Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary muscle disorder that affects approximately 1 in 20,000 individuals. Although there has been progress in elucidating the mechanisms of disease in FSHD, the translation of this knowledge into effective therapies is impeded by limited information on the natural history of disease and a lack of appropriate disease biomarkers. MRI is a promising tool in the assessment of subclinical disease in skeletal muscle, and we hypothesize that it is a better predictor of changes in disease severity than the current outcome measures used in studies of muscular dystrophy. The 3 specific aims of the proposed research will use non-invasive MRI techniques to prospectively study the progression of disease in FSHD and develop imaging-based biomarkers for future clinical research.
Specific Aim 1 : To prospectively evaluate the radiographic progression of disease in FSHD using morphologic whole-body MRI. The prospective design of this longitudinal cohort study will allow us to test our hypothesis that whole-body T1-weighted and short-tau inversion recovery MRI sequences will detect clinical and subclinical disease progression in individual muscles over 2 years in subjects with FSHD.
Specific Aim 2 : To characterize early disease-related changes in normal-appearing muscle using novel metabolic imaging techniques in adolescent and young adult subjects with FSHD. We hypothesize that we will be able to detect metabolic abnormalities within muscles that appear normal on traditional MRI sequences using diffusion-weighted imaging and magnetic resonance spectroscopy.
This aim i s unique in its utilization of the pediatric FSHD population, which will provide valuable insight into the pathological processes that occur at the time of symptom onset.
Specific Aim 3 : To compare MRI-based biomarkers to clinical outcome measures in muscular dystrophy. As the most widely-used outcome measures in muscular dystrophy research are clinical outcome measures (strength and timed function tests), we will compare imaging-based biomarkers obtained using whole-body MRI to clinical outcome measures in a large cross-sectional sample of subjects with FSHD. We anticipate that MRI will prove to be a superior and more objective predictor of function in FSHD. Our proposed research will utilize a muscle-specific MRI protocol to characterize in detail longitudinal changes in the radiographic phenotype of FSHD. This information will be used to develop quantitative, non- invasive outcome measures that are needed for clinical trials and observational studies in muscle disease. We anticipate that the combination of metabolic and morphologic MRI sequences will not only become valuable disease biomarkers, but will provide a new gold standard for the validation of future genetic and epigenetic biomarkers of disease in FSHD.

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The proposed research will investigate the longitudinal progression of muscle disease in facioscapulohumeral muscular dystrophy using whole-body MRI sequences. This data will be used to develop non-invasive imaging biomarkers and surrogate outcome measures for future clinical trials and observational studies in muscular dystrophy and other skeletal muscle diseases.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Mentored Patient-Oriented Research Career Development Award (K23)
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Neurological Sciences Training Initial Review Group (NST)
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Nuckolls, Glen H
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Hugo W. Moser Research Institute Kennedy Krieger
United States
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Leung, Doris G (2018) Magnetic resonance imaging in facioscapulohumeral muscular dystrophy. Muscle Nerve 57:872-874
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