Blog Archives

Understanding the molecular pathways disrupted in motor neuron diseases is urgently needed. Here, the authors employed CRISPR knockout (KO) to investigate the functions of four ALS-causative RNA/DNA binding proteins (FUS, EWSR1, TAF15 and MATR3) within the RNAP II/U1 snRNP machinery. They found that each of these structurally related proteins has distinct roles with FUS KO … [Read more]

A majority of patients with immune-mediated necrotizing myopathy (IMNM)—a relatively new entity within the spectrum of idiopathic inflammatory myopathies (IIMs)—suffer from disability despite treatment, indicating inadequate management. Here, the authors conducted a cross-sectional study to investigate clinical and serologic characteristics in a case series of IMNM, including seronegative IMNM, diagnosed in tertiary referral hospitals in … [Read more]

Mitochondrial disorders, characterized by clinical symptoms and/or OXPHOS deficiencies, are caused by pathogenic variants in mitochondrial genes. However, pathogenic variants in some of these genes can lead to clinical manifestations which overlap with other neuromuscular diseases, which can be caused by pathogenic variants in non-mitochondrial genes as well. Mitochondrial pathogenic variants can be found in … [Read more]

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]