Duchenne muscular dystrophy (DMD) affects besides muscle also the brain, resulting in memory and behavioral problems. The consequences of dystrophinopathy on gross macroscopic alterations are unclear. To elucidate the effect of full-length dystrophin expression on brain morphology, we used high-resolution post-mortem MRI in mouse models that either express 0% (mdx), 100% (BL10) or a low amount of full-length dystrophin (mdx-XistΔhs). While absence or low amounts of full-length dystrophin did not significantly affect whole brain volume and skull morphology, we found differences in volume of individual brain structures. The results are in line with observations in humans, where whole brain volume was found to be reduced only in patients lacking both full-length dystrophin and the shorter isoform Dp140.

Duchenne muscular dystrophy is a severe muscle wasting disease, characterized by a severely reduced lifespan in which cardiomyopathy is one of the leading causes of death. Multiple therapies aiming at dystrophin restoration have been approved. It is anticipated that these therapies will maintain muscle function for longer and extend the ambulatory period, which in turn will increase the cardiac workload which could be detrimental for cardiac function. We investigated the effects of voluntary running exercise in combination with low dystrophin levels on function and pathology of skeletal muscle and heart. We divided 15.5-month old female mdx (no dystrophin), mdx-Xist Δhs (varying low dystrophin levels) and wild type mice (BL10-WT and Xist Δhs -WT) to either a sedentary or voluntary wheel running regime and assessed muscle function at 17.5 months of age. Thereafter, a cardiac MRI was obtained, and muscle and heart histopathology were assessed. We show that voluntary exercise is beneficial to skeletal muscle and heart function in dystrophic mice while not affecting muscle pathology. Low amounts of dystrophin further improve skeletal muscle and cardiac function. These findings suggest that voluntary exercise may be beneficial for skeletal muscle and heart in DMD patients, especially in conjunction with low amounts of dystrophin. key characteristic of cardiomyopathy is the dilated left ventricle, found in the majority of older DMD patients [3][4][5], while studies on right ventricular function are less coherent [6][7][8]. Early detection is challenging, since cardiac involvement does not always result into clinical symptoms due to exercise intolerance resulting from skeletal muscle weakness.Not only DMD patients, but also Becker muscular dystrophy (BMD) patients suffer from cardiac myopathy. BMD patients have in-frame mutations in the DMD gene leading to synthesis of reduced levels of truncated, but partially functional dystrophin proteins. Consequently, their muscle pathology is less severe than DMD patients. However, despite the expression of low dystrophin levels, about two thirds of BMD patients develop cardiomyopathy [9][10][11]. Similarly, DMD and BMD carriers, expressing 50% of dystrophin, also have an increased risk for cardiomyopathy [12,13].Currently there are two therapeutic strategies approved aimed to

No abstract

No abstract

No abstract