Genea Biocells scientists presented work from four disease modeling projects at the 2017 Muscular Dystrophy Association (MDA) Scientific Conference in Arlington, VA in March. The conference overall was an inspiring and fascinating exhibition of the world’s muscle disease research, with hundreds of attendees working to foster discussion and collaboration toward improving the lives of patients affected by a variety of muscular dystrophies.
Our data on pluripotent stem cell-derived skeletal muscle cells affected by Facioscapulohumeral Muscular Dystrophy (FSHD) identified three new classes of compounds, all with different molecular targets, that activate DUX4 expression during muscle development. These findings provide insights into the mechanism of DUX4-mediated toxicity and possible therapeutic targets. Dr. Charles Emerson, Jr. (University of Massachusetts) also shared his work on understanding FSHD muscle development by using pluripotent cells coaxed to become muscle using Genea Biocells differentiation media. His work will help our field to develop more effective therapies and a better understanding of FSHD myogenesis.
We also presented collaborative studies with Drs. Lingjun Rao and Nenad Bursac (Duke University) on 2-D and 3-D stem cell-derived in vitro models of Becker and Duchenne Muscular Dystrophies (B/DMD). These studies validated known disease markers in 2-D cell models and assessed force generation between control and disease-affected “myobundles” in 3-D. The ability to measure clinically relevant endpoints, such as muscle force, using a renewable human stem cell based platform should not only improve drug discovery throughput and assay reproducibility, but also greatly improve the translation from preclinical screens to clinical settings.
Lastly, our work on Myotonic Dystrophy (DM) and Emery-Dreifuss Muscular Dystrophy (EMD) identified disease-specific tissue culture phenotypes that serve as useful measures for cell-based assays and therapeutics testing. In Myotonic Dystrophy-affected pluripotent cell derived myoblasts and myotubes we described quantification of the disease’s characteristic MBNL foci, known to sequester splicing factors and cause pathogenic splicing effects in DM muscle. Additionally, in our EMD-affected myogenesis model harboring a LMNA mutation we could identify abnormal myonuclear eccentricity and ATP depletion phenotypes. These contributions lend valuable insights into the pathophysiology of DM and EMD and provide screenable phenotypes for therapeutics development assays.
Overall the 2017 MDA conference provided a great opportunity for our scientists to share their latest breakthroughs with the research community, learn and exchange ideas with distinguished researchers in the field, and foster new collaborations to help expedite the development of effective therapeutics for these devastating diseases. We found the meeting to be both educational and inspirational for our work.