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There is a great demand for accurate non‐invasive measures to better define the natural history of disease progression or treatment outcome in Duchenne muscular dystrophy (DMD) and to facilitate the inclusion of a large range of participants in DMD clinical trials. This review aims to investigate which MRI sequences and analysis methods have been used and to identify future needs. Medline, Embase, Scopus, Web of Science, Inspec, and Compendex databases were searched up to 2 November 2019, using keywords “magnetic resonance imaging” and “Duchenne muscular dystrophy.” The review showed the trend of using T1w and T2w MRI images for semi‐qualitative inspection of structural alterations of DMD muscle using a diversity of grading scales, with increasing use of T2map, Dixon, and MR spectroscopy (MRS). High‐field (>3T) MRI dominated the studies with animal models. The quantitative MRI techniques have allowed a more precise estimation of local or generalized disease severity. Longitudinal studies assessing the effect of an intervention have also become more prominent, in both clinical and animal model subjects. Quality assessment of the included longitudinal studies was performed using the Newcastle‐Ottawa Quality Assessment Scale adapted to comprise bias in selection, comparability, exposure, and outcome. Additional large clinical trials are needed to consolidate research using MRI as a biomarker in DMD and to validate findings against established gold standards. This future work should use a multiparametric and quantitative MRI acquisition protocol, assess the repeatability of measurements, and correlate findings to histologic parameters.

Duchenne muscular dystrophy (DMD) and golden retriever muscular dystrophy (GRMD) are X-linked disorders caused by mutations in the DMD gene. Autophagy was recently identified as a secondary therapeutic target for DMD. We hypothesized that autophagy would be reduced in GRMD.Autophagic gene and protein expression was assessed in normal and GRMD skeletal muscles and correlated with phenotypic biomarkers.Muscles were differentially affected. Autophagy gene levels were lower than normal in the GRMD cranial sartorius (CS) but similar in the vastus lateralis (VL). Protein markers of autophagic flux, LC3B-II and p62, were higher in both GRMD muscles, in keeping with impaired autophagy. Protein levels correlated with a more severe phenotype. Autophagic structures were found in necrotic, fast-twitch GRMD myofibers.Our data suggest that autophagy is impaired in certain GRMD muscles. Differential GRMD CS involvement emphasizes that therapeutic modulation of autophagy could require specific muscle targeting. Muscle Nerve 58: 418-426, 2018.

Previous studies have tested the hypothesis that calpain and/or proteasome inhibition is beneficial in Duchenne muscular dystrophy, based largely on evidence that calpain and proteasome activities are enhanced in the mdx mouse.mRNA expression of ubiquitin-proteasome and calpain system components were determined using real-time polymerase chain reaction in skeletal muscle and heart in the golden retriever muscular dystrophy model. Similarly, calpain 1 and 2 and proteasome activities were determined using fluorometric activity assays.We found that less than half of the muscles tested had increases in proteasome activity, and only half had increased calpain activity. In addition, transcriptional regulation of the ubiquitin-proteasome system was most pronounced in the heart, where numerous components were significantly decreased.This study illustrates the diversity of expression and activities of the ubiquitin-proteasome and calpain systems, which may lead to unexpected consequences in response to pharmacological inhibition.

We tested the hypothesis that eccentric contractions (ECCs) rapidly induce greater-than-normal isometric torque drop in dystrophin-deficient golden retriever muscular dystrophy (GRMD) muscles. ECCs were imposed by forcibly stretching activated muscles. The results indicate that isometric torque drop was greater in GRMD versus controls (P < 0.0001). Our findings support the hypothesis that ECCs induce greater-than-normal isometric torque drop in GRMD muscles. The magnitude of ECC-induced isometric torque loss may be an ideal clinical endpoint in the GRMD model.

Glucocorticoid use may provide short-term functional improvement in boys with Duchenne muscular dystrophy (DMD). We report functional and histopathologic changes following a 4-month course of daily oral prednisone in a canine model of DMD, termed golden retriever muscular dystrophy (GRMD). Muscle extension forces in GRMD dogs treated daily with 1 and 2 mg/kg prednisone measured 2.349 +/- 0.92 and 3.486 +/- 0.67 N/kg, respectively, compared to 1.927 +/- 0.63 N/kg in untreated GRMD controls (p < 0.05 for 2 mg/kg group); GRMD muscle flexion forces measured 0.435 +/- 0.13 and 0.303 +/- 0.08 N/kg, respectively, compared to 0.527 +/- 0.01 N/kg in untreated GRMD controls (p < 0.05 for both groups). Although cranial sartorius hypertrophy and tibiotarsal joint angles also tended to improve, myofiber calcification increased and fetal myosin expression decreased following prednisone. Thus, functional data indicate benefit but histopathologic changes following prednisone treatment in GRMD suggest possible deleterious consequences.