OncoBone attended American Society for Bone and Mineral Research (ASBMR) Annual meeting 2021 virtually. The event was held in hybrid format including an in-person part in San Diego and an online- part open to all attendees. In the event, OncoBone presented a poster titled: “uKnee: a human osteoarthritic (OA) cartilage-on-chip model for efficacy screening of anti-OA drugs and medical devices” together with one of our CRO partners, BiomimX. This blog post summarizes the ASBMR event, provides references to selected exciting research in the OA field, and summarizes the poster we presented in the event.
ASBMR Annual meeting 2021
ASBMR Annual meeting 2021 was held in hybrid format including a possibility to attend virtually or in-person in San Diego, CA, USA. Most of the attendees were present virtually. The meeting comprised of four days of sessions including event Highlights, Meet the Professor and Cutting-Edge sessions, Oral and Poster presentations, and Networking either in-person or in chat- rooms provided for virtual participants.
Advances in OA research
OA is a prevalent musculoskeletal disease whose prevalence is expected to increase dramatically in the coming years due to population aging. Up to date, molecular mechanisms of OA initiation and progression are not well understood and there are no treatments available to restore degraded cartilage or decelerate disease progression. Luckily, there is a lot of research being conducted in this area both on the development of new therapies and establishing more predictive preclinical models that can enhance the therapy development, three examples of which are provided below.
Target identification by drug repurposing
One approach of finding new therapies can be through repurposing of existing drugs for OA that was presented in a poster presentation by researchers from the University of California. They used transcriptomics for comparing data from two mouse strains either sensitive or resistant to post-traumatic OA and used the data to identify therapeutic targets. Based on these targets, they identified over 60 FDA-approved therapies that could potentially be used for treating OA.
Advanced drug screening model based on organ-on-chip technology
OncoBone presented a poster in collaboration with BiomimX. The poster titled: “uKnee: a human osteoarthritic (OA) cartilage-on-chip model for efficacy screening of anti-OA drugs and medical devices” summarized the uKnee model that is developed and commercially offered by BiomimX. Dr. Paola Occhetta, CEO of BiomimX, describes the company and its business: “BiomimX is an Italian Startup, developer of Beating Organs-on-Chip solutions, able to integrate for the first time 3D mechanical environment characterizing human organs into miniaturized cell culture platforms. uKnee is one of our first models developed and validated in collaboration with worldwide recognized clinical experts in the field.”
Shortly, uKnee is a novel human mechanically active 3D osteoarthritic cartilage-on-chip model. The organ-on-chip technology can recapitulate the human pathology better than traditional cell culture models. What makes uKnee unique compared to other organ-on-chip models is the hyper-physiological mechanical stimulus provided by BiomimX’s proprietary uBeat® technology that mimics the natural movement activity of an adult. According to Dr. Occhetta, “the key advantage of the system is that uKnee enables for the first time to trigger clinically relevant traits of OA in vitro without the need of bombarding the system with supra-physiological doses of inflammatory cytokines. By only modulating 3D mechanical environment, we can mimic traumatic and chronic events happening in the joint during onset of the pathology.” The mechanical stimulus triggers OA-induced changes in primary human articular chondrocytes including enhancement of catabolic and inflammatory responses and switching towards hypertrophic cartilage phenotype characteristic of OA.
uKnee is an advanced tool for screening of novel disease-modifying OA drugs (DMOADs), and its performance has been demonstrated by testing clinically used SOCs and medical devices. The obtained results are consistent with data obtained from animal studies, highlighting the predictive power of the model. “According to our customers and collaborators, uKnee provides an unprecedented solution to study in-depth mechanisms underlying OA pathology and to detect highly specific effects of new leads. uKnee indeed represents a much more precise snapshot of healthy and osteoarthritic human cartilage as compared to currently available simplistic cell culture tools, finally providing high-content data that can be used to better design animal tests and clinical trials”, Dr. Occhetta comments on feedback received on uKnee.
To answer the growing need of new models, BiomimX is developing the uKnee model further. Dr. Occhetta comments on their ongoing R&D activities: “While uKnee currently integrates only the cartilage compartment, we are working towards integration of a full joint-on-chip encompassing also synovial membrane and subchondral bone. We are indeed aware that OA is a pathology of the joint as a whole, and we are working to provide our customers with this level of complexity”.
Close to human – animal models to confirm efficacy of experimental therapies
A research group from New York University of Grossman School of Medicine tested one FDA-approved therapy currently not indicated for OA in a mouse model and in a non-human primate model of OA. The therapy showed great potency by reducing articular cartilage destruction, osteophyte formation and OA pain, and by inducing thickening of subchondral bone. Use of multiple species improves the clinical predictivity of results, especially when results are confirmed in models resembling human diseases such as non-human primate models of OA.
Concluding remarks
ASBMR Annual meeting has always been a pleasure to attend. It brings together scientists in musculoskeletal research to share and discuss latest research. The restriction of the pandemic has hindered this and hopefully the situation allows traveling and attending the next Annual Meeting in person.
For additional information
If you have any questions related to the blog post or preclinical models described in the text, or you would like to receive a copy of the poster, please contact info@oncobone.com.
