Research in Congenital Muscle Disease

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Over the past year, I continued as an Assistant Clinical Investigator in the Tissue Injury Branch of the NINR, a position I started in September of 2012. Over the past year, I have enrolled participants in two active protocols. The first one is a study to develop the first proxy motor outcome assessment in young children with neuromuscular disease, entitled Development of a Proxy Motor Outcome Measure in Young Children with Neuromuscular Disease. Eighteen parents (or legal guardians) were enrolled and were interviewed by phone using qualitative methods. These results were then analyzed and the major themes were presented to a focus group of 10 experts in pediatric neuromuscular disease. The next step is for the focus group comments to be incorporated into the development of specific items for this novel scale of proxy reported motor function in young children age birth through 5 years. The goal is to use the new scale in future clinical trials to decrease parent stress related to travel to research centers for clinical trials and to improve ecological validity of motor function by utilizing parent insight in the home setting. My team also enrolled 32 pediatric participants and 29 parents in the active second protocol, The Calibration and Validation of the PROMIS and Neuro-QOL Questionnaires in Cerebral Palsy and Congenital Muscular Dystrophy. Preliminary item response theory analyses are underway with Columbia University, the collaborating institution, to validate these two questionnaires for use in neuromuscular disease patients. A third study received the Bench to Bedside Award this past year and is currently under IRB review. This is a clinical trial of antioxidant therapy in patients with RYR1 congenital myopathy and will take place over the next two years. This summer, I hired a postdoc who also has a doctorate in physical therapy for this trial as we work closely with the Department of Rehabilitation Medicine in the Clinical Center for this trial. I am also an Associate Investigator on an NINDS protocol entitled Clinical and Molecular Manifestations of Neuromuscular and Neurogenetic Disorders of Childhood. As part of this protocol, I took a 5-year project with me from NINDS when left NINDS and started with NINR. The project is a 5-year study of clinical outcome measures in two subtypes of congenital muscular dystrophy, Collagen VI-Related Myopathy and Laminin 2 Related Muscular Dystrophy. This past June 2014, I organized the 5th and final year of the study with my research team, a postbac fellow, a research nurse, and two summer students, including a nursing student and a doctor of pharmacy student. The study brought 35 patients to the Clinical Center over a week mid June in which the patients under went testing including motor function scales and timed tests, muscle and brain MRI, muscle ultrasound, and quality of life questionnaires. I was in charge of the logistics, patient recruitment, and data storage and analysis of this large project involving approximately 30 clinicians and researchers from across the country. A first author manuscript summarizing the first two-year pilot study of this 5-year longitudinal was accepted last month in Neuromuscular Disorders. Other manuscripts published this past year include: Clinical, pathologic, and mutational spectrum of dystroglycanopathy caused by LARGE mutations (Meilleur et al., J Neuropath & Experim Neurol, 2014); Genetics of low spinal muscular atrophy carrier frequency in sub-Saharan Africa (Sangare et al., Ann of Neurol, 2014); English cross-cultural translation and validation of the NM-Score; a system for motor function classification in patients with neuromuscular diseases (Vuillerot, C., Meilleur, K. et al., Arch of Phys Med & Rehab, 2014); Mosaicism for dominant collagen VI mutations as a cause for intra-familial phenotypic variability Donkervoort et al., Hum Mut, 2014).