Myology research highlights

Outcome measures for clinical trials in neuromuscular diseases are typically based on physical assessments, which are dependent on patient effort, combine the effort of different muscle groups, and may not be sensitive to progression over short trial periods in slow-progressing diseases. In this study, the authors hypothesised that quantitative fat imaging by MRI (Dixon technique) … [Read more]

Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, with a fairly homogeneous clinical phenotype (progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, and depressed tendon reflexes). With more than 40 genes implicated, an update of the present and rather confusing classification of CMT is needed. Over the last few years, … [Read more]

Charcot-Marie-Tooth 1A (CMT1A) is a demyelinating hereditary neuropathy whose pathogenetic mechanisms are still poorly defined and an etiologic treatment is not yet available. An abnormally high intracellular Ca2+ concentration ([Ca2+ ]i ) occurs in Schwann cells from CMT1A rats (CMT1A SC) and is caused by overexpression of the purinoceptor P2 × 7. Normalization of the Ca2+ levels … [Read more]

Congenital myopathies are heterogeneous inherited diseases of muscle characterized by a range of distinctive histologic abnormalities. Herein, the authors have studied a consanguineous family with congenital myopathy. Genome-wide linkage analysis and whole-exome sequencing identified a homozygous nonsense mutation in 3-hydroxyacyl-CoA dehydratase 1 (HACD1) in affected individuals. The mutation results in non-sense mediated decay of the … [Read more]

In prior open-label studies, eteplirsen, a phosphorodiamidate morpholino oligomer (PMO), enabled dystrophin production in Duchenne muscular dystrophy (DMD) with genetic mutations amenable to skipping exon 51. The present study used a double-blind placebo-controlled protocol to test eteplirsen’s ability to induce dystrophin production and improve distance walked on the 6-minute walk test (6MWT). DMD boys aged … [Read more]

An international Clinical Outcomes Group consisting of clinicians, scientists, patient advocacy groups, and industries identified a need for a scale to measure motor performance of the upper limb. This study reports the steps leading to the development of the Performance of the Upper Limb (PUL), a tool specifically designed for assessing upper limb function in … [Read more]

In this study, the authors aimed to develop RNA splicing biomarkers of disease severity and therapeutic response in myotonic dystrophy type 1 (DM1) and type 2 (DM2). In a discovery cohort, they used microarrays to perform global analysis of alternative splicing in DM1 and DM2. The newly identified splicing changes were combined with previous data … [Read more]

Myotonic dystrophy type 1 (DM1) is an inherited dominant muscular dystrophy caused by expanded CTG•CAG triplet repeats in the 3′ UTR of the DMPK1 gene, which produces a toxic gain-of-function CUG RNA. It has been shown that the severity of disease symptoms, age of onset and progression are related to the length of the triplet … [Read more]

Genetic defects in calpain3 (CAPN3) leads to Limb-Girdle Muscular Dystrophy type 2A (LGMD2A), a disease of the skeletal muscle that affects predominantly the proximal limb muscles. The authors of this study have previously demonstrated the potential of Adeno-Associated Virus (AAV)-mediated transfer of the CAPN3 gene to correct the pathological signs in a murine model for … [Read more]

In this retrospective study that took place over the last 30 years, the life expectancy in patients suffering from Duchenne muscular dystrophy (DMD) was investigated by analysing the role of ventilatory assistance and causes of death. One hundred and nineteen adult DMD patients were followed from 1981 to 2011 at the AFM Yolaine de Kepper … [Read more]