Myology research highlights

Duchenne muscular dystrophy (DMD) is a progressive, lethal neuromuscular disorder caused by the absence of dystrophin protein due to mutations of the dystrophin gene. Drisapersen is a 2′-O-methyl-phosphorothioate oligonucleotide designed to skip exon 51 in dystrophin pre-mRNA to restore the reading frame of the mRNA. This study assessed safety, tolerability, and pharmacokinetics of drisapersen after … [Read more]

Approximately 13% of boys with Duchenne muscular dystrophy (DMD) have a nonsense mutation in the dystrophin gene, resulting in a premature stop codon in the corresponding mRNA and failure to generate a functional protein. Ataluren (PTC124) enables ribosomal readthrough of premature stop codons, leading to production of full-length, functional proteins. This Phase 2a open-label, sequential … [Read more]

Most pathogenic mutations in Duchenne and Becker muscular dystrophies involve deletion of single or multiple exons from the dystrophin gene, so exon-specific monoclonal antibodies (mAbs) can be used to distinguish normal and mutant dystrophin proteins. In Duchenne therapy trials, mAbs can be used to identify or rule out dystrophin-positive “revertant” fibres, which have an internally-deleted … [Read more]

In Duchenne muscular dystrophy (DMD) and the mdx mouse model, the absence of the cytoskeletal protein dystrophin causes defective anchoring of myofibres to the basal lamina. The resultant myofibre degeneration and necrosis lead to a progressive loss of muscle mass, increased fibrosis and ultimately fatal weakness. Connective tissue growth factor (CTGF/CCN-2) is critically involved in … [Read more]

Nemaline myopathy (NM) is a rare congenital muscle disorder primarily affecting skeletal muscles that results in neonatal death in severe cases as a result of associated respiratory insufficiency. NM is thought to be a disease of sarcomeric thin filaments as six of eight known genes whose mutation can cause NM encode components of that structure, … [Read more]

Orphanet has published List of Research Infrastructures useful to Rare Diseases in Europe. This useful list is arranged by country and provides an exhaustive list of facilities that are extremely vital for rare disease research. Orphanet performs a systematic survey of the literature to provide an estimate of the prevalence of rare diseases in Europe. … [Read more]

Horizon 2020 is the biggest EU Research and Innovation programme ever with nearly €80 billion of funding available over 7 years (2014 to 2020) – in addition to the private investment that this money will attract. It promises more breakthroughs, discoveries and world-firsts by taking great ideas from the lab to the market. By coupling … [Read more]

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]

Multinational pharmaceutical company Eli Lilly is conducting a phase 3 trial of the drug tadalafil (Cialis), which may help regulate blood flow to muscles, in approximately 300 boys with Duchenne muscular dystrophy (DMD) who are 7-14 years old, able to walk, have adequate cardiac function and meet other study criteria. The rationale for using tadalafil … [Read more]

Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease affecting lower motor neurons. SMA is caused by mutations in the Survival Motor Neuron 1 (SMN1) gene, which result in reduced levels of functional SMN protein. Biochemical studies have linked the ubiquitously expressed SMN protein to the assembly of pre-mRNA processing U snRNPs, raising the possibility … [Read more]