UCD0305: LONGITUDINAL STUDY OF THE RELATIONSHIP BETWEEN IMPAIRMENT,

Children'S Research Institute, Washington DC

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this study is to establish a registry and a longitudinal database to describe the phenotypic variability (impairment, activity limitation, participation), and quality of life of persons with Duchenne muscular dystrophy (DMD). This multi-centered natural history study is investigator-initiated and is funded by the National Institute of Disability and Rehabilitation Research that is housed within the U.S. Department of Education. This is a 5-year prospective study that will collect the clinical data that is routinely acquired during clinical evaluation of persons with Duchenne muscular dystrophy. A second purpose of this study is to find out whether small normal differences in single nucleotide polymorphisms (SNPs) affect the disease progression and response to steroid treatment. This study is a multi-center trial that is initially being conducted at UC Davis and at the Center for Genetic Medicine, Children's Hospital in Washington D.C. Specific Aims. Aim 1: Longitudinally assess body function and body structure (impairment) through the measurement of anthropometrics, muscle strength and pulmonary function in subjects with DMD through the multicenter CINRG network. Aim 2: Longitudinally assess activity limitations in subjects with DMD through CINRG with timed motor performance, burden of care, and functional status. Aim 3: Longitudinally assess secondary conditions in subjects with DMD. Aim 4: Longitudinally assess participation, life satisfaction, service utilization and health-related quality of life in subjects with DMD. Aim 5: Determine appropriate outcome measurements for impairment, activities (activity limitations), participation and quality of life to determine the effect of glucocorticoids (prednisone, deflazacort) and other therapeutic interventions on these factors. Aim 6: Using the most robust impairment, activity, participation and quality of life outcome measures, determine the sample size, power and statistical methods for the analysis of the effect size for future planned randomized-controlled rehabilitation interventions in DMD. Aim 7: Define the polygenic modifiers of disease progression by examining the relationship between variations of single-nucleotide polymorphisms (SNPs), disease progression and response to glucocorticoid treatment. In addition to the abovementioned phenotype-related aims, we will seek to define polygenic modifiers of disease progression and response to treatment with glucocorticoids. The most common type of genetic variation is the single-nucleotide polymorphism (SNP), a base position at which two alternative bases occur at an appreciable frequency (1%) in the population. SNPs account for 90% of the variation in the human genome and have been identified as drug response and disease progression modifiers in a number of other disorders.