Biomarkers in the Development of Novel Disease-Modifying Therapies for Osteoarthritis

Abstract

Identification and utilization of biomarkers is vitally important for the successful development of disease-modifying osteoarthritis drugs. Biochemical and imaging platforms hold great promise to deliver such biomarkers. Studies indicate a marked increase in biochemical products arising from the breakdown and biosynthesis of collagen, extracellular matrix and bone in osteoarthritis. These molecules have been associated with disease severity and may also have prognostic value as indicators of disease progression. However, issues including biological variability and lack of tissue specificity currently hinder the utility of these molecular markers in drug development. Imaging technologies hold great potential for sensitive and accurate measurement of disease-related structural damage. Drawbacks, including expense, need for validation and limited accessibility also limit the utility of these technologies. In this article, the potential value and challenges in developing and utilizing biomarkers in disease-modifying osteoarthritis drug development will be discussed.

Keywords:

• biomarkers
• cartilage metabolism
• delayed gadolinium-enhanced MRI
• disease-modifying osteoarthritis drugs
• drug development
• joint-space narrowing
• molecular imaging
• MRI
• osteoarthritis
• T1ρ magnetic resonance imaging
• translational medicine

Financial & competing interests disclosure

S Parsons, S Alesci and G Feuerstein are stock holders and employees of Wyeth Pharmaceutical; J Wang is a stock holder and an employee of Bristol-Myers Squibb, Co. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Notes

This outline denotes each biomarker‘s potential usage, as assigned by either the authors of this review or by Rousseau and Delmas [3], in parentheses, within the context of the recently proposed burden of disease, investigative, prognostic, efficacy of intervention and diagnostic (BIPED) classification of OA[4]. These assignments appear as (B), (I), (P), (E) or (D).

COMP: Cartilage oligomeric matrix protein; CPII: Carboxyl propeptide of type II collagen; CTX: Cross-linked C telopeptide; dGEMRIC: Delayed gadolinium-enhanced MRI; DPD: Deoxypyridinoline; HELIX-II: Type II collagen helical peptide; NTX: N-telopeptide of type I collagen; PIIANP: Procollagen type IIA N-propeptide; PYD: Pyridinoline; uTIINE: Type II collagen neoepitope.