Dataset Information

Dwivedi2014 - Crohns IL6 Disease model - sgp130 activity

ABSTRACT: Dwivedi2014 - Crohns IL6 Disease model - sgp130 activity 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 in treating Crohn's disease are compared here. Each model refers to separate ligands. The system simulates differential activity of the ligands on the signalling of IL-6. This affects Signal Transducer and Activator of Transcription 3 (STAT3) activity on the production of biomarker C-Reactive Protein (CRP) expression. The figure referring to this Crohn's Disease model is 6b. 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: BIOMD0000000536. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. 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.

DISEASE(S): Crohn's Disease

SUBMITTER: Vincent Knight-Schrijver

PROVIDER: BIOMD0000000536 | BioModels | 2024-09-02

REPOSITORIES: BioModels

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	BIOMD0000000536?filename=BIOMD0000000536-biopax2.owl	Owl
	BIOMD0000000536?filename=BIOMD0000000536-biopax3.owl	Owl
	BIOMD0000000536?filename=BIOMD0000000536.m	Other
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Publications

A multiscale model of interleukin-6-mediated immune regulation in Crohn's disease and its application in drug discovery and development.

Dwivedi G G Fitz L L Hegen M M Martin S W SW Harrold J J Heatherington A A Li C C

CPT: pharmacometrics & systems pharmacology 20140108

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 devel ...[more]

PMID: 24402116

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Project description:Dwivedi2014 - Crohns IL6 Disease model - Anti-IL6R 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 in treating Crohn's disease are compared here. Each model refers to separate ligands. The system simulates differential activity of the ligands on the signalling of IL-6. This affects Signal Transducer and Activator of Transcription 3 (STAT3) activity on the production of biomarker C-Reactive Protein (CRP) expression. Figures referring to this Crohn's Disease model are 3a, 4d, 4e, 4f and 5b. 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: BIOMD0000000537. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. 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.

Project description: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 in treating Crohn's disease are compared here. Each model refers to separate ligands. The system simulates differential activity of the ligands on the signalling of IL-6. This affects Signal Transducer and Activator of Transcription 3 (STAT3) activity on the production of biomarker 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. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. 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.

Project description:Dwivedi2014 - Healthy Volunteer IL6 Model 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 in treating Crohn's disease are compared here. Each model refers to separate ligands. The system simulates differential activity of the ligands on the signalling of IL-6. This affects Signal Transducer and Activator of Transcription 3 (STAT3) activity on the production of biomarker C-Reactive Protein (CRP) expression. Figures referring to this Healthy Volunteer model are 2c and 2d. 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: BIOMD0000000534. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. 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.