Posted by Friends of FSH Research on May 20, 2020
Progress report by Charles Marusak
RNA therapeutics have recently been demonstrated to be effective treatments for disorders similar to FSHD such as Duchene muscular dystrophy. Direct repression of DUX4 via antisense-oligonucleotides (ASOs), a type of RNA therapeutic, has been shown to alleviate the pathology of FSHD in animal models. Despite this potential, the serum half-life and muscle delivery of RNA therapeutics is very low and must be overcome. Here at miRecule, we are utilizing unique chemistry to improve ASO half-life and developing a modified antibody technology that can be conjugated to RNA, allowing for efficient muscle delivery.
In this project we have created a test library of ASO-antibody conjugates for FSHD. We are now screening this library in in vitro assays to select our lead candidates based on stability, non-specific side effects and efficacy. We have screened our library for stability in human serum and have identified properties that allow for greater conjugate half-life. We have initiated testing of our conjugates for non-specific side effects on PBMCs and DUX4 knockdown in differentiated myoblasts. Upon completion of our in vitro screens, we will select our lead candidates for in vivo mouse models. 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.
See original grant Antisense Oligonucleotide-Antibody Conjugates to Treat FSHD