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Overview of 3Rs opportunities in drug discovery and development using non-human primates
Publication date: Spring 2017Source: Drug Discovery Today: Disease Models, Volume 23Author(s): Helen Prior, Fiona Sewell, Jane StewartNon-human primates (NHPs) are included within safety testing programmes for potential new medicines when justified as the relevant species for use. Although the NHP is often the only relevant species for the testing of large molecule biotherapeutics, a proportion of small molecule compounds may also require testing in NHPs, when other non-rodent species are unsuitable. Whilst the toxicology studies continue to be required for regulatory submissions, there are opportunities to both reduce the...
Source: Drug Discovery Today: Disease Models - July 5, 2018 Category: Drugs & Pharmacology Source Type: research

Non-human primate models and in vitro liver stage cultures as alternatives in malaria drug development
Publication date: Spring 2017Source: Drug Discovery Today: Disease Models, Volume 23Author(s): Anne-Marie Zeeman, Clemens H.M. KockenNon-human primates (NHP) have been used extensively in the identification of new antimalarial compounds. Especially the Plasmodium cynomolgi/rhesus monkey model was a very popular substitute to evaluate compounds for P. vivax liver- and blood stages. Nowadays we have replaced, as much as possible, the NHP in vivo testing with in vitro assays. In this review, an overview is given on malaria drug testing in NHP, the development of the in vitro models and especially the in vitro hypnozoite assay...
Source: Drug Discovery Today: Disease Models - July 5, 2018 Category: Drugs & Pharmacology Source Type: research

In vitro and in vivo models for assessing the host response to biomaterials
Publication date: Available online 18 May 2018Source: Drug Discovery Today: Disease ModelsAuthor(s): Leila S. Saleh, Stephanie J. BryantThe foreign body response (FBR) occurs ubiquitously to essentially all non-biological materials that are implanted into higher organisms. The FBR is characterized by inflammation followed by fibrosis and is mediated largely by macrophages. While many current medical devices tolerate the FBR, the FBR is responsible for many asceptic device failures and is hindering advancements of new devices that rely on device-host communication to function. To this end, in vitro and in vivo models are cr...
Source: Drug Discovery Today: Disease Models - July 5, 2018 Category: Drugs & Pharmacology Source Type: research

Animal models for heart valve research and development
Publication date: Available online 28 May 2018Source: Drug Discovery Today: Disease ModelsAuthor(s): Arash Kheradvar, Ramin Zareian, Shimako Kawauchi, Richard L. Goodwin, Sandra RugonyiValvular heart disease is the third-most common cause of heart problems in the United States. Malfunction of the valves can be acquired or congenital and each may lead either to stenosis or regurgitation, or even both in some cases. Heart valve disease is a progressive disease, which is irreversible and may be fatal if left untreated. Medications cannot currently prevent valvular calcification or help repair damaged valves, as valve tissue i...
Source: Drug Discovery Today: Disease Models - July 5, 2018 Category: Drugs & Pharmacology Source Type: research

Animal models of cardiovascular disease as test beds of bioengineered vascular grafts
Publication date: Available online 18 June 2018Source: Drug Discovery Today: Disease ModelsAuthor(s): Sindhu Row, Daniel D. Swartz, Stelios T. AndreadisThe last two decades have seen many advances in regenerative medicine, including the development of tissue engineered vessels (TEVs) for replacement of damaged or diseased arteries or veins. Biomaterials from natural sources, as well as synthetic polymeric materials have been employed in engineering vascular grafts. Recently, cell-free grafts have become available, opening new possibilities for the next generation, off-the-shelf products. These TEVs are first tested in smal...
Source: Drug Discovery Today: Disease Models - July 5, 2018 Category: Drugs & Pharmacology Source Type: research

Animal models of vascular stenting
Publication date: Available online 20 June 2018Source: Drug Discovery Today: Disease ModelsAuthor(s): Laura E. Leigh PerkinsThroughout the 30-year history of vascular stents, from their initial conception to current drug-eluting and bioresorbable technologies, animal models have played an instrumental role in the development of vascular stents. From rodents to rabbits, dogs, sheep, and swine, a variety of animal models for the evaluation of vascular stents exist, each being balanced with a unique set of advantages and shortcomings. With the appropriate selection of species and anatomy, animal models can be used to provide ...
Source: Drug Discovery Today: Disease Models - July 5, 2018 Category: Drugs & Pharmacology Source Type: research

