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Experimental models of cortical multiple sclerosis pathology
Publication date: Available online 11 October 2018Source: Drug Discovery Today: Disease ModelsAuthor(s): Maarten E. Witte, Jack van HorssenGrey matter tissue damage is a characteristic pathological hallmark of multiple sclerosis. Although evidence is emerging that cortical atrophy is strongly associated with sustained disease progression, the underlying pathological processes that contribute to neurodegeneration remain poorly understood. One reason for this is that key features of progressive MS, such as cortical demyelination, microglial cell activation and neurodegeneration are absent in most of the commonly used rodent ...
Source: Drug Discovery Today: Disease Models - October 12, 2018 Category: Drugs & Pharmacology Source Type: research

Editorial to “Evaluating biomaterials and implanted devices”
Publication date: Summer 2017Source: Drug Discovery Today: Disease Models, Volume 24Author(s): Roberto Gaetani, Karen L. Christman (Source: Drug Discovery Today: Disease Models)
Source: Drug Discovery Today: Disease Models - September 22, 2018 Category: Drugs & Pharmacology Source Type: research

Models for evaluating the immune response to naturally derived biomaterials
Publication date: Available online 2 August 2018Source: Drug Discovery Today: Disease ModelsAuthor(s): Jenna L. Dziki, Stephen F. BadylakThe immune response to biomaterials has emerged as a critical determinant of tissue repair outcomes and is complex, involving multiple cell types, distinct spatiotemporal phenotypes, and is influenced by variables including processing of the material and host-related factors. This interaction between implanted material and the host immune cells has stimulated interest in analytical methods to characterize the immune response. The present review discusses these methods including in vitro, ...
Source: Drug Discovery Today: Disease Models - August 3, 2018 Category: Drugs & Pharmacology Source Type: research

Humanized mouse model for evaluating biocompatibility and human immune cell interactions to biomaterials
Publication date: Available online 17 July 2018Source: Drug Discovery Today: Disease ModelsAuthor(s): Raymond M. Wang, Jingjin He, Yang Xu, Karen L. ChristmanImmune system humanized mice provide unique platforms for improving preclinical evaluation of the human immune response to novel biomaterial therapies. Wild-type animals and human immune cell in vitro cultures provide limited representation of the human immune response, leading to unexpected responses to therapies in human patients. Introducing human tissue, cells, and genes into immunodeficient mice have advanced these animal models to reconstitute multiple lineages ...
Source: Drug Discovery Today: Disease Models - July 18, 2018 Category: Drugs & Pharmacology Source Type: research

Large animal models to test mechanical circulatory support devices
Publication date: Available online 13 July 2018Source: Drug Discovery Today: Disease ModelsAuthor(s): Takuma Miyamoto, Jamshid H. Karimov, Andrew Xanthopoulos, Randall C. Starling, Kiyotaka FukamachiMechanical circulatory support (MCS) devices are widely used to treat patients with heart failure. Animal studies have been essential to the development of MCS devices. A number of factors must be considered to ensure good results from these experiments. In this review, we discuss current debates on what might be the ideal surgical approach to evaluating MCS devices in large animals, the hemodynamic and laboratory differences b...
Source: Drug Discovery Today: Disease Models - July 14, 2018 Category: Drugs & Pharmacology Source Type: research

