ArticleOsteoarthritis and cartilage2015
Translational development of an ADAMTS-5 antibody for osteoarthritis disease modification.
Article in Osteoarthritis and cartilage, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
73 citing papers in PubMed, 114 citations in OpenAlex.
- Biomimetic cellular sponges for neutralizing inflammatory cytokines in osteoarthritic joints.Materials today. Bio · 2026Article
- ADAM and ADAMTS proteases as integrative hubs in heart failure pathogenesis and therapy.iScience · 2026Review
- Knockin expression of human ADAMTS5 impairs cardiovascular development and aggravates cerebral cavernous malformations in mice.Disease models & mechanisms · 2026Article
- An Overview of ADAMTS Proteases.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Paeoniflorin-loaded MBG nanogel alleviates oxidative microenvironment and reinforces subchondral bone regeneration for osteoarthritis treatment.Regenerative biomaterials · 2026Article
- Design, synthesis and biological activity of glycoconjugated ADAMTS5 exosite inhibitors: applications in osteoarthritis and ovarian cancer models.Scientific reports · 2025Article
- Osteoarthritis: Mechanisms and Therapeutic Advances.MedComm · 2025Review
- The Impact of Selenium Deficiency and T-2 Toxin on Zip6 Expression in Kashin-Beck Disease.Biological trace element research · 2025Article
- Antibody and aptamer-based therapies for osteoarthritis: Application of antibodies and promise of aptamers.Molecular therapy. Nucleic acids · 2025Review
- Cleavage of Cartilage Oligomeric Matrix Protein (COMP) by ADAMTS4 generates a neoepitope associated with osteoarthritis and other forms of degenerative joint disease.Matrix biology : journal of the International Society for Matrix Biology · 2025Article
- AM1241 inhibits chondrocyte inflammation and ECM degradation through the Nrf2/HO-1 and NF-κB pathways and alleviates osteoarthritis in mice.Molecular medicine (Cambridge, Mass.) · 2025Article
- Combined genetic-pharmacologic inactivation of tightly linked ADAMTS proteases in temporally specific windows uncovers distinct roles for versican proteolysis and glypican-6 in cardiac development.Matrix biology : journal of the International Society for Matrix Biology · 2024Article
- TBK1 pharmacological inhibition mitigates osteoarthritis through attenuating inflammation and cellular senescence in chondrocytes.Journal of orthopaedic translation · 2024Article
- A brief review of current treatment options for osteoarthritis including disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics.Annals of medicine and surgery (2012) · 2024Review
- Safety, Tolerability, and Pharmacodynamics of the ADAMTS-5 Nanobody M6495: Two Phase 1, Single-Center, Double-Blind, Randomized, Placebo-Controlled Studies in Healthy Subjects and Patients With Osteoarthritis.ACR open rheumatology · 2024Article
- Inhibition of HOXD11 promotes cartilage degradation and induces osteoarthritis development.Journal of orthopaedic surgery and research · 2024Article
- The Role of Genetics and Epigenetic Regulation in the Pathogenesis of Osteoarthritis.International journal of molecular sciences · 2023Review
- Development of Selective ADAMTS-5 Peptide Substrates to Monitor Proteinase Activity.Journal of medicinal chemistry · 2023Article
- Latest insights in disease-modifying osteoarthritis drugs development.Therapeutic advances in musculoskeletal disease · 2023Review
- Natural Compounds: Potential Therapeutics for the Inhibition of Cartilage Matrix Degradation in Osteoarthritis.Life (Basel, Switzerland) · 2022Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
OBJECTIVE/
methodAggrecanase activity, most notably ADAMTS-5, is implicated in pathogenic cartilage degradation. Selective monoclonal antibodies (mAbs) to both ADAMTS-5 and ADAMTS-4 were generated and in vitro, ex vivo and in vivo systems were utilized to assess target engagement, aggrecanase inhibition and modulation of disease-related endpoints with the intent of selecting a candidate for clinical development in osteoarthritis (OA).
resultsStructural mapping predicts the most potent mAbs employ a unique mode of inhibition by cross-linking the catalytic and disintegrin domains. In a surgical mouse model of OA, both ADAMTS-5 and ADAMTS-4-specific mAbs penetrate cartilage following systemic administration, demonstrating access to the anticipated site of action. Structural disease modification and associated alleviation of pain-related behavior were observed with ADAMTS-5 mAb treatment. Treatment of human OA cartilage demonstrated a preferential role for ADAMTS-5 inhibition over ADAMTS-4, as measured by ARGS neoepitope release in explant cultures. ADAMTS-5 mAb activity was most evident in a subset of patient-derived tissues and suppression of ARGS neoepitope release was sustained for weeks after a single treatment in human explants and in cynomolgus monkeys, consistent with high affinity target engagement and slow ADAMTS-5 turnover.
conclusionThis data supports a hypothesis set forth from knockout mouse studies that ADAMTS-5 is the major aggrecanase involved in cartilage degradation and provides a link between a biological pathway and pharmacology which translates to human tissues, non-human primate models and points to a target OA patient population. Therefore, a humanized ADAMTS-5-selective monoclonal antibody (GSK2394002) was progressed as a potential OA disease modifying therapeutic.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.