Non-human primate models and in vitro liver stage cultures as alternatives in malaria drug development
Publication date: Available online 30 March 2018 Source:Drug Discovery Today: Disease Models Author(s): Anne-Marie Zeeman, Clemens H.M. Kocken Non-human primates (NHP) have been used extensively in the identification of new antimalarial compounds. Especially the Plasmodium cynomolgi/rhesus monkey model was a very popular substitute to evaluate compounds for P. vivax liver- and blood stages. Nowadays we have replaced, as much as possible, the NHP in vivo testing with in vitro assays. In this review, an overview is given on malaria drug testing in NHP, the development of the in vitro models and especially the in vitro hy...
Source: Drug Discovery Today: Disease Models - March 31, 2018 Category: Drugs & Pharmacology Source Type: research

Non-human primates are essential models in the translational research of multiple sclerosis
Publication date: Available online 3 February 2018 Source:Drug Discovery Today: Disease Models Author(s): Bert A. ‘t Hart, Che Serguera, Yolanda S. Kap, Bruno Gran Ageing Western societies are facing an increasing prevalence of chronic inflammatory and degenerative diseases for which no effective treatments exist. The pressure on the drug development industry to develop such treatments creates a need for translationally relevant animal models, which faithfully replicate essential pathogenic mechanisms of the human disease. In this Short Review, we discuss the essential role of the non-human primate (NHP) in the tra...
Source: Drug Discovery Today: Disease Models - February 15, 2018 Category: Drugs & Pharmacology Source Type: research

Measles: What we have learned from non-human primate models
Publication date: Available online 12 February 2018 Source:Drug Discovery Today: Disease Models Author(s): Rik L. de Swart Studies in non-human primates (NHPs) have been crucial for our understanding of measles as a high impact viral disease of humans. Over a century ago, inoculations of NHPs with filtered secretions from measles patients first identified a virus as the causative agent of this disease. In the 1960s, studies in NHPs with measles virus isolates passaged in vitro provided the basis for live-attenuated measles virus vaccines, which became one of the most successful medical interventions in history. More rec...
Source: Drug Discovery Today: Disease Models - February 15, 2018 Category: Drugs & Pharmacology Source Type: research

Editorial to “Novel development in mouse phenotyping 2014”
Publication date: Summer 2016 Source:Drug Discovery Today: Disease Models, Volume 20 Author(s): Steve Brown (Source: Drug Discovery Today: Disease Models)
Source: Drug Discovery Today: Disease Models - December 16, 2017 Category: Drugs & Pharmacology Source Type: research

Editorial DDT: Cancer models in drug development
Publication date: Autumn 2016 Source:Drug Discovery Today: Disease Models, Volume 21 Author(s): Robert M. Mader (Source: Drug Discovery Today: Disease Models)
Source: Drug Discovery Today: Disease Models - December 16, 2017 Category: Drugs & Pharmacology Source Type: research

Virtual liver models in pre-surgical planning, intra-surgical navigation and prognosis analysis
Publication date: Winter 2016 Source:Drug Discovery Today: Disease Models, Volume 22 Author(s): Harvey Ho, Adam Bartlett, Peter Hunter Major 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...
Source: Drug Discovery Today: Disease Models - December 16, 2017 Category: Drugs & Pharmacology Source Type: research

Modeling approaches for hepatic spatial heterogeneity in pharmacokinetic simulations
Publication date: Winter 2016 Source:Drug Discovery Today: Disease Models, Volume 22 Author(s): Lars Ole Schwen, Lars Kuepfer, Tobias Preusser The 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 rec...
Source: Drug Discovery Today: Disease Models - December 16, 2017 Category: Drugs & Pharmacology Source Type: research

Assessing interindividual variability by Bayesian-PBPK modeling
Publication date: Winter 2016 Source:Drug Discovery Today: Disease Models, Volume 22 Author(s): Markus Krauss, Andreas Schuppert The 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 Bayes...
Source: Drug Discovery Today: Disease Models - December 16, 2017 Category: Drugs & Pharmacology Source Type: research

Editorial to “Computational models of liver disease 2016”
Publication date: Winter 2016 Source:Drug Discovery Today: Disease Models, Volume 22 Author(s): Adriano M. Henney (Source: Drug Discovery Today: Disease Models)
Source: Drug Discovery Today: Disease Models - December 16, 2017 Category: Drugs & Pharmacology Source Type: research