Abstract
Therapeutic alleviation of the pathophysiology of osteoarthritis (OA) is a great and unmet medical challenge. At the basic science level, significant progress has facilitated the identification of distinct pathways and targets which appear to be central to the OA-associated deterioration of articular cartilage. For example, the dysregulated activities of aggrecanases such as ADAMTS-4 and ADAMTS-5, and collagenases such as MMP-13, point to strategies for the development of selective protease inhibitors to curtail OA disease progression. Likewise, blockade of disease-associated “pro-catabolic” cytokines may offer promising opportunities in this regard. Other novel biotherapeutic approaches are also emerging, including the use of recombinant lubricin molecules for intraarticular supplementation. Expression profiling of cartilage (and other joint tissues) to identify OA-associated genes continues to yield new potential therapeutic options, including the ‘upstream’ targeting of key intracellular regulators. Moving forward into the clinic, the critical evaluation and optimization of modalities for therapeutic delivery, as well as the availability and utility of appropriate disease biomarkers and ability to determine relevant patient populations, will be other important considerations in directing the advancement of novel OA therapies.
Keywords: Osteoarthritis, Therapeutic, Cartilage, Lubricin, Aggrecan, Aggrecanase, ADAMTS, MMP
Current Drug Targets
Title: Novel Therapies in OA
Volume: 11 Issue: 5
Author(s): Carl R. Flannery
Affiliation:
Keywords: Osteoarthritis, Therapeutic, Cartilage, Lubricin, Aggrecan, Aggrecanase, ADAMTS, MMP
Abstract: Therapeutic alleviation of the pathophysiology of osteoarthritis (OA) is a great and unmet medical challenge. At the basic science level, significant progress has facilitated the identification of distinct pathways and targets which appear to be central to the OA-associated deterioration of articular cartilage. For example, the dysregulated activities of aggrecanases such as ADAMTS-4 and ADAMTS-5, and collagenases such as MMP-13, point to strategies for the development of selective protease inhibitors to curtail OA disease progression. Likewise, blockade of disease-associated “pro-catabolic” cytokines may offer promising opportunities in this regard. Other novel biotherapeutic approaches are also emerging, including the use of recombinant lubricin molecules for intraarticular supplementation. Expression profiling of cartilage (and other joint tissues) to identify OA-associated genes continues to yield new potential therapeutic options, including the ‘upstream’ targeting of key intracellular regulators. Moving forward into the clinic, the critical evaluation and optimization of modalities for therapeutic delivery, as well as the availability and utility of appropriate disease biomarkers and ability to determine relevant patient populations, will be other important considerations in directing the advancement of novel OA therapies.
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Cite this article as:
R. Flannery Carl, Novel Therapies in OA, Current Drug Targets 2010; 11 (5) . https://dx.doi.org/10.2174/138945010791011884
DOI https://dx.doi.org/10.2174/138945010791011884 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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