Pharmacological Mobilization of Muscle Stem Cells to Treat Duchenne Muscular Dystrophy


Muscle Regeneration in Disease (includes satellite cells)

Poster Number: 113


Michael Rudnicki, OC, PhD, FRSC, Johnathan Smid, Sridhar Narayan, Michael Cross, Ricardo Carmona, Frank Gleeson


1. Ottawa Hospital Research Institute, 2. Ottawa Hospital Research Institute, 3. Satellos Bioscience Inc., 4. Satellos Bioscience Inc., 5. Ottaw Hospital Research Institute, 6. Satellos Bioscience Inc.

The Rudnicki lab discovered that absence of dystrophin leads to loss of polarity in satellite stem cells and reduced asymmetric division during regeneration. Notably, agonism of the EGFR-Auka pathway restores regenerative capacity in mdx mice through restoration of satellite cell polarity and asymmetric division. Satellos Bioscience (SBI) was formed to translate these research findings into a disease modifying therapeutic for DMD.

SBI is developing a drug that will restore regenerative function DMD satellite cells.

SBI has developed chemistry against a novel target in satellite cells PTP-x, that when inhibited promotes asymmetric division. SAR refinement of prioritized hits has resulted in the generation of a lead drug that demonstrates preclinical efficacy in mdx mice.

SBI has developed a series of lead candidates, that display selective and high affinity binding to the target PTP-x, stimulate asymmetric muscle stem cell divisions in myofiber assays and robustly activates P-EGFR in muscle following IV injection. To assess efficacy of drug treatment, we dosed 6-week old mdx mice by IP injection 3-times per week for 4 weeks. We observed a dramatic increase in distance travelled by treated mdx mice in free wheel running over this time. In situ force generation assessment indicated robust increases in maximum tetanic force of the tibialis anterior (TA) muscle of treated mdx mice, comparable to that of wild type. Notably, the body weight of treated mdx mice remained unchanged suggesting no overt toxicity of the treatment.

SBI has developed novel chemistry to inhibit a unique target in muscle, resulting in the restoration of regenerative asymmetric stem cell divisions in Duchenne Muscular Dystrophy. We aim to further optimize our preliminary leads to support the initiation of IND enabling studies in H1 2020, with the goal of entering the clinic in 2021.