Abstract
Osteoarthritis (OA) is a slowly, progressive, ultimately degenerative disorder of movable joints, mainly characterized by joint pain and functional limitation and affecting all joint structures not just articular cartilage, but also the subchondral bone, ligaments, capsule, synovial membrane, and menisci. OA occurs when the equilibrium between breakdown and repair of the joint tissues becomes unbalanced. There are currently no pharmacological interventions available to patients for modifying the underlying disease (DMOADs) in relation to major drug development challenges. The current regulatory draft guidances for clinical development programs for DMOAD agents suggest radiographic joint space narrowing (JSN) as a primary endpoint. However, research efforts must continue to characterize imaging alternatives with greater sensitivity to change to enable development of new DMOADs. Past experience with DMOAD clinical trials indicate that pharmacologic agents must demonstrate pristine safety, and that consideration for special populations is important to avoid failed studies. More research is needed to determine what constitutes clinically meaningfulness for DMOAD activity in particular as it relates to OA progression. Current research pursues a variety of molecular targets including anti-catabolic agents to slow or halt OA progression and anabolic drugs to induce cartilage regrowth.
Keywords: Osteoarthritis, structural progression, DMOADs, molecular targets
Current Drug Targets
Title: Disease Modifying Osteoarthritis Drugs: Facing Development Challenges and Choosing Molecular Targets
Volume: 11 Issue: 5
Author(s): Marie-Pierre Hellio Le Graverand-Gastineau
Affiliation:
Keywords: Osteoarthritis, structural progression, DMOADs, molecular targets
Abstract: Osteoarthritis (OA) is a slowly, progressive, ultimately degenerative disorder of movable joints, mainly characterized by joint pain and functional limitation and affecting all joint structures not just articular cartilage, but also the subchondral bone, ligaments, capsule, synovial membrane, and menisci. OA occurs when the equilibrium between breakdown and repair of the joint tissues becomes unbalanced. There are currently no pharmacological interventions available to patients for modifying the underlying disease (DMOADs) in relation to major drug development challenges. The current regulatory draft guidances for clinical development programs for DMOAD agents suggest radiographic joint space narrowing (JSN) as a primary endpoint. However, research efforts must continue to characterize imaging alternatives with greater sensitivity to change to enable development of new DMOADs. Past experience with DMOAD clinical trials indicate that pharmacologic agents must demonstrate pristine safety, and that consideration for special populations is important to avoid failed studies. More research is needed to determine what constitutes clinically meaningfulness for DMOAD activity in particular as it relates to OA progression. Current research pursues a variety of molecular targets including anti-catabolic agents to slow or halt OA progression and anabolic drugs to induce cartilage regrowth.
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Hellio Le Graverand-Gastineau Marie-Pierre, Disease Modifying Osteoarthritis Drugs: Facing Development Challenges and Choosing Molecular Targets, Current Drug Targets 2010; 11 (5) . https://dx.doi.org/10.2174/138945010791011893
DOI https://dx.doi.org/10.2174/138945010791011893 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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