Blog Archives

PTC Therapeutics has started a safety and tolerability study in adult and pediatric patients with spinal muscular atrophy (SMA). The investigational compound developed by PTC in collaboration with corporate partner Roche and other entities, RG7800, is designed to increase levels of the SMN (survival of motor neuron) protein. A deficiency of full-length, fully functional SMN … [Read more]

Neuromuscular diseases (NMDs) are a group of over 200 highly genetically as well as clinically heterogeneous inherited genetic disorders that affect the peripheral nervous and muscular systems, resulting in gross motor disability. The clinical and genetic heterogeneities of NMDs make disease diagnosis complicated and expensive, often involving multiple tests. To expedite the molecular diagnosis of … [Read more]

In this study, the authors generated a novel monoclonal antibody, DAG-6F4, against alpha-dystroglycan which immunolabels the sarcolemma in human muscle biopsies. Its seven amino-acid epitope, PNQRPEL, was identified using phage-displayed peptides and is located immediately after the highly-glycosylated mucin domain of alpha-dystroglycan. On Western blots of recombinant alpha-dystroglycan, epitope accessibility was reduced, but not entirely … [Read more]

This study aimed to identify and characterize the molecular basis of a syndrome associated with myasthenia, cortical hyperexcitability, cerebellar ataxia, and intellectual disability. The authors performed in vitro microelectrode studies of neuromuscular transmission, performed exome and Sanger sequencing, and analyzed functional consequences of the identified mutation in expression studies. Neuromuscular transmission at patient endplates was … [Read more]

Antisense oligonucleotides (AONs) used to reframe dystrophin mRNA transcripts for Duchenne muscular dystrophy (DMD) patients are tested in clinical trials. Here, AONs are administered subcutaneously and intravenously, while the less invasive oral route would be preferred. Oral delivery of encapsulated AONs supplemented with a permeation enhancer, sodium caprate, has been successfully used to target tumor … [Read more]

Cardiac manifestations of Duchenne muscular dystrophy (DMD) include progressive cardiac dysfunction and an elevated resting heart rate (HR). Here, the authors hypothesized that this elevated HR reflects autonomic dysfunction that can be identified by heart rate variability (HRV) analyses, which will be associated with myocardial fibrosis by cardiac magnetic resonance imaging (cMR). DMD patients (N … [Read more]

Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset myopathy that progresses subacutely. If associated with a monoclonal gammopathy of unknown significance (MGUS), the outcome is unfavorable: the majority of these patients die within 1 to 5 years of respiratory failure. This study aims to qualitatively assess the long-term treatment effect of high-dose melphalan (HDM) … [Read more]

Myotonic dystrophy type 1 (DM1) is the most frequent muscular dystrophy in adult. The aim of this study was to investigate the natural history of skeletal muscle weakness in adults, in a cross-sectional, retrospective study. In a cohort of 204 adult DM1 patients, the authors quantified muscle impairment, handgrip force and physical disability. Muscle strength … [Read more]

Skeletal muscle disease resulting in weakness is common in late-onset Pompe disease (LOPD). Recent data implicate common bulbar muscle involvement (i.e., the tongue). The authors used quantitative assessment of lingual strength to determine retrospectively the frequency and severity of lingual weakness in LOPD. They additionally examined associations between lingual strength and the presence or absence … [Read more]