ACR Meeting Abstracts

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Abstracts tagged "WNT Signaling"

  • Abstract Number: 891 • 2019 ACR/ARP Annual Meeting

    Lorecivivint (SM04690), a Potential Disease-Modifying Osteoarthritis Drug, Inhibits CLK2 and DYRK1A, Novel Molecular Regulators of Wnt Signaling, Chondrogenesis, and Inflammation

    Vishal Deshmukh1, Alyssa O'Green 1, Carine Bossard 1, Tim Seo 1, Lisa Lamangan 1, Maureen Ibanez 1, Abdullah Ghias 1, Carolyn Lai 1, Long Do 1, Shawn Cho 1, Joseph Cahiwat 1, Kevin Chiu 1, Melinda Pedraza 1 and Yusuf Yazici 1, 1Samumed, LLC, San Diego, CA

    Background/Purpose: In the synovial joint, Wnt pathway upregulation contributes to osteoarthritis (OA) by increasing osteocyte differentiation, cartilage thinning, and inflammation. Lorecivivint (LOR; SM04690), a novel…
  • Abstract Number: 1326 • 2019 ACR/ARP Annual Meeting

    Safety Profile to Date of the Novel, Intra-articular Agent Lorecivivint (LOR; SM04690), a CLK/DYRK1A Inhibitor That Modulates the Wnt Pathway, in Subjects with Knee Osteoarthritis

    Ismail Simsek 1, Chris Swearingen 1, Sarah Kennedy 1, Jeyanesh Tambiah 1, Yusuf Yazici2, Nancy Lane 3 and Marc C. Hochberg 4, 1Samumed, LLC, San Diego, 2Samumed, LLC, San Diego, CA, 3University of California at Davis Medical Center, Sacramento, CA, 4University of Maryland School of Medicine, Baltimore, MD

    Background/Purpose: Recent concerns over osteoarthritis (OA) pharmacotherapy safety have led to revision of treatment guidelines and highlight the need for therapies with good safety profiles.…
  • Abstract Number: 1327 • 2019 ACR/ARP Annual Meeting

    The Novel, Intra-articular CLK/DYRK1A Inhibitor Lorecivivint (LOR; SM04690), Which Modulates the Wnt Pathway, Improved Responder Outcomes in Subjects with Knee Osteoarthritis: A Post Hoc Analysis from a Phase 2b Trial

    Yusuf Yazici1, Sarah Kennedy 2, Chris Swearingen 2 and Jeyanesh Tambiah 2, 1Samumed, LLC, San Diego, CA, 2Samumed, LLC, San Diego

    Background/Purpose: Lorecivivint (LOR, SM04690) is a small-molecule, intra-articular (IA) CLK/DYRK1A inhibitor which modulates the Wnt pathway and has demonstrated beneficial effects on patient-reported outcomes (PROs)…
  • Abstract Number: 1435 • 2019 ACR/ARP Annual Meeting

    Acute Effects of IL-6 Blockade, TNFα Inhibitor or Glucocorticoids on Bone Turnover Markers and Wnt Inhibitors in Early Rheumatoid Arthritis

    Angelo Fassio1, GIovanni Adami 1, Ombretta Viapiana 1, Luca Idolazzi 1, Giovanni Orsolini 1, Alessandro Giollo 1, Davide Gatti 2 and Maurizio Rossini 1, 1University of Verona, Verona, Italy, 2Univerisity of Verona, Verona, Italy

    Background/Purpose: Wnt signaling is an important regulator of bone remodeling and it is involved in the pathogenesis of focal and systemic bone loss in Rheumatoid…
  • Abstract Number: 1770 • 2019 ACR/ARP Annual Meeting

    Experimental Rheumatoid Joint Ameliorated by CRISPR Interference Targeting Long Non-coding RNA H19 Through Wnt Signaling Inactivation

