Myology research highlights

Exonic duplications account for 10%–15% of all mutations in Duchenne muscular dystrophy (DMD), a severe hereditary neuromuscular disorder. The authors report a CRISPR (clustered regularly interspaced short palindromic repeat)/Cas9-based strategy to correct the most frequent (exon 2) duplication in the DMD gene by targeted deletion, and tested the efficacy of such an approach in patient-derived myogenic … [Read more]

Immune mediated necrotising myopathies (IMNM) may be associated with anti-SRP or anti-HMGCR antibodies and the titre of these antibodies is correlated with the disease activity. In this study, the investigators have examined the hypothesis that anti-SRP and anti-HMGCR antibodies may be involved in muscle damage. Muscle biopsies of patients were analysed for atrophy and regeneration, … [Read more]

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant adult-onset disease characterized by progressive ptosis, dysphagia, and proximal limb weakness. The genetic cause is an expanded (GCN)n mutation in the PABPN1 gene encoding for the polyadenylate-binding protein nuclear 1. Here, the authors hypothesised a potential correlation between the size of the (GCN)n expansion and the severity … [Read more]

The SUNFISH trial, an international phase II study of the splice-modifying drug RO7034067 in people with type 2 or 3 spinal muscular atrophy (SMA), begins in France at I-Motion. The first French investigative centre of the SUNFISH trial has just opened: I-Motion is a paediatric clinical trial platform for neuromuscular diseases at the Institute of … [Read more]

This retrospective study evaluated the efficiency and tolerance of rituximab in the management of resistant myasthenia gravis (MG). Twenty-eight patients who received rituximab for the treatment of MG between 2004 and 2015 at Pitié-Salpétrière University Hospital (Paris, France) were included. The efficacy of rituximab was evaluated every 6 months by the myasthenic muscle score (MMS), … [Read more]

  This review presents recent findings of key biomolecular processes that underlie two motor neuron degenerative disorders, Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA). It focusses on the role of four multifunctional proteins involved in RNA metabolism (TDP-43, FUS, SMN and Senataxin) that play a causal role in these diseases and the reported … [Read more]

Not only is functional rehabilitation during inflammatory myopathies beneficial in terms of inflammation, but it also appears to result in functional improvement. Rehabilitation has long been discouraged in inflammatory myopathies for fear of aggravating muscle inflammation. In an article published in November 2016, members of the Department of Internal Medicine and Clinical Immunology at the … [Read more]

  In this study, clinical electrophysiology studies, exome and Sanger sequencing were used to identify the molecular basis and elucidate the pathogenesis of a fatal congenital myasthenic syndrome. Clinical electrophysiology studies of the patient revealed several-fold potentiation of the evoked muscle action potential by high frequency nerve stimulation pointing to a presynaptic defect. Exome sequencing … [Read more]

Myotonic dystrophy type 1 (DM1) is caused by (CTG⋅CAG)n-repeat expansion within the DMPK gene and thought to be mediated by a toxic RNA gain of function. Current attempts to develop therapy for this disease mainly aim at destroying or blocking abnormal properties of mutant DMPK (CUG)n RNA. Here, the authors explored a DNA-directed strategy and … [Read more]

  This study describes the phenotypic spectrum of distal hereditary motor neuropathy caused by mutations in the small heat shock proteins HSPB1 and HSPB8 and investigate the functional consequences of newly discovered variants. Among 510 unrelated patients with distal motor neuropathy, the authors identified mutations in HSPB1 (28 index patients/510; 5.5%) and HSPB8 (4 index … [Read more]