Computational models of blood disorders
Publication date: Available online 20 February 2016Source: Drug Discovery Today: Disease ModelsAuthor(s): George Em Karniadakis (Source: Drug Discovery Today: Disease Models)
Source: Drug Discovery Today: Disease Models - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Modeling approaches for hepatic spatial heterogeneity in pharmacokinetic simulations
Publication date: Winter 2016Source: Drug Discovery Today: Disease Models, Volume 22Author(s): Lars Ole Schwen, Lars Kuepfer, Tobias PreusserThe metabolization and excretion of drugs in the liver are spatially heterogeneous processes. This is due to the spatial variability of physiological processes at different length scales of biological organization in healthy individuals, while many liver diseases further contribute to the heterogeneity. Classical, well-stirred pharmacokinetic models do not represent this heterogeneity, and various modeling approaches capable of representing heterogeneity have been developed recently. ...
Source: Drug Discovery Today: Disease Models - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Computational modelling of Hedgehog signalling in liver regeneration
Publication date: Winter 2016Source: Drug Discovery Today: Disease Models, Volume 22Author(s): Madlen Matz-SojaOrgan regeneration is a very complex process that includes not only the reconstruction of organ mass but also the reorganisation of homeostatic capabilities. This especially applies for the liver, which performs a variety of metabolic functions. In the last decade, morphogenic pathways such as the Wnt/β-Catenin and Hedgehog signalling pathways have been revealed to orchestrate liver regeneration as well as metabolism. Mathematical models have been successfully applied to liver regeneration, but these have not int...
Source: Drug Discovery Today: Disease Models - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Virtual liver models in pre-surgical planning, intra-surgical navigation and prognosis analysis
Publication date: Winter 2016Source: Drug Discovery Today: Disease Models, Volume 22Author(s): Harvey Ho, Adam Bartlett, Peter HunterMajor liver resection (hepatectomy) is required for patients with liver metastasis (e.g., from colorectal cancer) and hepatocellular carcinoma (e.g., from chronic hepatitis B infection). Hepatectomy is based principally on the segmental anatomy of the liver, which has few reliable external landmarks to orientate the surgeon. Anatomical variations are common and significant flow alterations after surgery are thought to be a cause for liver dysfunction. Live donor liver transplants (LDLT) are b...
Source: Drug Discovery Today: Disease Models - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Reverse engineering the inflammatory “clock”: from computational modeling to rational resetting
Publication date: Winter 2016Source: Drug Discovery Today: Disease Models, Volume 22Author(s): Yoram VodovotzProperly-regulated inflammation is central to homeostasis, and becomes dysregulated after traumatic injury, hemorrhage, and sepsis. Inflammation is a dynamic, complex system whose function, like that of an analog clock, cannot be discerned simply from a laundry list of its parts (data). Dynamic approaches to data-driven computational modeling can be thought of as the “gears” and “hands” of the “clock,” and have led to insights regarding principal drivers, dynamic networks, feedbacks, and regulatory switc...
Source: Drug Discovery Today: Disease Models - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Editorial to “Computational models of liver disease 2016”
Publication date: Winter 2016Source: Drug Discovery Today: Disease Models, Volume 22Author(s): Adriano M. Henney (Source: Drug Discovery Today: Disease Models)
Source: Drug Discovery Today: Disease Models - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Development of quantitative systems pharmacology and toxicology models within consortia: experiences and lessons learned through DILIsym development
This article highlights lessons learned from past experiences associated with The DILI-sim Initiative – a collaborative effort focused on developing DILIsym software for predicting drug-induced liver injury (DILI). (Source: Drug Discovery Today: Disease Models)
Source: Drug Discovery Today: Disease Models - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Assessing interindividual variability by Bayesian-PBPK modeling
Publication date: Winter 2016Source: Drug Discovery Today: Disease Models, Volume 22Author(s): Markus Krauss, Andreas SchuppertThe description of interindividual variability and the ADME-related sources of such variability (ADME: absorption, distribution, metabolization, excretion) is an essential element in clinical drug development to identify potentially relevant subgroups of non-responders or high-risk patients. The use of physiologically-based pharmacokinetic (PBPK) models supports a mechanistic understanding of the underlying ADME processes related to drug pharmacokinetics. In addition, the integration of Bayesian st...
Source: Drug Discovery Today: Disease Models - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Towards knowledge-driven cross-species extrapolation
Publication date: Winter 2016Source: Drug Discovery Today: Disease Models, Volume 22Author(s): Christoph Thiel, Ute Hofmann, Ahmed Ghallab, Rolf Gebhardt, Jan G. Hengstler, Lars KuepferThe transition from preclinical research to clinical phases is a crucial step in pharmaceutical development. In phase I, a new molecular entity is for the first administered to humans, after year-long development in in vitro and in preclinical animal models. However, a significant number of projects is closed during such first-in-man trials, mostly due to reasons of toxicity. This requires for new approaches in pharmaceutical development thr...
Source: Drug Discovery Today: Disease Models - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Systems pharmacology of hepatic metabolism in zebrafish larvae
Publication date: Winter 2016Source: Drug Discovery Today: Disease Models, Volume 22Author(s): Rob C. van Wijk, Elke H.J. Krekels, Thomas Hankemeier, Herman P. Spaink, Piet H. van der GraafInterspecies translation of pharmacological processes needs to improve to reduce attrition in drug development. Systems pharmacology integrates systems biology and pharmacometrics to characterise and quantify system-specific behaviour upon exposure to drugs in different species. The zebrafish is a suitable vertebrate model organism for systems pharmacology, combining high-throughput potential with high genetic homology to higher vertebra...
Source: Drug Discovery Today: Disease Models - July 10, 2018 Category: Drugs & Pharmacology Source Type: research