scholarly journals A standardised framework to identify optimal animal models for efficacy assessment in drug development

2018 ◽  
Author(s):  
Guilherme S. Ferreira ◽  
Désirée Veening-Griffioen ◽  
Wouter Boon ◽  
Ellen Moors ◽  
Christine Gispen-de Wied ◽  
...  
Keyword(s):  
Animal Models ◽  
Drug Development ◽  
Internal Validity ◽  
Diabetes Type 2 ◽  
Human Condition ◽  
Mdx Mouse ◽  
Published Data ◽  
Drug Candidates ◽  
Zdf Rat ◽  
Key Aspects

AbstractIntroductionPoor translation of efficacy data derived from animal models is a potential contributor to costly and unnecessary attrition in clinical trials.ObjectivesTo develop a tool to assess, validate and compare the clinical translatability of animal models used for the preliminary assessment of efficacy.Design and ResultsWe conducted an exploratory literature search to identify the key aspects to validate animal models. Eight aspects (Epidemiology, Pathophysiology, Genetic, Biochemistry, Aetiology, Histology, Pharmacology and Endpoints) were identified for which questions were drafted to evaluate the different faces of the human disease simulation. Features of the framework include standardised instructions, a weighting and scoring system to compare models as well as contextualising factors regarding model similarity and evidence uncertainty. We included a quality assessment of the internal validity of drug intervention studies included in the Pharmacological validation section for both effective and ineffective drugs in humans. A web-based survey was conducted with experts from different stakeholders to gather input on the framework. Finally, we present a case study of a preliminary validation and comparison of two animal models for Duchenne Muscular Dystrophy (mdx mouse and GRMD dog) and Diabetes Type 2 (ZDF rat and db/db mouse). We show that there are significant differences between the mdx mouse and the GRMD dog, the latter mimicking the human condition to a greater extent than the mouse despite the considerable lack of published data. In DT2, both the ZDF rat and the db/db mouse are comparable with minor differences in pathophysiology.ConclusionsFIMD facilitates drug development by serving as the basis to select the most relevant model that can provide meaningful and translatable results to progress drug candidates to the clinic.

scholarly journals Future Perspective of Diabetic Animal Models

2020 ◽  
Vol 20 (1) ◽  
pp. 25-38
Author(s):  
Shashank Pandey ◽  
Magdalena C. Dvorakova
Keyword(s):  
Animal Models ◽  
Diabetic Animal ◽  
Future Perspective ◽  
Published Data ◽  
Drug Candidates ◽  
Zdf Rat ◽  
Nonobese Diabetic ◽  
Diabetic Model ◽  
Biobreeding Rat ◽  
Genetic And Environmental Factors

Objective: The need of today’s research is to develop successful and reliable diabetic animal models for understanding the disease susceptibility and pathogenesis. Enormous success of animal models had already been acclaimed for identifying key genetic and environmental factors like Idd loci and effects of microorganisms including the gut microbiota. Furthermore, animal models had also helped in identifying many therapeutic targets and strategies for immune-intervention. In spite of a quite success, we have acknowledged that many of the discovered immunotherapies are working on animals and did not have a significant impact on human. Number of animal models were developed in the past to accelerate drug discovery pipeline. However, due to poor initial screening and assessment on inequivalent animal models, the percentage of drug candidates who succeeded during clinical trials was very low. Therefore, it is essential to bridge this gap between pre-clinical research and clinical trial by validating the existing animal models for consistency. Results and Conclusion: In this review, we have discussed and evaluated the significance of animal models on behalf of published data on PUBMED. Amongst the most popular diabetic animal models, we have selected six animal models (e.g. BioBreeding rat, “LEW IDDM rat”, “Nonobese Diabetic (NOD) mouse”, “STZ RAT”, “LEPR Mouse” and “Zucker Diabetic Fatty (ZDF) rat” and ranked them as per their published literature on PUBMED. Moreover, the vision and brief imagination for developing an advanced and robust diabetic model of 21st century was discussed with the theme of one miceone human concept including organs-on-chips.