    Chrong-Reen Wang1, Shih-Yao Chen 1, Yu-Chi Chou 2, Chao-Liang Wu 3, Yu-Ting Lo 1 and Ai-Li Shiau 4, 1National Cheng Kung University Hospital, Tainan, Taiwan (Republic of China), 2Genomics Research Center, Academia Sinica, Taipei, Taiwan (Republic of China), 3National Cheng Kung University Medical College, Tainan, Taiwan (Republic of China), 4National Cheng Kung University Medical College, Tainan, Taiwan (Republic of China)

    Background/Purpose: Long non-coding RNAs (lncRNAs) participate in the rheumatoid arthritis (RA) pathogenesis. The aim of this study was to examine the lncRNA H19 and HOTAIR…
  • Abstract Number: L03 • 2018 ACR/ARHP Annual Meeting

    Efficacy and Safety from a Phase 2b Trial of SM04690, a Novel, Intra-Articular, Wnt Pathway Inhibitor for the Treatment of Osteoarthritis of the Knee

    Yusuf Yazici1, Timothy E. McAlindon2, Allan Gibofsky3, Nancy Lane4, Christian Lattermann5, Nebojsa Skrepnik6, Christopher Swearingen1, Anita DiFrancesco1, Jeymi Tambiah1 and Marc Hochberg7, 1Samumed, LLC, San Diego, CA, 2Division of Rheumatology, Tufts Medical Center, Boston, MA, 3Rheumatology, Weill Cornell Medicine, and Hospital for Special Surgery, New York, NY, 4Center for Musculoskeletal Health, University of California, Davis School of Medicine, Sacramento, CA, 5Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 6Tucson Orthopaedic Institute, Tucson, AZ, 7University of Maryland School of Medicine, Baltimore, MD

    Background/Purpose: A previous Phase 2a study of SM04690, a small molecule, intra-articular (IA), Wnt pathway inhibitor, demonstrated positive effects on knee OA pain, physical function,…
  • Abstract Number: 1047 • 2018 ACR/ARHP Annual Meeting

    Signaling at Adenosine A2A Receptor (A2aR) in Osteoblasts; Crosstalk with Wnt/ β-Catenin Signaling Pathway

    Soheila Borhani1, Carmen Corciulo2, Ane Larrañaga Vera3 and Bruce N. Cronstein4, 1Medicine, Division of Translational Medicine, New York University School of Medicine, New York, NY, 2Department of Medicine, Division of Rheumatology, New York University School of Medicine, New York, NY, 3Medicine, New York University School of Medicine, New York, NY, 4Rheumatology, New York University School of Medicine, Division of Rheumatology, New York, NY

    Background/Purpose: The Wnt/β-catenin signaling pathway plays a key role in regulating bone formation and maintaining bone hemostasis. Wnt activates a pathway that leads to stabilization…
  • Abstract Number: 1904 • 2018 ACR/ARHP Annual Meeting

    Orphan Nuclear Receptor Rorα Is a Key Regulator of Tgfβ- and WNT-Signaling in Fibrotic Diseases

    Rosebeth Kagwiria1, Ruifang Liang1, Alexandru Matei1, Niclas Sihler2, Chih-Wei Chen1, Thomas Burris3, Oliver Distler4, Georg Schett1 and Jörg Distler1, 1Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Department of Internal Medicine 3 – Rheumatology and Immunology, University Hospital Erlangen, Erlangen, Germany, 2Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen, Germany, 3Department of pharmacology and physiology, Saint Luis University-school of medicine, Florida, USA, St. Louis, Missouri, MO, 4Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland

    Background/Purpose: The Retinoic-acid related Orphan Receptor-alpha (RORα) is a member of the nuclear receptor superfamily and a ligand-dependent transcription factor implicated in a wide range…
  • Abstract Number: 1985 • 2018 ACR/ARHP Annual Meeting

    IL-1β Inhibits the Expression of Dickkopf-1, an Antagonist of the Wnt-β-Catenin Signaling Pathway: A Possible Role of Inflammasome in Dysregulation of Endochondral Ossification

