Myology research highlights

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Investigational RNAi therapeutic targeting C5 is efficacious in pre-clinical models of Myasthenia gravis

Complement-mediated damage to the neuromuscular junction (NMJ) is a key mechanism of pathology in myasthenia gravis (MG), and therapeutics inhibiting complement have shown evidence of efficacy in the treatment of MG. In this study, researchers describe the development of a subcutaneously administered N-acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) targeting the C5 component of complement that … [Read more]

CRISPR-Cas9 : first in vivo proof-of-concept in DM1

Teams of Ana Buj Bello (Genethon), Denis Furling (Institute of Myology) and Geneviève Gourdon (Imagine Institute) have made the proof-of-concept of a CRISPR-Cas9 approach in a mouse model of Steinert’s myotonic dystrophy, the most common neuromuscular disease in adults. Indeed, thanks to this genome editing approach, the expanded CTG triplet repeat in the DMPK gene, … [Read more]

Alteration of performance in a mouse model of Emery-Dreifuss muscular dystrophy caused by A-type lamins gene mutation

Autosomal Emery-Dreifuss muscular dystrophy (EDMD) is caused by mutations in the lamin A/C gene (LMNA) encoding A-type nuclear lamins, intermediate filament proteins of the nuclear envelope. Classically, the disease manifests as scapulo-humero-peroneal muscle wasting and weakness, early joint contractures and dilated cardiomyopathy with conduction blocks; however, variable skeletal muscle involvement can be present. Previously, researchers … [Read more]

Natural history of LGMD type R9 over 6 years: searching for trial endpoints

Limb girdle muscular dystrophy type R9 (LGMD R9) is an autosomal recessive muscle disease for which there is currently no causative treatment. The development of putative therapies requires sensitive outcome measures for clinical trials in this slowly progressing condition. This study extends functional assessments and MRI muscle fat fraction measurements in an LGMD R9 cohort … [Read more]

Biomarkers in inflammatory myopathies – an expanded definition

Biomarkers as parameters of pathophysiological conditions can be of outmost relevance for inflammatory myopathies. They are particularly warranted to inform about diagnostic, prognostic, and therapeutic questions. As biomarkers become more and more relevant in daily routine, this review focusses on relevant aspects particularly addressing myopathological features. However, the level of evidence to use them in … [Read more]

Open-label phase 2 clinical trial of ManNAc for GNE myopathy

The objective of this study was to assess long-term safety, tolerability, pharmacokinetics, and biochemical effect of ManNAc in subjects with GNE myopathy and identify clinical endpoints suitable for subsequent clinical trials. GNE myopathy is a rare, autosomal recessive myopathy caused by mutations in GNE, the gene encoding the rate-limiting enzyme in sialic acid biosynthesis. The … [Read more]

A phase 3 randomized study evaluating sialic acid extended-release for GNE myopathy

This study aimed to investigate the efficacy and safety of aceneuramic acid extended-release (Ace-ER), a treatment intended to replace deficient sialic acid, in patients with GNE myopathy. UX001-CL301 was a phase 3, double-blind, placebo-controlled, randomized, international study evaluating the efficacy and safety of Ace-ER in patients with GNE myopathy. Participants who could walk ≥200 meters … [Read more]

Inhibition of myostatin improves muscle atrophy in OPMD

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscle disease affecting one per 80 000 of the general population characterized by profound dysphagia and ptosis, and limb weakness at later stages. Affected muscles are characterized by increased fibrosis and atrophy. Myostatin is a negative regulator of muscle mass, and inhibition of myostatin has been demonstrated to … [Read more]

Newborn screening for SMA in Southern Belgium

Approval was recently granted for a new treatment for spinal muscular atrophy (SMA). Given that the treatment is effective when administered early and the societal burden of SMA-related disability, the implementation of a newborn screening program is warranted. The authors describe the stepwise process that led them to launch a newborn screening program for SMA … [Read more]

LRSAM1 variants and founder effect in French families with ataxic form of CMT2

Currently only 25-30% of patients with axonal forms of Charcot-Marie-Tooth disease (CMT) receive a genetic diagnosis. A team of clinicians aimed to identify the causative gene of CMT type 2 in 8 non-related French families with a distinct clinical phenotype. They collected clinical, electrophysiological, and laboratory findings and performed genetic analyses in four different French … [Read more]