 the most devastating genetically linked neuromuscular diseases and is characterized by the
 absence of dystrophin, resulting in progressive muscle weakness, loss of walking ability and
 premature death. Despite the poor prognosis for patients with muscular dystrophy, therapeutic
 interventions have been lacking, and outcome measures for clinical trials have been limited
 to measures of muscle function, serum biomarkers of muscle breakdown and invasive muscle
 biopsies. Additional quantitative outcome measures that are noninvasive and sensitive to
 changes in muscle structure and composition are needed to facilitate the rapid translation of
 promising new interventions from preclinical studies to clinical trials. As such, this
 proposal targets the development and validation of magnetic resonance as a noninvasive
 biomarker of disease progression in muscular dystrophy. Using a multi-site research design
 this study will examine the intramuscular lipid content, muscle damage/inflammation and
 contractile area in the lower extremity and/or upper extremity muscles of 200 ambulatory or
 non-ambulatory boys with DMD and 100 healthy age matched boys using a combination of MRI and
 MRS technologies. In order to assess the sensitivity of each MR measure to disease
 progression, all boys with DMD will be reevaluated in yearly or 6 month intervals. In
 addition, the investigators will correlate changes in MR measures with standard measures of
 disease progression, such as loss in muscle strength and functional ability. Using MRI/MRS
 the investigators will also examine the effect of initiating corticosteroid treatment on
 skeletal muscle characteristics and composition. Finally, the investigators will deposit
 immortalized fibroblasts from carefully characterized DMD boys participating in this study in
 established tissue repositories.

 The investigators anticipate that the MR techniques developed and validated in this proposal
 will be suitable for clinical trials in a wide range of muscular dystrophies and other
 neuromuscular diseases. In addition, MR characterization may serve as a powerful tool to
 further advance our understanding of the pathogenesis of muscular dystrophy and help guide
 the design of future trials.
Inclusion Criteria for boys with DMD:

 1. Ambulatory and non-ambulatory males (ages 5-18) previously diagnosed with DMD based
 on:

 -  clinical features with onset of symptoms before age five

 -  elevated serum creatine kinase level or

 -  absence of dystrophin expression, as determined by immunostain or western blot
 (<2%) and/or DNA confirmation of a dystrophin mutation.

 2. Subjects will not be excluded based on corticosteroid treatment

 Inclusion Criteria for age matched controls:

 1. Ambulatory males (ages 5-18) without disease or injury to the lower extremities

 Exclusion Criteria:

 1. Males with a contraindication to an MR examination

 2. Males with unstable medical problems

 3. Males who are not able to cooperate during testing

 4. Males with a secondary condition that may impact muscle metabolism, muscle function or
 functional ability (i.e. cerebral palsy, endocrine disorders, mitochondrial disease)

 5. Healthy boys who participate in competitive sports specific training in excess of 8
 hours per week. Participation in multiple recreational sports activities is not an
 exclusion.