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Dwivedi2014 - Crohns IL6 Disease model - sgp130 activity

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Short description
Format
SBML (L2V4)
Related Publication
  • A multiscale model of interleukin-6-mediated immune regulation in Crohn's disease and its application in drug discovery and development.
  • Dwivedi G, Fitz L, Hegen M, Martin SW, Harrold J, Heatherington A, Li C
  • CPT: pharmacometrics & systems pharmacology , 0/ 2014 , Volume 3 , pages: e89
  • The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
  • In this study, we have developed a multiscale systems model of interleukin (IL)-6-mediated immune regulation in Crohn's disease, by integrating intracellular signaling with organ-level dynamics of pharmacological markers underlying the disease. This model was linked to a general pharmacokinetic model for therapeutic monoclonal antibodies and used to comparatively study various biotherapeutic strategies targeting IL-6-mediated signaling in Crohn's disease. Our work illustrates techniques to develop mechanistic models of disease biology to study drug-system interaction. Despite a sparse training data set, predictions of the model were qualitatively validated by clinical biomarker data from a pilot trial with tocilizumab. Model-based analysis suggests that strategies targeting IL-6, IL-6Rα, or the IL-6/sIL-6Rα complex are less effective at suppressing pharmacological markers of Crohn's than dual targeting the IL-6/sIL-6Rα complex in addition to IL-6 or IL-6Rα. The potential value of multiscale system pharmacology modeling in drug discovery and development is also discussed.CPT: Pharmacometrics & Systems Pharmacology (2014) 3, e89; doi:10.1038/psp.2013.64; advance online publication 8 January 2014.
Contributors
administrator, Vincent Knight-Schrijver

Metadata information

Curation status
Curated
Name Description Size Actions

Model files

BIOMD0000000536.xml.origin SBML L2V4 representation of Dwivedi2014 - Crohns IL6 Disease model - sgp130 activity 162.95 KB Preview | Download

Additional files

Dwivedi2014_IL6_sgp130_activity_log.txt.zip Curation log.txt file summarising all changes made to original model. Includes details of figure reproduction. 1.40 KB Preview | Download

  • Model originally submitted by : Vincent Knight-Schrijver
  • Submitted: Aug 5, 2014 1:55:21 PM
  • Last Modified: Dec 21, 2018 5:28:52 PM
Revisions
  • Version: 3 public model Download this version
    • Submitted on: Dec 21, 2018 5:28:52 PM
    • Submitted by: administrator
    • With comment: Include the additional files provided by the submitter in the original submission: Dwivedi2014_IL6_sgp130_activity_log.txt.zip
  • Version: 2 public model Download this version
    • Submitted on: Jan 13, 2017 4:04:04 PM
    • Submitted by: Vincent Knight-Schrijver
    • With comment: Current version of Dwivedi2014 - Crohns IL6 Disease model - sgp130 activity
  • Version: 1 public model Download this version
    • Submitted on: Aug 5, 2014 1:55:21 PM
    • Submitted by: Vincent Knight-Schrijver
    • With comment: Original import of Dwivedi2014 - Crohns IL6 Disease model - sgp130 activity
Curator's comment:
(added: 06 Aug 2014, 12:29:53, updated: 06 Aug 2014, 12:29:53)
Figure 6b: Suppression of CRP after 12 weeks of sgp130Fc administration. Separate curves represent timing between doses. sgp130Fc is an antibody modified with sgp130, an endogenous Inhibitor and sequestration glycoprotein of the IL6/IL6Ra soluble complex. Three separate simulations, one for each dose regimen, were carried out by parameter scan for Dose with 8 intervals between 0 and 2000 mg. Results plotted in libreCalc.