Accelerometric outcomes of motor function related to clinical evaluations and muscle involvement in dystrophic dogs.

Mutsuki Kuraoka,Yoshitsugu Aoki,En Kimura,Yuko Nitahara-Kasahara,Akihiko Shin,Hisateru Tachimori,Shin'Ichi Takeda,Naohiro Kato,Hiroyuki Shibasaki,Atsushi Asakura

doi:10.1371/journal.pone.0208415

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked muscle disorder characterized by primary muscle degeneration. Patients with DMD reveal progressive muscle weakness leading to ambulatory dysfunction. Novel outcome measures are needed for more sensitive evaluation of therapeutic effects in clinical trials. Multiple parameters of acceleration and angular velocity are used as efficient indicators to quantify the motion of subjects, and these parameters have been recently applied for evaluation of motor function in DMD. In the present study, we evaluated gait in a dystrophic dog model, CXMDJ, by measuring three-axial acceleration and angular velocity over the course of months. Hybrid sensors were placed on the dorsal thoracic and lumbar regions of dogs to detect a wide range of acceleration (±8 G) and angular velocity (±1000 degrees per second). Multiple parameters showed lower values in dystrophic dogs compared to wild-type (WT) dogs, and declined over the course of months. Acceleration magnitude (AM) at the thoracic region in dystrophic dogs was prominently lower compared with WT dogs, even at the age of 2 months, the onset of muscle weakness, whereas AM at the lumbar region drastically declined throughout the disease course. The angular velocity index in the vertical direction in the lumbar region increased in dystrophic dogs, suggesting waddling at the girdle. These parameters also accordingly decreased with exacerbation of clinical manifestations and a decrease in spontaneous locomotor activity. The AM of dystrophic dogs was analyzed with magnetic resonance imaging to look for a correlation with crus muscle involvement. Results showed that acceleration and angular velocity are multifaceted kinematic indices that can be applied to assess outcomes in clinical trials for hereditary neuromuscular disorders including DMD.

Highlights

Duchenne muscular dystrophy (DMD) is an X-linked disorder of muscle characterized by primary muscle degeneration [1]
We found that multiple parameters of acceleration and angular velocity declined according to disease severity and as the disease progressed, and that these parameters varied between the dorsal thoracic and lumbar regions
At the age of 2 months, which is the onset of muscle weakness in dystrophic dogs [32], Acceleration magnitude (AM) in dystrophic dogs were already lower compared with WT dogs, especially in the thoracic region

Summary

Introduction

Duchenne muscular dystrophy (DMD) is an X-linked disorder of muscle characterized by primary muscle degeneration [1]. A mutation in DMD results in the absence of dystrophin, a structural protein in muscle fibers, leading to fragility of muscle fibers following contractive force [2]. Histologic features of DMD are muscle fiber degeneration with secondary cellular inflammation, ineffective muscle fiber regeneration, and eventually fibrosis and adiposis. With the development of new therapies, sensitive outcome measures are needed to capture disease progression and monitor treatment effects. The 6-minute walking test, which measures the distance walked in 6 minutes, is a primary outcome measure of motor function in DMD [7, 8], but this test is not sufficiently sensitive to measure disease progression in younger boys [9]

Methods

Results

Discussion

Conclusion