Recent advances in animal model experimentation in autism research

2013 ◽  
Vol 26 (5) ◽  
pp. 264-271 ◽  
Author(s):  
Mousumi Tania ◽  
Md. Asaduzzaman Khan ◽  
Kun Xia
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Human Condition ◽  
Behavioral Alterations ◽  
Important Place ◽  
Adult Mice ◽  
Recent Advances ◽  
Model Study ◽  
Disease Biology ◽  
Animal Model Study

ObjectiveAutism, a lifelong neuro-developmental disorder is a uniquely human condition. Animal models are not the perfect tools for the full understanding of human development and behavior, but they can be an important place to start. This review focused on the recent updates of animal model research in autism.MethodsWe have reviewed the publications over the last three decades, which are related to animal model study in autism.ResultsAnimal models are important because they allow researchers to study the underlying neurobiology in a way that is not possible in humans. Improving the availability of better animal models will help the field to increase the development of medicines that can relieve disabling symptoms. Results from the therapeutic approaches are encouraging remarkably, since some behavioral alterations could be reversed even when treatment was performed on adult mice. Finding an animal model system with similar behavioral tendencies as humans is thus vital for understanding the brain mechanisms, supporting social motivation and attention, and the manner in which these mechanisms break down in autism. The ongoing studies should therefore increase the understanding of the biological alterations associated with autism as well as the development of knowledge-based treatments therapy for those struggling with autism.ConclusionIn this review, we have presented recent advances in research based on animal models of autism, raising hope for understanding the disease biology for potential therapeutic intervention to improve the quality of life of autism individuals.

scholarly journals Discovery Methodology of Novel Conotoxins from Conus Species

Marine Drugs ◽  
2018 ◽  
Vol 16 (11) ◽  
pp. 417 ◽  
Author(s):  
Ying Fu ◽  
Cheng Li ◽  
Shuai Dong ◽  
Yong Wu ◽  
Dongting Zhangsun ◽  
...  
Keyword(s):  
Drug Development ◽  
Gene Cloning ◽  
High Throughput ◽  
Disulfide Bond ◽  
Cone Snail ◽  
Crude Venom ◽  
Drug Candidates ◽  
Conus Species ◽  
New Drug Development ◽  
Natural Peptides

Cone snail venoms provide an ideal resource for neuropharmacological tools and drug candidates discovery, which have become a research hotspot in neuroscience and new drug development. More than 1,000,000 natural peptides are produced by cone snails, but less than 0.1% of the estimated conotoxins has been characterized to date. Hence, the discovery of novel conotoxins from the huge conotoxin resources with high-throughput and sensitive methods becomes a crucial key for the conotoxin-based drug development. In this review, we introduce the discovery methodology of new conotoxins from various Conus species. It focuses on obtaining full N- to C-terminal sequences, regardless of disulfide bond connectivity through crude venom purification, conotoxin precusor gene cloning, venom duct transcriptomics, venom proteomics and multi-omic methods. The protocols, advantages, disadvantages, and developments of different approaches during the last decade are summarized and the promising prospects are discussed as well.

scholarly journals Harnessing the medicinal properties of Cussonia barteri Seem. (Araliaceae) in drug development. A review

2018 ◽  
Vol 64 (3) ◽  
pp. 50-61 ◽  
Author(s):  
Ighodaro Igbe ◽  
Osaze Edosuyi ◽  
Agbonlahor Okhuarobo
Keyword(s):  
Drug Development ◽  
Antioxidant Activities ◽  
Biological Activities ◽  
Stem Bark ◽  
Deciduous Tree ◽  
Drug Candidates ◽  
Medicinal Properties ◽  
Phytochemical Constituents ◽  
Anti Inflammatory ◽  
Novel Drug

