Myology research highlights

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]

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]

Spinal muscular atrophy (SMA) is the second most common genetic cause of death in childhood. However, no effective treatment is available to halt disease progression. SMA is caused by mutations in the survival motor neuron 1 (SMN1) gene. The authors of the present study have previously reported that PTEN depletion leads to an increase in … [Read more]

Prenatal testing based on cell-free fetal DNA in maternal serum is now possible for specific monogenic conditions. Studies have shown that prospective parents and health professionals support the use of non-invasive testing. However, some ethical issues have been raised concerning informed consent and paternal rights. The objective of this study was to explore ethical aspects … [Read more]

Spinal and bulbar muscular atrophy (SBMA) or Kennedy’s disease is an X-linked CAG/polyglutamine expansion motoneuron disease, in which an elongated polyglutamine tract (polyQ) in the N-terminal androgen receptor (ARpolyQ) confers toxicity to this protein. Typical markers of SBMA disease are ARpolyQ intranuclear inclusions. These are generated after the ARpolyQ binds to its endogenous ligands, which … [Read more]

Isis Pharmaceuticals has opened a second phase 3 trial to test its antisense drug, ISIS-SMNRx, in children with spinal muscular atrophy (SMA) who are 2 to 12 years old, not able to walk, and experienced their first disease symptoms after 6 months of age. ISIS-SMNRx is designed to alter the splicing of a closely related … [Read more]

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]

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]

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]

McArdle disease (Glycogen Storage Disease type V) is caused by an absence of muscle phosphorylase leading to exercise intolerance, myoglobinuria rhabdomyolysis and acute renal failure. This update of a review first published in 2004, systematically examined the evidence from randomised controlled trials (RCTs) of pharmacological or nutritional treatments for improving exercise performance and quality of … [Read more]