Myology research highlights
RSS feedDystrophin rescue by trans-splicing: a strategy for DMD genotypes not eligible for exon skipping approaches
RNA-based therapeutic approaches using splice-switching oligonucleotides have been successfully applied to rescue dystrophin in Duchenne muscular dystrophy (DMD) preclinical models and are currently being evaluated in DMD patients. Although the modular structure of dystrophin protein tolerates internal deletions, many mutations that affect non-dispensable domains of the protein require further strategies. Among these, trans-splicing technology is … [Read more]
Effect of combined treatment with micro-dystrophin and follistatin on muscle physiology in aged dystrophic mice
Pharmacologic strategies have provided modest improvement in the devastating muscle-wasting disease, Duchenne muscular dystrophy (DMD). Pre-clinical gene therapy studies have shown promise in the mdx mouse model; however studies conducted after disease onset fall short of fully correcting muscle strength or protecting against contraction-induced injury. Here, the authors examine the treatment effect on muscle physiology … [Read more]
In vitro correction of a pseudoexon-generating deep intronic mutation in LGMD2A
Limb-girdle muscular dystrophy type 2A (LGMD2A) is the most frequent autosomal recessive muscular dystrophy. It is caused by mutations in the calpain-3 (CAPN3) gene. The majority of the mutations described to date are located in the coding sequence of the gene. However, it is estimated that 25% of the mutations are present at exon-intron boundaries … [Read more]
‘Pathognomonic’ muscle imaging findings in DNAJB6 mutated LGMD1D
The authors of the present study have previously reported clinical, genetic and molecular pathomechanistic findings in DNAJB6 mutated LGMD1D. After publishing clinical findings of the original Finnish family, more Finnish, Italian and US families with the same disease were identified, ultimately confirmed by mutations in the same gene. Of the total number of 28 examined … [Read more]
Feasibility and safety of assisted bicycle training in DMD boys
Physical training might delay the functional deterioration caused by disuse in boys with Duchenne muscular dystrophy (DMD). The “No Use Is Disuse” study is the first explorative, randomized controlled trial in boys with DMD to examine whether assisted bicycle training is feasible, safe, and beneficial. Ambulatory and recently wheelchair-dependent boys with DMD were allocated to … [Read more]
PMO mediated therapies for muscular disorders
Phosphorodiamidate morpholino oligomer (PMO)-mediated exon skipping is among the more promising approaches to the treatment of several neuromuscular disorders including Duchenne muscular dystrophy. The main weakness of this approach arises from the low efficiency and sporadic nature of the delivery of charge-neutral PMO into muscle fibers, the mechanism of which is unknown. In this study, … [Read more]
Nerve ultrasonography to clarify morphological differences between patients with demyelinating Charcot-Marie-Tooth disease and chronic inflammatory demyelinating polyneuropathy
Demyelinating Charcot-Marie-Tooth disease (CMT) and chronic inflammatory demyelinating polyneuropathy (CIDP) are both demyelinating polyneuropathies. The differences in nerve enlargement degree and pattern at multiple evaluation sites/levels are not well known. In this study, the authors investigated the differences in nerve enlargement degree and the distribution pattern of nerve enlargement in patients with demyelinating CMT and … [Read more]
Long-term cardiac outcomes in Andersen-Tawil syndrome patients
Andersen-Tawil syndrome (ATS) is an uncommon form of channelopathy linked to mutations in the KCNJ2 gene. Currently, little is known about the long-term arrhythmic prognosis of this disease. In this study, the authors conducted a retrospective multicentre study in nine French hospitals. Patients were recruited only if they were KCNJ2 mutation carriers. Thirty-six patients (female … [Read more]
PLEKHG5 gene mutations cause recessive intermediate Charcot-Marie-Tooth disease
Mutations in the Pleckstrin homology domain-containing, family G member 5 (PLEKHG5) gene has been reported in a family harbouring an autosomal recessive lower motor neuron disease (LMND). However, the PLEKHG5 mutation has not been described to cause Charcot-Marie-Tooth disease (CMT). To identify the causative mutation in an autosomal recessive intermediate CMT (RI-CMT) family with childhood … [Read more]
The motor neuron response to SMN1 deficiency in spinal muscular atrophy
This prospective study aimed to measure and analyse for up to 42 months, motor unit number estimation (MUNE) values longitudinally in 62 children with spinal muscular atrophy (SMA) types 2 and 3. Longitudinal electrophysiological data were collected, including compound motor action potential (CMAP), single motor unit action potential (SMUP), and MUNE. Significant motor neuron loss … [Read more]
