“The most interesting thing about my research is seeing how a single protein, being produced where it should not, has such drastic effects on muscle function.”
Use of DNA-like molecules as a molecular Band-Aid to treat facioscapulohumeral muscular dystrophy
Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disorder that causes abnormal production of a toxic protein, the double homeobox protein 4 (DUX4), in muscles. 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, which are small pieces of DNA or RNA that can bind to specific molecules of RNA and block the ability of the RNA to make a protein or work in other ways. 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 an animal model of FSHD. The oligonucleotides with or without nanoparticles and saline will be tested to examine their effects.
The effectiveness of the treatment will be evaluated by testing the muscle strength and coordination of the model to see if there is any improvement. The pathology, levels of DUX4 gene transcripts and uptake of the oligonucleotides in muscle tissues will also be studied. This will show whether the lipid nanoparticles improve drug delivery into the tissue of our 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 the disorder that would otherwise leave patients with life-long disabilities.