Investigator: Charles Marusak PhD
Category: Research - Translational
Muscle atrophy in FSHD is caused by aberrant expression of DUX4, a protein normally expressed in early development that is highly toxic to muscle cells. Currently, there are no FDA approved treatments for FSHD. Since DUX4 is a transcription factor it is not easily targeted by small molecule or protein therapeutics, which has hampered therapeutic development in the field. There is hope however, as RNA therapeutics have finally come of age with FDA approvals for similar disorders such as Duchene muscular dystrophy. Several research studies have shown that RNA therapeutics can directly repress DUX4 expression in muscle tissue and alleviating the pathology of FSHD in animal models. The main barriers for development of these therapeutics are improving the half-life of RNA therapeutics, and effective means of selective of delivery to muscle tissue. miRecule’s technology platform has the potential to address and overcome both barriers, allowing us to create an effective treatment for FSHD.
miRecule Inc. has developed revolutionary and patented chemistry to make highly stable RNA therapeutics. To enable delivery, we have also developed a modified antibody technology that can be conjugated to our RNA therapeutics and deliver them to targeted tissues. Conjugation to the antibody greatly improves the half-life of RNA therapeutics in circulation and improves distribution in dense tissues such a muscle. In this proposal we will develop an effective and safe RNA therapeutic targeting DUX4 conjugated to our muscle targeted antibody (miRecule canidate-DX4 or MC-DX4) as a treatment of FSHD. With the help of our collaborators we will test MCDX4 in preclinical animal models to prove it can eliminate DUX4 expression and halt disease progression. This research will pave the way for our submission of our orphan drug application, and eventual IND submission to the FDA so we may initiate phase I clinical trials. With the support of the friends of FSH as well as the highly collaborative FSHD community, we hope to create a therapeutic that can markedly improve the lives of patients suffering from this disease.