Blog Archives
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]
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]
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]
Cost of illness for neuromuscular diseases in the U.S
A comprehensive study of the costs associated with amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy (DMD) and myotonic dystrophy (DM) in the U.S was conducted. The total impact on the U.S. economy, including direct medical costs, non-medical costs, and loss of income was determined. Medical costs were calculated using a commercial insurance database and Medicare … [Read more]
Long-term efficacy of enzyme replacement therapy in late-onset GSDII
Type II glycogenosis (GSDII) is a rare and often fatal neuromuscular disorder caused by acid alpha-glucosidase deficiency. Although alglucosidase alfa enzyme replacement therapy (ERT) significantly improves outcomes in subjects with the infantile form, its efficacy in patients with the late-onset one is not entirely clear. The long-term efficacy of ERT in late-onset GSDII complicated by … [Read more]
Autologous myoblast transplantation for oculopharyngeal muscular dystrophy: a Phase I/IIa clinical study
Oculopharyngeal muscular dystrophy (OPMD) is a late onset autosomal dominant genetic disease mainly characterized by ptosis and dysphagia. The authors conducted a Phase I/IIa clinical study (ClinicalTrials.gov NCT00773227) using autologous myoblast transplantation following myotomy in adult OPMD patients. This study included 12 patients with clinical diagnosis of OPMD, indication for cricopharyngeal myotomy, and confirmed genetic … [Read more]
Respiratory muscle decline in DMD
Duchenne muscular dystrophy (DMD) causes progressive respiratory muscle weakness. The aim of this retrospective study was to analyse the trend of a large number of respiratory parameters to gain further information on the course of the disease. Forty-eight boys with DMD (age range 6-19 years old were followed in a multidisciplinary neuromuscular clinic between 2001 … [Read more]
Dystrophin 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]
