Dwivedi2014 - Crohns IL6 Disease model - Anti-IL6 Antibody

ABSTRACT:

Dwivedi2014 - Crohns IL6 Disease model -Anti-IL6 Antibody

This model is comprised of four models:

• [BIOMD0000000534] Healthy Volunteer model
  
• [BIOMD0000000535] Crohn's Disease - IL-6 Antibody
  
• [BIOMD0000000536] Crohn's Disease - sgp130FC
• [BIOMD0000000537] Crohn's Disease - IL-6Ra Antibody
  

Possible avenues for Interleukin-6 (IL-6) inhibition intreating Crohn's disease are compared here. Each model refers toseparate ligands. The system simulates differential activity of theligands on the signalling of IL-6. This affects Signal Transducer and Activator ofTranscription 3 (STAT3) activity on the production ofbiomarker C-Reactive Protein (CRP) expression.
Figures referring to this Crohn's Disease model are 4a, 4b,4c and 5a.

This model is described in the article:

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 Syst Pharmacol 2014; 3: e89

Abstract:

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-6R?, or the IL-6/sIL-6R? complex are less effective at suppressing pharmacological markers of Crohn's than dual targeting the IL-6/sIL-6R? complex in addition to IL-6 or IL-6R?. 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.

This model is hosted on BioModels Database and identified by: BIOMD0000000535.

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To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

ORGANISM(S): Homo sapiens

SUBMITTER: Lucian Smith 

PROVIDER: MODEL1408050001 | biostudies-other |

SECONDARY ACCESSION(S): 24402116

REPOSITORIES: biostudies-other