S160 Abstracts / Neuromuscular Disorders 29 (2019) S37–S208 P.318 MRI evaluation of skeletal muscle in the deltaE50-MD dog model of Duchenne muscular dystrophy N. Hornby , R. Drees, D. Wells, R. Piercy Royal Veterinary College, London, UK There is currently no cure for the fatal X-linked disorder Duchenne muscular dystrophy (DMD) and clinically-applicable translational trials continue to rely heavily on use of animal models. The Royal Veterinary College has a unique colony of dystrophin deficient dogs: the deltaE50-MD dog model. Magnetic Resonance Imaging (MRI) is a valuable non-invasive technique for monitoring the progression of the disease in human DMD patients. The aim was to determine if the deltaE50-MD dog has a skeletal muscle MRI phenotype that resembles that of DMD boys and to determine MRI differences of skeletal muscles in dystrophic and wildtype dogs. MRI was conducted in 15 deltaE50-MD dogs and 10 age-matched littermate wildtype male dogs under general anaesthetic, every 12 weeks from 3 months to 18 months of age. Up to 7 pelvic limb muscles and 4 lumbar muscles were assessed bilaterally in each dog. Four MRI biomarkers assessed were muscle volume normalised to femur length, T2 map signal intensity (SI), T1w to post gadolinium T1w SI ratio and muscle heterogeneity. The mean was calculated for each pair of muscles for all MRI biomarkers. Mixed model analyses (SPSS) were used to examine differences between groups at different ages. Muscle volumes were significantly smaller (p<0.001) in affected dogs when compared to wildtype dogs in all examined muscles, apart from the cranial sartorius. T2 map SI (p<0.001) and muscle heterogeneity (p<0.05) were significantly higher in affected dogs when compared to wildtype dogs. Affected dogs had significantly increased post gadolinium T1w SI in all muscles (p<0.05), apart from the cranial sartorius muscle, when compared to wildtype dogs. The most useful MRI biomarkers found in this study were muscle volume normalised to femur length and T2 map SI. Both of these biomarkers were able to show differences between groups and track changes longitudinally. These MRI biomarkers will be useful to determine efficacy of therapeutic clinical trials in the colony. http://dx.doi.org/10.1016/j.nmd.2019.06.432 P.319 Evaluation and reproducibility of a 6 minute walk test (6MWT) for non-invasive, phenotypic assessment of deltaE50-MD dogs, a model of Duchenne muscular dystrophy N. Hornby, D. Wells, R. Piercy, R. Harron Royal Veterinary College, London, UK Duchenne muscular dystrophy (DMD) is an X—linked disorder in which absence of dystrophin protein causes progressive skeletal / cardiac muscle degeneration and death within the third decade. Dystrophic dogs are commonly used in preclinical evaluation of treatments, because unlike rodents, they display functional deficits similar to those of affected humans. The distance walked in 6 minutes (6MWT) is a key performance biomarker of boys with DMD. We hypothesised (1) that a comparable 6MWT would discriminate affected deltaE50—MD dogs from littermate controls and (2) that results would be reproducible within individual animals over a 72 hour period. DMD dogs (n=up to 21) and littermate control dogs (n= up to 14) underwent a standard 6MWT every 3 months up to 18 months of age, starting at 3 months old, each on 2 occasions within 72 hours. The distance travelled of a 14m lap in 6 minutes was recorded. Absolute distance covered, and distance normalised to femur length (derived from MRI data) were compared between dogs of different genotypes at each age. Distances in the first of the 2 tests at each time point were correlated and compared with the second test result. DMD dogs walked significantly shorter absolute and height— adjusted distances in the 6MWT than their normal littermate controls as they aged (p<0.05). The distance walked by DMD dogs, tended to plateau beyond 6 months of age. There were no significant differences between first and second trials within each genotype for any age group. Further, there were highly significant, moderately strong correlations (P<0.0001; r2 ∼0.5) between the first and second trials in both WT and DMD dogs, suggesting fair test reproducibility. There were no significant differences detected between the first and second test results at any time point for either WT or DMD dogs. In conclusion, a 6MWT reliably discriminates affected deltaE50—MD dogs from controls and should prove useful amongst other testing for evaluation of treatment efficacy. http://dx.doi.org/10.1016/j.nmd.2019.06.433 P.320 Cardiac phenotypic expressions in female carriers of a canine model of Duchenne muscular dystrophy Y. Fromes 1 , I. Barthelemy 2 , X. Cauchois 2 , J. Boisserie 1 , J. Lelouer 1 , B. Marty 1 , S. Blot 2 , P. Carlier 1 1 Institute of Myology, Paris, France; 2 ENVA, Maisons-Alfort, France Golden Retriever muscular dystrophy (GRMD) represents an animal model that recapitulates human Duchenne muscular dystrophy (DMD) and provides a unique tool to investigate the pathogenic mechanisms and clues to understand the disease process. The primary presenting symptom in most dystrophinopathies is skeletal muscle weakness. However, cardiac muscle is similarly affected in DMD. Human female carriers of DMD, although frequently asymptomatic, can develop cardiac abnormalities. Our primary goal was to use female GRMD carriers as a test model for this subset of patients and establish a comprehensive reference dataset on a population of young adult GRMD carriers (N=19, 2 to 8 years) compared to healthy controls (N=8). Methodological approach was based on structural and functional evaluations, involving cardiac MRI as well as ECG Holter monitoring. Necropsy data should be correlated to the in vivo observations. In the context of cardiomyopathies, alterations of the cardiac rhythm as well as modifications of the cardiac interstitium like fibrosis, usually precede the appearance of overt systolic dysfunction. Preliminary results reveal quantifiable abnormalities in myocardial structure, contractile function or cardiac rhythm in all female carriers. Whereas, global ejection fractions were preserved, alterations of segmental contractility were observed. The longitudinal relaxation time constant (T1) of the myocardium was altered and might be due to increased water content or other changes of the local molecular environment related to fibrosis. All the carrier females presented with severe ventricular arrhythmias grading from 3a (polymorphism) to 4b (salvos) in the Lown classification. Some animals also presented with supraventricular arrhythmias. At necropsy, all female carriers had obvious myocardial fibrosis. Thus, female GRMD carriers appear as a valuable animal model to explore further the pathophysiology of the subset of female patients carrying a dystrophin mutation. http://dx.doi.org/10.1016/j.nmd.2019.06.434 P.321 Diaphragm echodensity and function in mdx mice by non-invasive ultrasonography: validation and correlation with in vivo and ex vivo functional readouts P. Mantuano 1 , A. Mele 1 , O. Cappellari 2 , A. Fonzino 1 , F. Sanarica 1 , A. De Luca 1 1 University of Bari, Bari, Italy; 2 University of Manchester, Manchester, UK In the mdx mouse model of Duchenne muscular dystrophy (DMD), diaphragm (DIA) alterations occur at early age, with a progression which closely resembles patients’ condition. High frequency ultrasound has been recently proposed as a longitudinal, non-invasive technique to monitor the progression of mdx DIA dysfunction. At present, data available are still limited, particularly in mdx mice at early disease stages. Moreover, no evidence has ever been provided about the usefulness of ultrasonography