Session Information
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose:
No therapy for osteoarthritis (OA) has yet to deliver both structural and symptomatic benefits. Symic is approaching this unmet clinical need with a novel matrix regulator, SB-061, inspired by aggrecan. Aggrecan is a critical component for cartilage structure and plays a key role as part of the protective molecules shielding collagen from degradation. Native aggrecan is lost early in the progression of OA and restoring the function of aggrecan in the joint is hypothesized to reduce OA progression. SB-061 was designed as a novel functional mimic of aggrecan, and was evaluated in a standard rodent model of OA.
Methods:
SB-061 was synthesized by linking the glycosoaminoglycan chondroitin sulfate (CS) with peptides known to bind to hyaluronic acid (HA). An ELISA assay was developed by immobilizing HA on a plate and using an antibody to the SB-061 molecule to confirm the concentration dependent binding of SB-061 to HA. In vivo experiments were performed to assess the pain reducing effect of SB-061. Rats received a medial meniscal tear in their right hind-limbs, and SB-061 was injected into the injured joint beginning 1 week after surgery and weekly throughout the study. Incapacitance testing was performed to detect differences in pain related responses (load bearing on the injured joint) throughout the duration of the 6-week study.
Results:
SB-061 demonstrates high affinity binding to HA (EC50 = 10nM) and produces a robust, dose related reduction in pain responses following intra-articular injection in a rat model of OA. The timecourse and magnitude of SB-061 mediated analgesic effects in the rat OA model were comparable across 4 independent studies with a maximum pain reduction of approximately 30% at week 4 of treatment. Continued weekly dosing of SB-061 resulted in a sustained reduction of pain throughout the course of the study, whereas termination of SB-061 dosing resulted in a diminishment of the pain relief effect over a two week period. These results are superior to historical data with a clinically relevant dose of an NSAID administered at similar times following the meniscal tear surgery. We hypothesize that SB-061 acts as a matrix regulator via its aggrecan-like properties to produce a sustained pain relieving effect in this model.
Conclusion:
We have demonstrated that SB-061 functionally mimics aggrecan with respect to binding to HA, and significantly reduces pain related responses in a sustained manner in an industry standard animal model of OA. These data suggest that SB-061 may exhibit clinical efficacy in human OA via a similar mechanism. Additional studies are underway to elucidate the mechanism of action of SB-061 within the joint and its potential for disease modification.
To cite this abstract in AMA style:
Stuart K, Chen J, Saha S, Kabra H, Chan A, Egodoge K, Oskins J, Lin C, Karsdal M, Chambers M, Paderi J. Sustained Efficacy of Intra-Articular SB-061, a Novel Matrix Regulator Inspired By Aggrecan, in a Rat Model of Osteoarthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/sustained-efficacy-of-intra-articular-sb-061-a-novel-matrix-regulator-inspired-by-aggrecan-in-a-rat-model-of-osteoarthritis/. Accessed .« Back to 2017 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/sustained-efficacy-of-intra-articular-sb-061-a-novel-matrix-regulator-inspired-by-aggrecan-in-a-rat-model-of-osteoarthritis/