179PMethodology of the CINRG expanded Duchenne natural history study (eDNHS): assessing disease progression in the era of glucocorticoid and gene therapy treatments

Abstract

The Expanded Duchenne Natural History Study (eDNHS) is a multicenter prospective study aimed at evaluating the long-term progression of Duchenne muscular dystrophy (DMD). The study investigates how evolving clinical care, particularly the increasing use of glucocorticoid therapies and emerging gene repair and gene therapy interventions, influences disease progression in DMD patients. Building upon the original CINRG Duchenne Natural History Study (DNHS), initiated in 2005, the eDNHS includes planned enrollment of up to 500 male participants of any age diagnosed with DMD. Data collection incorporates comprehensive demographic and genetic profiling, physician assessments, and standardized functional evaluations. Key outcomes are measured using tools such as the North Star Ambulatory Assessment (NSAA), Performance of the Upper Limb Module (PUL), timed function tests, pulmonary function tests, and patient-reported outcomes related to function, behavior, and health satisfaction. The study also integrates biomarker discovery efforts. Longitudinal assessments are conducted at baseline, every 6 months through year 3, and annually thereafter for up to 10 years. The eDNHS captures the impact of glucocorticoids and gene therapies on disease progression, providing critical insights into treatment efficacy. It identifies functional milestones and biomarkers that are predictive of long-term outcomes. The study’s longitudinal design allows for the evaluation of the evolving clinical outlook for DMD patients. The eDNHS provides an up-to-date methodology for tracking disease progression in DMD, advancing evolving patient care standards and the development of new therapeutic agents. By incorporating both traditional treatments like glucocorticoids and novel gene therapies, the study supports regulatory approval processes and informs best practices for optimizing clinical care for individuals with DMD.