REFERENCE NUMBER UWO-JL-075, UWO-JJ-012 and UWO-AC-015.

THERAPEUTIC AREAS Spinal Fusion, bone or cartilage regeneration, bone repair, musculoskeletal tissue engineering, osteoarthritis, ostoporosis and other skeletal disorders

DESCRIPTION OF THE INVENTION The IP-portfolio covers the use of retinoid acid receptor antagonists in cartilage formation (chondrogenesis) and bone formation (osteogenesis) for a variety of applications related to therapeutics, medical devices, and tissue engineering. The invention includes a validated highly effective screening system for potential RAR antagonists that would be of significant value to a pharmaceutical or biotechnology company with a focus on bone and tissue repair. This screening system was successfully applied to identifying a suite of proprietary RAR antagonists that promote bone healing in a rat critical sized defect model.

BACKGROUND Skeletal disease and trauma are a leading cause of debilitation and reduced quality of life, and represent a large socioeconomic burden on society. Many of these conditions involve loss of cartilage or bone. Vitamin A and its metabolites, the retinoids, play critical roles in the development and homeostasis of a number of tissues, including the skeleton. The retinoids, of which retinoid acid exhibits the greatest biological activity, function by interacting with retinoid acid receptors (RARs) to regulate gene expression. Researchers at UWO have used a variety of in vitro models to demonstrate that inhibition of RAR- mediated signaling, using RAR-selective antagonists, stimulates chondroblast and osteoblast differentiation, leading to cartilage and bone formation. Further, the inventors have developed a thorough understanding of the action of RAR antagonists on chrondrocyte and osteocyte differentiation and function. These studies have laid the groundwork for the clinical application of RAR antagonists in therapeutic areas relating to cartilage and bone formation and repair.

POTENTIAL ADVANTAGES/USES The present invention will be of interest to pharmaceutical and biotechnology companies developing peptide, nucleic acid or small molecule-based therapeutics for bone or cartilage regeneration, bone repair, musculoskeletal tissue engineering, osteoarthritis, osteoporosis and other skeletal disorders. The technology is available for license and provides access to in-depth expertise and to a as well as a comprehensive patent portfolio relating to the use of RAR antagonists for a variety of applications. This technology also presents a unique and validated tool to identify novel RAR antagonist drug molecules for use in treating musculoskeletal disorders.

Issued EP1131067 patent; other patents pending

The technology is available for licensing. Collaborative research proposals are an option