    Satoshi Yamasaki1, Yusuke Yoshida2, Katsuhiro Oi2, Tatsuomi Kuranobu2, Takaki Nojima2, Hiroaki Ida3 and Eiji Sugiyama4, 1Division of Rheumatology, Kurume University Medical Center, Fukuoka, Japan, 2Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan, 3Respiorogy, Neurology and Rheumatology, Kurume University School of Medicine, Kurume, Japan, 4Department of Clinical Immunology and Rheumatology, Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan

    Background/Purpose: Aberrant endochondral bone formation in the physis is a unique bone lesion in neonatal-onset multisystem inflammatory disease (NOMID), also called chronic infantile neurologic cutaneous…
  • Abstract Number: 903 • 2017 ACR/ARHP Annual Meeting

    Increased Expression of CCN4/WISP1 in Osteoarthritic Articular Cartilage Is Epigenetically Regulated and Disrupts Cartilage Homeostasis

    Martijn H. van den Bosch1, Yolande F. Ramos2, Wouter den Hollander2, Nils Bömer2, Rob G. Nelissen3, Judith V. Bovée4, Peter L. van Lent1, Arjen B. Blom1, Peter M. van der Kraan1 and Ingrid Meulenbelt2, 1Experimental Rheumatology, Radboud university medical center, Nijmegen, Netherlands, 2Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands, 3Department of Orthopedics, Leiden University Medical Center, Leiden, Netherlands, 4Department of Pathology, Leiden University Medical Center, Leiden, Netherlands

    Background/Purpose: Previously, we described increased expression of Wnt-1-induced signaling protein 1 (Wisp1) in murine synovium and cartilage after induction of experimental osteoarthritis (OA) models. WISP1…
  • Abstract Number: 935 • 2017 ACR/ARHP Annual Meeting

    Results from a 52 Week Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of a Novel, Intra-Articular, Wnt Pathway Inhibitor (SM04690) for the Treatment of Knee Osteoarthritis

    Yusuf Yazici1, Timothy E. McAlindon2, Allan Gibofsky3, Nancy E. Lane4, Daniel J. Clauw5, Eddie Armas6, Nebojsa Skrepnik7, Christopher J. Swearingen1, Anita DiFrancesco1, Jeymi Tambiah1 and Marc Hochberg8, 1Samumed, LLC, San Diego, CA, 2Division of Rheumatology, Tufts Medical Center, Boston, MA, 3Rheumatology, Weill Cornell Medicine, and Hospital for Special Surgery, New York, NY, 4Center for Musculoskeletal Health, University of California at Davis, Hillsborough, CA, 5Chronic Pain & Fatigue Research Center, University of Michigan, Ann Arbor, MI, 6Well Pharma Medical Research, Miami, FL, 7Tuscon Orthopedics Institute, Tuscon, AZ, 8Head, Division of Rheumatology & Clinical Immunology; Vice Chair, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD

    Background/Purpose: Knee osteoarthritis (OA) is characterized by pain, disability and joint deformity due to articular cartilage degradation and bone remodeling. Wnt signaling is involved in…
  • Abstract Number: 1201 • 2017 ACR/ARHP Annual Meeting

    Reducing Heterogeneity in OA Clinical Trials: Data from a Phase 2 Study of SM04690, a Novel, Intra-Articular, Wnt Pathway Inhibitor in Knee Osteoarthritis

    Philip G. Conaghan1, Anita DiFrancesco2, Christopher J. Swearingen2, Sarah Kennedy2, Ismail Simsek2, Jeymi Tambiah2 and Yusuf Yazici2, 1Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom, 2Samumed, LLC, San Diego, CA

    Background/Purpose: Kellgren-Lawrence [KL] radiographic grading is used to classify knee osteoarthritis (OA), but may not accurately reflect disease progression. Classifying subjects by baseline medial joint…
  • Abstract Number: 1204 • 2017 ACR/ARHP Annual Meeting

