Myology research highlights

The mTOR inhibitor rapamycin ameliorates the clinical and biochemical phenotype of mouse, worm, and cellular models of mitochondrial disease, via an unclear mechanism. Here, the authors show that prolonged rapamycin treatment improved motor endurance, corrected morphological abnormalities of muscle, and increased cytochrome c oxidase (COX) activity of a muscle-specific Cox15 knockout mouse (Cox15 sm/sm ). … [Read more]

A form of idiopathic inflammatory myopathy associated with anti-signal recognition particle (SRP) or anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies (aAb)  has been individualised and is referred to as immune-mediated necrotising myopathy (IMNM). The level of aAb correlates with IMNM activity and disease may respond to immunosuppression, suggesting that they are pathogenic. This study, xhich also involved clinicians … [Read more]

Generation of superoxide by xanthine oxidase can be stimulated under ischemic and aberrant calcium homeostasis. Given that patients and mice with Duchenne muscular dystrophy (DMD) are affected by ischemia and excessive calcium influx, this study tested the hypothesis that xanthine oxidase activity is elevated and contributes to disease pathology. Xanthine oxidase activity was measured by … [Read more]

Centronuclear myopathies (CNM) are a group of severe muscle diseases for which no effective therapy is currently available. The authors of the present study have previously shown that reduction of the large GTPase DNM2 in a mouse model of the X-linked form, due to loss of myotubularin phosphatase MTM1, prevents the development of the skeletal … [Read more]

Risdiplam (RG7916, RO7034067) is an orally administered, centrally and peripherally distributed, survival of motor neuron 2 (SMN2) mRNA splicing modifier for the treatment of spinal muscular atrophy (SMA). The objectives of this entry-into-human study were to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of risdiplam, and the effect of the strong CYP3A inhibitor itraconazole … [Read more]

Duchenne muscular dystrophy (DMD) is the most common X-linked neuromuscular condition manifested by progressive skeletal muscle weakness, cardiopulmonary involvement and cognitive deficits. Neurodevelopmental symptoms and signs are under-appreciated in this population despite the recognition that cognition has a major impact on quality-of-life. Here, the authors systematically evaluated the prevalence of neurodevelopmental needs, stratified based on … [Read more]

Titin-related myopathies are heterogeneous clinical conditions associated with mutations in TTN. To define their histopathologic boundaries and try to overcome the difficulty in assessing the pathogenic role of TTN variants, the authors of the present study performed a thorough morphological skeletal muscle analysis including light and electron microscopy in 23 patients with different clinical phenotypes … [Read more]

McArdle disease is a metabolic myopathy mainly characterised by symptom onset during physical activities or isometric muscle contraction. Resistance (also termed strength) training is a type of physical exercise focusing on the use of resistance (e.g., lifting weights) to induce muscular contraction, which builds muscle mass and strength. Historically people with McArdle disease were advised … [Read more]

Inherited peripheral neuropathies (IPN) represent a large heterogenous group of hereditary diseases with more than 100 causative genes reported to date. In this context, targeted next-generation sequencing (NGS) offers the opportunity to screen all these genes with high efficiency in order to unravel the genetic basis of the disease. Here, the authors compared the diagnostic … [Read more]

The dystrophinopathies include Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X-linked dilated cardiomyopathy (XLDCM). In recent years, co-ordinated multidisciplinary management for these diseases has improved the quality of care, with early corticosteroid use prolonging independent ambulation, and the routine use of non-invasive ventilation significantly increasing survival. The next target to improve outcomes is … [Read more]