A Pilot Study Examining Relationships between Magnetic Resonance Imaging, Alternative Splicing, and Functional Abilities in Myotonic Dystrophy Type 1


Translational Research

Poster Number: 125


S.H. Subramony, MD, University of Florida Health System, N C Olwe, BS, University of Florida, S L Riehl, BS, University of Florida, K S Nair, PT.PhD., University of Florida, E T Wang, Ph.D, University of Florida, Glenn Walter, PhD, University of Florida, Krista Vandenborne, PT, PhD, University of Florida, Donovan Lott, PT, PhD, CSCS, University of Florida

Introduction: The lack of sensitive, objective, and clinically relevant biomarkers is one of the largest obstacles in moving ahead with clinical trials for patients with Myotonic Dystrophy Type 1 (DM1). Both Quantitative Magnetic Resonance Imaging (qMRI) and alternative splicing have been explored as biomarkers to assess skeletal muscle and disease pathology in DM1. However, no studies have determined the correlation between these measures and their relationship to functional abilities in this patient population.

Objective: The purpose of this investigation was to examine the relationships between qMRI, alternative splicing, and functional abilities in people with DM1.

Methods: Nine ambulatory adults (six women, 37.8 + 13.4yrs) with DM1 participated. Fat fraction (FF) of the tibialis anterior (TA) muscle was quantified via qMRI. Biopsies from the TA muscle were processed for RNA extraction and RNA-Seq libraries. Percent Spliced In (PSI) values for all alternative exons were computed using MISO, and the 22 splicing events being developed as biomarkers for DM1 were specifically plotted. Quantitative muscle testing was done to determine the strength of the dorsiflexors. Mobility was assessed via the 10m fast walk test, Timed Up & Go, and the Six-minute walk test. Balance was also assessed by the Berg Balance Scale.

Results: FF correlated with balance measures, strength, and mobility (absolute r > 0.69). FF also correlated with seven of the 22 splicing events (absolute r > 0.70). Ten of the splicing events correlated with strength and mobility (absolute r > 0.70).

Conclusions: These preliminary data demonstrate novel information about these measures that should be of utility when considering optimal biomarkers in future clinical trials for DM1.