Anti-MYH2 monoclonal antibody

Various rodent models of statin-associated muscle symptoms (SAMS) have been used to investigate the aetiology of statin myotoxicity. Variability between these models, however, may be contributing to the ambiguity currently surrounding the pathogenesis of SAMS. Furthermore, few studies have assessed the reproducibility of these models. The aim of this study was to compare two established rodent models of statin myotoxicity, differing in treatment duration and dose, to determine which reproducibly caused changes characteristic of SAMS. Isolated skeletal muscle organ bath experiments, biochemical analyses, real-time quantitative-PCR and biometric assessments were used to compare changes in skeletal muscle and renal integrity in statin-treated animals and time-matched control groups. The SIM80 model (80 mg kg(-1 )day(-1) simvastatin for 14 days) produced fibre-selective skeletal muscle damage characteristic of SAMS. Indeed, fast-twitch gastrocnemius muscles showed increased Atrogin-1 expression, reduced peak force of contraction and decreased Myh2 expression while slow-twitch soleus muscles were unaffected. Contrastingly, the SIM50 model (50 mg kg(-1) day(-1) simvastatin for 30 days) produced little evidence of significant skeletal muscle damage. Neither statin treatment protocol caused significant pathological changes to the kidney. The results of this study indicate that the SIM80 model induces a type of SAMS in rodents that resembles the presentation of statin-induced myalgia in humans. The findings support that the SIM80 model is reproducible and can thus be reliably used as a platform to assess the aetiology and treatment of this condition.

Background Hereditary myosin myopathies are a group of rare muscle disorders, caused by mutations in genes encoding for skeletal myosin heavy chains (MyHCs). MyHCIIa is encoded byMYH2and is expressed in fast type 2A and 2B muscle fibers.MYH2mutations are responsible for an autosomal dominant (AD) progressive myopathy, characterized by the presence of rimmed vacuoles and by a reduction in the number and size of type 2A fibers, and a recessive early onset myopathy characterized by complete loss of type 2A fibers. Recently, a patient with a homozygous mutation but presenting a dominant phenotype has been reported. Methods The patient was examined thoroughly and two muscle biopsies were performed through the years. NGS followed by confirmation in Sanger sequencing was used to identify the genetic cause. Results We describe the second case presenting with late-onset ophthalmoparesis, ptosis, diffuse muscle weakness, and histopathological features typical for AD forms but with a recessiveMYH2genotype. Conclusion This report contributes to expand the clinical and genetic spectrum ofMYH2myopathies and to increase the awareness of these very rare diseases.