Longitudinal Study of the Natural History of Duchenne Muscular Dystrophy (DMD)

Overview

The purpose of this study is to establish the largest long-term assessment of people with Duchenne muscular dystrophy (DMD). In this study, the investigators associated with the Cooperative International Neuromuscular Research Group CINRG) will take a detailed look (for a minimum of eight years) at DMD participant's physical abilities, the medical problems they experience, and how they use health care services. Physical abilities will be compared to a group of healthy controls. The second purpose of this study is to find out whether small, normal differences in the genetic makeup of people with DMD (called "single nucleotide polymorphisms" or "SNPs") affect how their disease progresses and relates to muscle strength/size and steroid response. The third purpose of this study is to study genetic variations associated with DMD. The final purpose of this study is to determine whether certain biomarkers are present in people with DMD and not in healthy controls.

Phenotyping Study 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, and relative risks of developing those conditions based on exposure to preventive interventions. 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 prednisone 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: Examine the associations between interventions and incidence and severity of secondary conditions, achievement of disease milestones and measures of motor function and mobility. Aim 8: To assess the validity and responsiveness of novel clinical outcome measures in DMD, including the 6-minute walk test (6MWT), the 9-hole peg test (9-HPT) Egen Klassification Scale(EK), the North Star Ambulatory Assessment (NSAA), and quantitative key and pinch grip strength testing. Aim 9: To assess the reliability, validity and responsiveness of novel patient-reported outcome(PRO) measures in DMD, including the NeuroQOL and PedsQL Neuromuscular Module. Aim 10: To assess the clinical meaningfulness of novel objective clinical outcome measures by assessing their ability to predict milestones of loss of ability to stand from supine, to stand from a seated position, to climb stairs, to ambulate independently and to raise a hand to the mouth. AIM 11: To determine the impact of development and growth on outcome measure performance,we will assess physical function on a group of healthy, typically developing male children and adults between 6 and 30 years of age for outcome measures of motor function and strength including the9-HPT, 6MWT, NSAA, timed function tests and quantitative muscle strength (QMT). Test results from this cohort will be used to develop initial percent predicted for age values for these assessments. SNP Genotyping Study Aim Our goal of the proposed study is to define polygenic modifiers of disease progression, and also response to treatment with glucocorticoids (prednisone and deflazacort). The most common type of human 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 are 90% of variation in the human genome. SNPs occur on the average of 1 per 1000 to 2000 bp throughout the 3.2 billion bp of the human genome while coding region SNPs (cSNPs) occur on the average of 1 per 346 bp. Genome-wide Association Study Aim Our goal of the proposed study is to isolate genomic DNA and find possible correlations of clinical phenotypes with gene loci associated with mild vs. severe clinical presentation, progression, or response to steroids. Serum Biomarkers Study Aim Our goal is to discover and validate sensitive and specific serum biomarkers for DMD.