TY  - JOUR
A1  - Stübler, Sabine
A1  - Kloft, Charlotte
A1  - Huisinga, Wilhelm
T1  - Cell-level systems biology model to study inflammatory bowel diseases and their treatment options
T2  - CPT: pharmacometrics & systems pharmacology
N2  - To help understand the complex and therapeutically challenging inflammatory bowel diseases (IBDs), we developed a systems biology model of the intestinal immune system that is able to describe main aspects of IBD and different treatment modalities thereof. The model, including key cell types and processes of the mucosal immune response, compiles a large amount of isolated experimental findings from literature into a larger context and allows for simulations of different inflammation scenarios based on the underlying data and assumptions. In the context of a large and diverse virtual IBD population, we characterized the patients based on their phenotype (in contrast to healthy individuals, they developed persistent inflammation after a trigger event) rather than on a priori assumptions on parameter differences to a healthy individual. This allowed to reproduce the enormous diversity of predispositions known to lead to IBD. Analyzing different treatment effects, the model provides insight into characteristics of individual drug therapy. We illustrate for anti-TNF-alpha therapy, how the model can be used (i) to decide for alternative treatments with best prospects in the case of nonresponse, and (ii) to identify promising combination therapies with other available treatment options.
Y1  - 2023
UR  - https://publishup.uni-potsdam.de/frontdoor/index/index/docId/64396
SN  - 2163-8306
VL  - 12
IS  - 5
SP  - 690
EP  - 705
PB  - Nature Publ. Group
CY  - London
ER  -