189PElectrical impedance myography as a tool for monitoring disease progression in mouse models of Duchenne muscular dystrophy: a longitudinal, multisite study

Abstract

Establishing reliable readouts to monitor disease status and response to therapy in preclinical studies is vital, especially for rare neuromuscular disorders such as Duchenne muscular dystrophy (DMD). Electrical impedance myography (EIM) is a non-invasive technique where a weak, high-frequency electrical current is applied to muscle surface and the resulting voltage patterns measured. Changes in EIM components (i.e., resistance, reactance, phase) reflect muscle status. In recent years, EIM has shown promise as a tool to longitudinally assess disease-induced changes and effects of therapies in DMD patients and animal models. However, preclinical findings have been limited to single-site studies and narrow age ranges. As part of the 'Of Mice and Measures' (OMAM) study, aimed at obtaining comparative data on DMD murine models’ natural history, we carried out a multicenter study to validate EIM as a translatable preclinical-to-clinical tool in dystrophic settings. Monthly in vivo EIM measurements were performed at two independent sites (UniBa and LUMC), on the gastrocnemius of male mdx mice on different genetic backgrounds (classic, mildly affected BL10-mdx mice and hyper-fibrotic, more severely affected D2-mdx mice, vs. strain-matched wild types), from 8 to 52 weeks of age. First EIM training and data analysis were conducted at BIDMC. EIM data sets were largely comparable across study sites, with longitudinal phase values at a selected frequency (105 kHz) being the most reliable and accurate. EIM outcomes were affected by mouse strain and age, with D2-mdx mice showing considerably lower values consistent with typical muscle atrophy. Interestingly, histopathology evaluated at 8, 12, 28, or 52 weeks of age correlated well with EIM phase values in either strain, with the D2-mdx model showing far stronger correlations to features of disease severity. Globally, our findings highlight the applicability of EIM as a robust outcome measure for preclinical studies in DMD.