Myology research highlights

  The publication of standardised care guidelines in 2010 was an important step towards improving DMD patient care. These guidelines were reproduced as “family guides”, and distributed to patients and health care providers via patient organisations, the TREAT-NMD network, and patient registries. The authors aimed to survey the extent to which these guidelines have been … [Read more]

  Duchenne muscular dystrophy is caused by dystrophin gene mutations which lead to the absence of the protein dystrophin. A significant proportion of patients suffer from learning and behavioural disabilities, in addition to muscle weakness. The authors of the present study have previously shown that these patients have a smaller total brain and grey matter … [Read more]

  Spinal muscular atrophy (SMA) is caused by homozygous inactivation of the SMN1 gene. The SMN2 copy number modulates the severity of SMA. The 0SMN1/1SMN2 genotype, the most severe genotype compatible with life, is expected to be associated with the most severe form of the disease, called type 0 SMA, defined by prenatal onset. This … [Read more]

  Nusinersen is a 2′-O-methoxyethyl phosphorothioate-modified antisense drug being developed to treat spinal muscular atrophy. Nusinersen is specifically designed to alter splicing of SMN2 pre-mRNA and thus increase the amount of functional survival motor neuron (SMN) protein that is deficient in patients with spinal muscular atrophy. This open-label, phase 2, escalating dose clinical study assessed … [Read more]

STIM1 is a reticular Ca2+ sensor composed of a luminal and a cytosolic domain. Missense mutations in the luminal domain have been associated with tubular aggregate myopathy (TAM), while cytosolic mutations can cause Stormorken syndrome, a multisystemic disease associating TAM with asplenia, thrombocytopenia, miosis, ichthyosis, short stature and dyslexia. Here, the authors present the case … [Read more]

Antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) have recently been associated with immune-mediated necrotizing myopathy, especially in patients with statin exposure. As the data are very limited concerning phenotypes and treatment in paediatric patients, this study aimed to identify the paediatric patients positive for anti-HMGCR antibodies and clarify their features and therapeutic strategies. Of 62 screend … [Read more]

  Mutations in HSPB1 are one of the commonest causes of distal Hereditary Motor Neuropathy (dHMN). Transgenic mouse models of the disease have identified HDAC6 inhibitors as promising treatments for the condition paving the way for human trials. A detailed phenotype and natural history study of HSPB1 neuropathy is therefore required in order to inform … [Read more]

  Congenital myopathies define a heterogeneous group of neuromuscular diseases with neonatal or childhood hypotonia and muscle weakness. The genetic cause is still unknown in many patients, precluding genetic counselling and better understanding of the physiopathology. To identify novel genetic causes of congenital myopathies, exome sequencing was performed in three consanguineous families. Two homozygous frameshift … [Read more]

  Immunogenicity of recombinant human acid-alpha glucosidase (rhGAA) in enzyme replacement therapy (ERT) is a safety and efficacy concern in the management of late-onset Pompe disease (LOPD). However, long-term effects of ERT on humoral and cellular responses to rhGAA are still poorly understood. To better understand the impact of immunogenicity of rhGAA on the efficacy … [Read more]

  Facioscapulohumeral muscular dystrophy (FSHD) involves sporadic expression of DUX4, which inhibits myogenesis and is pro-apoptotic. To identify target genes, the authors over-expressed DUX4 in myoblasts and found that the receptor tyrosine kinase (RTK) Ret was significantly up-regulated, suggesting a role in FSHD. They demonstrate that Ret is a novel mediator of satellite cell function, … [Read more]