Myology research highlights

The investigational oral drug ataluren, in development to treat Duchenne muscular dystrophy (DMD) resulting from a specific type of genetic mutation, has received conditional approval in the European Union (EU). This designation allows patients to gain access to an experimental drug before it is fully approved. Ataluren, originally known as PTC124 and now bearing the … [Read more]

Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough of premature stop codons in nonsense mutation (nm) genetic disorders. In this randomized, double-blind, placebo-controlled study males ≥5 years with nm-dystrophinopathy received study drug orally 3 times daily, ataluren 10, 10, 20 … [Read more]

Duchenne and Becker muscular dystrophy (DBMD) are allelic disorders caused by mutations in dystrophin. Patients with DBMB lack neuronal nitric oxide synthase (nNOS), which mediates physiological sympatholysis, thus ensuring adequate blood supply to working muscle. In mice lacking dystrophin, restoration of nNOS effects by a phosphodiesterase 5 (PDE5) inhibitor (sildenafil), improves skeletal and cardiac muscle … [Read more]

No treatment is available for patients affected by the recessively inherited, progressive muscular dystrophies caused by a deficiency in the muscle membrane repair protein dysferlin. A marked reduction in dysferlin in patients harboring missense mutations in at least one of the two pathogenic DYSF alleles encoding dysferlin implies that dysferlin is degraded by the cell’s … [Read more]

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle weakness caused by DMD gene mutations leading to absence of the full-length dystrophin protein in muscle. Multiple dystrophin isoforms are expressed in brain, but little is known about their function. DMD is associated with specific learning and behavioral disabilities that are more prominent in patients with … [Read more]

Most mutations that truncate the reading frame of the DMD gene cause loss of dystrophin expression and lead to Duchenne muscular dystrophy. However, amelioration of disease severity has been shown to result from alternative translation initiation beginning in DMD exon 6 that leads to expression of a highly functional N-truncated dystrophin. Here, the authors demonstrate … [Read more]

Multidisciplinary management of Duchenne Muscular Dystrophy (DMD) has achieved outstanding results in developed nations. This study aimed to describe the status of diagnosis and management of DMD in a developing country through the experience of non-profit organizations. A multistate, multiple-source, population-based survey was performed from medical records of 432 patients. Data were retrospectively collected, reviewed … [Read more]

Isis Pharmaceuticals has initiated a pivotal Phase III study evaluating ISIS-SMNRx in infants with spinal muscular atrophy (SMA), the most common genetic cause of infant mortality. The Phase III study entitled ENDEAR, is the first of several planned studies in a broad and comprehensive late-stage clinical development program for ISIS-SMNRx.  ENDEAR is a randomized, double-blind, … [Read more]

Mutations in fukutin-related protein (FKRP) gene cause a wide spectrum of disease phenotypes including the common limb-girdle muscular dystrophy 2I (LGMD2I), the severe Walker-Warburg syndrome, and muscle-eye-brain disease. FKRP deficiency results in α-dystroglycan (α-DG) hypoglycosylation in the muscle and heart, which is a biochemical hallmark of dystroglycanopathies. To study gene replacement therapy, the authors generated … [Read more]

There are no validated criteria for the diagnosis of sensory neuronopathy (SNN) yet. In a preliminary monocenter study, a set of criteria relying on clinical and electrophysiological data showed good sensitivity and specificity for a diagnosis of probable SNN. The aim of this study was to test these criteria in a French multicenter study. A … [Read more]