Funding outcome

Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disorder that causes abnormal production of a toxic protein, the double homeobox protein 4 (DUX4), in muscle. It is one of the most common forms of muscular dystrophy affecting many children worldwide; however, there is no effective treatment for FSHD. Research into possible treatments involves finding methods to reduce DUX4 protein production. One possible method is using a molecular band-aid called antisense oligonucleotides as gene silencing molecules. Delivery into muscle cells can be enhanced through the use of lipid nanoparticles. In this project, I will test the effectiveness of antisense oligonucleotide treatment in a mouse model of FSHD. FSHD mice will be injected (with or without lipid nanoparticles or saline), and sacrificed 30 days later. Prior to sacrifice, various well-established functional tests will be performed to evaluate the improvement of muscle strength and coordination. Mice tissue samples will be collected and sectioned for histological analysis to assess muscle pathology. Additionally, DUX4 gene transcript levels will be measured via qRT-PCR. Finally, uptake of the antisense oligonucleotides into target tissues will be examined. This will show whether the lipid nano particles improve drug delivery into the tissue of our mouse model. I expect that this study will identify antisense oligonucleotide-mediated therapy that can be effectively used to treat FSHD as well as an efficient delivery system for it. The drug would be extremely impactful clinically as a treatment for a the disorder that would otherwise leave patients with life-long disabilities.