Posted by Friends of FSH Research on Dec 1, 2020
Progress report by Charles Marusak
The aberrant expression of DUX4 is severely toxic to muscle tissues, resulting in oxidative stress and apoptosis of muscle cells degrading muscle function in FSHD Patients. As a transcription factor DUX4 is not easily targeted by traditional small molecule or biologic therapeutics. The focus of this project is to create an Antisense Oligonucleotide (ASO) therapeutic that can directly target and repress the DUX4 transcript. Our ASO is conjugated to an antibody that precisely delivers the therapeutic to muscle tissue.
In the first year of this work with the help of the Friends of FSH Research, miRecule has created a library of ASO-antibody conjugates for the treatment of FSHD. This library underwent extensive in vitro testing and four lead candidates were selected to undergo in vivo testing in mouse models of FSHD. This research will pave the way for our submission of our orphan drug application, and an eventual IND submission to the FDA so we may initiate phase I clinical trials. With the support of the highly collaborative FSHD community, we hope to create a therapeutic that can markedly improve the lives of patients suffering from this disease.
See original grant Antisense Oligonucleotide-Antibody Conjugates to Treat FSHD