The present invention relates to osteoarthritis (OA) and methods of OA diagnosis and treatment via the findings of a genome-wide analysis of dysregulated genes in OA.

Keywords:  Osteoarthritis, cartilage degeneration, therapeutics, therapeutic kit, diagnostic marker

 

DESCRIPTION OF THE INVENTION:  The present invention relates to osteoarthritis (OA) and methods of OA diagnosis.   The invention covers methods by which one might diagnose OA through differential expression profiling of chondrocyte-specific genes or proteins. The targets were identified using a genome-wide analysis of dysregulated genes in a specialized rat OA model that best models the human progression of the disease. The technology can manifest itself as a kit to diagnose OA using at least one probe directed to a chondrocyte-specific gene that exhibits differential expression of at least 1.5-fold in contrast to standardized undiseased conditions.  Additional methods are covered in which downregulation or upregulation of certain genes and/or proteins may be monitored to determine the efficacy of various treatment regimes.  Similarly, this profile may be used in the determination of mechanism or effectiveness of compounds during in vitro screening. 

 

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 an aging and increasingly overweight industrialized 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. There are no guidelines or tests available for early diagnosis of OA and patients are diagnosed only once the disease has progressed to the point wherein they need to visit a physician. For treatment to be effective, physicians are in need of methods to detect OA at its earliest stages.

 

Cartilage as a whole has very little natural regenerative capacity, and cell-based or biomaterial-based strategies are still in the theoretical stage.  Current therapies for OA are primarily designed for symptom management in an attempt to improve patient mobility and quality of life and include corticosteroids, NSAIDs, DMARDs, and opioids.  Similarly, while each of the current therapies has been linked to serious side effects, toxicity, and/or efficacy plateaus, there is no current therapy capable of inducing disease remission.  As such, there is an immediate need to identify patients of OA in the early stages in order to manage the advancement of the degeneration.

 

POTENTIAL ADVANTAGES/USES: 

• Can be used to help clarify the mechanism of action of compounds already within the developmental pipeline
• Evaluation of the battery of markers could constitute the output during high throughput cell based screening
• Tissue or fluid biopsies may be screened for early stage OA
• Markers are primarily secreted soluble, receptors, or extracellular matrix factors rendering them candidate targets
• Profile may be used in the stratification of patients by stage of OA
• Profile may be used to classify or stage outcome in therapeutic rodent models of OA  

 

DEVELOPMENTAL STAGE: Preclinical proof of principle

 

Ref. #:  UWO-AH-002

 

Preclinical

US Provisional Application filed

 Available for license and/or collaborative approach.