A diagnostic and therapeutic secreted target protein that is upregulated in a subset of human patients with Osteoarthritis. It is a strong regulatory candidate for the transformation of maintenance chondrocytes into digestive aggravators of OA.

DESCRIPTION OF THE INVENTION:  The present invention relates to a diagnostic and therapeutic secreted target protein that is upregulated in a subset of human patients with osteoarthritis (OA).  The target also functionally correlates to OA in a rat model of the disease.  In vitro studies have confirmed that overexpression of this target: 1) decreases the expression of procartilage extracellular matrix proteins ie. aggrecan, type II collagen, and cartilage link protein, 2)  increases undesirable cell proliferation within the cartilage matrix, and 3) increases the production of digestive and inflammatory factors such as MMP-13, cathepsin, Adamts5, Cc12, and Tnfa.  The target is therefore a strong regulatory candidate for the transformation of maintenance chondrocytes into digestive aggravators of OA.

BACKGROUND:  OA is the most prevalent degenerative joint disease with 12% of adults being afflicted. The incidence of OA is expected to rise over the next decade with the aging population, which is predicted to drive the osteoarthritis market to US$7 billion by 2015. OA is characterized by articular cartilage degradation and is associated with chronic pain and disability.  In fact, OA is second only to chronic heart problems in being the cause of worksite disabilities.

Current therapies for OA including corticosteroids, NSAIDs, DMARDs, and opioids have been designed for symptom management in an attempt to improve patient mobility and quality of life.  These do not, however, affect the degradation of the cartilage and no current therapy is capable of inducing disease remission.  In addition, each of the current therapies has been linked to serious side effects, toxicity, and/or efficacy plateaus. Thus, there is an immediate need for drugs that are capable of modifying the disease, and stopping its progression at an early stage.

POTENTIAL ADVANTAGES/USES: 

• Can be an early diagnostic marker in combination with other markers (See Technology - Diagnostic System for Early Stage Osteoarthritis and Therapeutic Discovery)
• Can serve as basis for designing novel therapeutics aimed at modifying the disease state
• Target is a soluble secreted factor making it amenable for sequestering or inactivating
• Mechanism of action is via suppression of a well documented pro-cartilage transcription factor
• Inhibitors of target are readily and commercially available
• Candidate target for systemic or localized delivery

DEVELOPMENTAL STAGE: Preclinical proof of principle

Ref. #:  UWO-AH-002

 

Keywords:  Osteoarthritis, Cartilage degeneration, Bioinformatics, Diagnostic profile, Therapeutics, Chondrocyte, Growth factor, Extracellular matrix, Matrix metalloproteinase

 

Preclinical

US provisional application

Available for license and/or collaborative approach