    Radiographic Outcomes Were Associated with Pain and Function Responses: Post-Hoc Analysis of Results from a Phase 2 Study of a Small Molecule Wnt Pathway Inhibitor, SM04690, for Knee Osteoarthritis Treatment

    Yusuf Yazici1, Timothy E. McAlindon2, Allan Gibofsky3, Nancy E. Lane4, Nebojsa Skrepnik5, Eddie Armas6, Christopher J. Swearingen1, Anita DiFrancesco1, Jeymi Tambiah1 and Marc Hochberg7, 1Samumed, LLC, San Diego, CA, 2Division of Rheumatology, Tufts Medical Center, Boston, MA, 3Rheumatology, Weill Cornell Medicine, and Hospital for Special Surgery, New York, NY, 4Center for Musculoskeletal Health, University of California, Davis School of Medicine, Sacramento, CA, 5Tuscon Orthopedics Institute, Tuscon, AZ, 6Well Pharma Medical Research, Miami, FL, 7Head, Division of Rheumatology & Clinical Immunology; Vice Chair, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD

    Background/Purpose: Knee osteoarthritis (OA) is characterized by pain, disability and joint deformity due to articular cartilage degradation and bone remodeling. Wnt signaling is involved in…
  • Abstract Number: 1716 • 2017 ACR/ARHP Annual Meeting

    TGFβ-Dependent Upregulation of XIAP Fosters Fibroblast Activation and Tissue Fibrosis By Promoting Canonical Wnt Signaling

    Christina Bergmann1, Ludwig Hallenberger1, Amelie Brandt1, Benita Merlevede1, Clara Dees2, Chih-Wei Chen3, Christian Beyer1, Oliver Distler4, Georg Schett5 and Jörg Distler6, 1Department of Internal Medicine 3 and Institute for Clinical Immunology, Friedrich-Alexander-University of Erlangen-Nuremberg and University Hospital Erlangen, Erlangen, Germany, 2Department of Internal Medicine 3 and Institute for Clinical Immunology,, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany, 3Department of Internal Medicine 3 – Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen, Erlangen, Germany, Erlangen, Germany, 4Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland, 5Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen, Germany., Erlangen, Germany, 6Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany

    Background/Purpose: Aberrant activation of profibrotic pathways is a key feature of systemic sclerosis (SSc). Extensive evidence characterizes TGFβ- and canonical WNT-signaling as key drivers of…
  • Abstract Number: 1924 • 2017 ACR/ARHP Annual Meeting

    The Nuclear Receptor ROR-Alpha As a Key Checkpoint of Tissue Repair

    Rosebeth Kagwiria1, Ruifang Liang2, Chih-Wei Chen3, Thomas Burris4, Georg Schett5 and Jörg Distler6, 1Department of Internal Medicine 3 and Institute for Clinical Immunology, Friedrich-Alexander-University of Erlangen-Nuremberg and University Hospital Erlangen, Erlangen, Germany, 2Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen, Department of Internal Medicine 3 and Institute for Clinical Immunology, Friedrich-Alexander-University of Erlangen-Nuremberg and University Hospital Erlangen, Erlangen, Germany, 3Department of Internal Medicine 3 – Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and University Hospital Erlangen, Erlangen, Germany, Erlangen, Germany, 4Department of pharmacology and physiology, Saint Luis University-school of medicine, Florida, USA, St. Louis, Missouri, MO, 5Department of Internal Medicine 3 – Rheumatology and Immunology, Department of Internal Medicine 3 and Institute for Clinical Immunology, Friedrich-Alexander-University of Erlangen-Nuremberg and University Hospital Erlangen, Erlangen, Germany, 6Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany

    Background/Purpose: The Retinoic-acid related Orphan Receptor-alpha (RORα) is a member of the nuclear receptor superfamily and a ligand-dependent transcription factor implicated in a wide range…
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