G.P.28

• Published in: Neuromuscular disorders : NMD 2014-10, Vol.24 (9), p.802-803
• Main Authors: Margaron, Y.M, Fernandes, M, Morales, D, Degot, S
• Format: Article
• Language: English
• Subjects: Neurology
• ISSN: 0960-8966
• DOI: 10.1016/j.nmd.2014.06.042

Since classical ADME/Tox tests failed to detect statin drugs family as toxicant by inducing chronic muscle damages such as myositis, rhabdomyolysis, muscle pain; which leaded to a considerable economic burden for pharmaceutical industry, e.g. cerivastatin withdrawal from the market, companies need to develop more relevant in vitro models dedicated to muscle damage drug discovery. In this context, CYTOO developed a physiological muscle model improving the sensitivity of myotoxic drug detection. When cultured on 2D+ technology, primary human myoblasts faster differentiate in myotubes containing a higher level of sarcomere striation and nuclei alignment compared to standard culture condition. Moreover, 2D+ technology standardizes myotubes formation and enables accessing new parameters for myotubes characterization upon drug treatment. Thanks to the development of new image analysis algorithms and the reduced variability of myotubes morphology, we gain access to finer and more relevant readouts. To further demonstrate the benefits of our model, we tested reference drugs inducing hypertrophy or atrophy on both standard culture condition and 2D+ platforms. Our results showed that this model is robust and compatible with High Content Screening with increased Z ′ factors compared to standard assays. Altogether, the normalization of myoblast differentiation in highly mature myotubes, coupled to enhanced image analysis capacities, demonstrated a higher predictivity over standard assays and will allow the detection of myotoxic drugs during the early phases of preclinical studies for compound development.