Prolonged ambulation in Duchenne muscular dystrophy: An MRI study

Topic:

Translational Research

Poster Number: P154

Author(s):

Rebecca J Willcocks, PhD, University of Florida, Alison M Barnard, DPT, PhD, University of Florida, William D Rooney, PhD, Oregon Health and Science University, Sean C Forbes, PhD, University of Florida, Erika L Finanger, MD, MS, Oregon Health and Science University, Donovan J Lott, PT, PhD, University of Florida, Glenn A Walter, PhD, University of Florida, Krista Vandenborne, PhD, University of Florida

Dystrophinopathy in males is generally divided into Duchenne (DMD) and Becker muscular dystrophy (BMD). DMD is associated with out-of-frame genetic variants, absent dystrophin protein, and severe disease course, while BMD is associated with in-frame variants, partial dystrophin expression, and milder disease course. Phenotypically, ambulation past age 15 was traditionally considered BMD, while loss of ambulation prior to age 13 was considered DMD. However, care improvements have resulted in prolonged ambulation in many people with DMD. The aim of this study was to characterize genotype, clinical care, and muscle fat fraction trajectory measured by magnetic resonance spectroscopy (MRS) in individuals diagnosed with DMD who remained ambulatory at or beyond 16 years old. Data were from the ImagingNMD study, a longitudinal multicenter natural history study that included MRS and medical history including age at loss of ambulation. Among corticosteroid-treated participants (n=200), median age at loss of ambulation, estimated with Kaplan-Meier analysis with ambulatory individuals censored at oldest known ambulatory age, was 14.4 years. Among participants whose ambulatory status at age 16 was known (n=112), 18% remained ambulatory at 16 (n=20). Five participants were clinically rediagnosed with BMD (n=2) or had variants that may result in either DMD or BMD (n=3), maintained ambulation until at least 20 years, and had slower muscle fat fraction trajectories than the overall cohort. None used dystrophin restoration therapies. Fifteen participants had variants associated with DMD. 10 were treated with investigational or commercial dystrophin restoration therapies prior to age 16. Three untreated and 5 treated participants lost ambulation before age 18. Soleus and vastus lateralis fat fraction trajectories were heterogeneous, with some individuals having slow fat accumulation and others closely tracking the overall cohort. The natural history of individuals initially diagnosed with DMD includes a subset of people who maintain ambulation into their late teens or beyond.