Summary Cussonia barteri Seem (Araliaceae) is a deciduous tree growing in savannah of Africa. Ethnomedicinally, it is used in Africa as an analgesic, anti-malarial, anti-inflammatory, anti-anaemic, anti-diarhoea, anti-poison, ani-pyschotic and anti-epileptic agent. This review provides a brief summary on the phytochemical screenings, ethnomedicinal and pharmacological applications of various parts of C. barteri. Leaves, stem bark and seed of C. barteri have been shown to be rich in saponins, flavonoids, phenols, sugars and alkaloids. Some of these constituents have been isolated and elucidated from C. barteri. Several compounds isolated from plant include triterpenes, saponins, polyenyne and quinic esters. Phytochemical constituents are also partly responsible for biological activities of C. barteri. Extracts and components isolated from the plant have demonstrated neuropharmacological, anti-larvicidal, anti-microbial, anti-inflammatory and antioxidant activities. Overall, the insights provided by this review reinforce the potential of C. barteri for drug development and create the need for further scientific probe of constituents of the plant with the aim of developing novel drug candidates.

Animal models of damage, repair, and plasticity in the brain

2015 ◽  
pp. 129-134
Author(s):  
Andreas Luft
Keyword(s):  
Animal Models ◽  
Human Condition ◽  
Functional Domain ◽  
Variable Degree ◽  
Social Emotional ◽  
Damage Repair ◽  
The Individual ◽  
New Treatments ◽  
The Brain ◽  
Multidimensional Process

Recovery after a stroke is a multidimensional process depending on the individual deficit. Within each functional domain, spontaneous recovery occurs to a variable degree and can be improved by specific neurorehabilitative interventions. The knowledge about the neurophysiology of the processes that lead to recovery and render neurorehabilitative interventions effective is scarce. Such knowledge, however, would be necessary to find new treatments that can fully exploit the brain’s capacity for recovery. Animal models can be an experimental platform to investigate these mechanisms. But it has to be realized that they oversimplify the human condition. The complexity of motor, cognitive, social, emotional, and other factors contributing to recovery in humans cannot be modelled in animals. The opportunities and caveats of animal models are discussed.

scholarly journals Correction: A standardised framework to identify optimal animal models for efficacy assessment in drug development

PLoS ONE ◽  
2019 ◽  
Vol 14 (7) ◽  
pp. e0220325 ◽  
Author(s):  
Guilherme S. Ferreira ◽  
Désirée H. Veening-Griffioen ◽  
Wouter P. C. Boon ◽  
Ellen H. M. Moors ◽  
Christine C. Gispen-de Wied ◽  
...  
Keyword(s):  
Animal Models ◽  
Drug Development ◽  
Efficacy Assessment

The Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC) protocol: novel method for evaluating human stroke

2018 ◽  
Vol 11 (3) ◽  
pp. 265-270 ◽  
Author(s):  
Justin F Fraser ◽  
Lisa A Collier ◽  
Amy A Gorman ◽  
Sarah R Martha ◽  
Kathleen E Salmeron ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Animal Models ◽  
Mechanical Thrombectomy ◽  
Tissue Banking ◽  
Human Condition ◽  
Molecular Response ◽  
High Quality ◽  
Link Type ◽  
Arterial Blood ◽  
First Time

BackgroundIschemic stroke research faces difficulties in translating pathology between animal models and human patients to develop treatments. Mechanical thrombectomy, for the first time, offers a momentary window into the changes occurring in ischemia. We developed a tissue banking protocol to capture intracranial thrombi and the blood immediately proximal and distal to it.ObjectiveTo develop and share a reproducible protocol to bank these specimens for future analysis.MethodsWe established a protocol approved by the institutional review board for tissue processing during thrombectomy (www.clinicaltrials.govNCT03153683). The protocol was a joint clinical/basic science effort among multiple laboratories and the NeuroInterventional Radiology service line. We constructed a workspace in the angiography suite, and developed a step-by-step process for specimen retrieval and processing.ResultsOur protocol successfully yielded samples for analysis in all but one case. In our preliminary dataset, the process produced adequate amounts of tissue from distal blood, proximal blood, and thrombi for gene expression and proteomics analyses. We describe the tissue banking protocol, and highlight training protocols and mechanics of on-call research staffing. In addition, preliminary integrity analyses demonstrated high-quality yields for RNA and protein.ConclusionsWe have developed a novel tissue banking protocol using mechanical thrombectomy to capture thrombus along with arterial blood proximal and distal to it. The protocol provides high-quality specimens, facilitating analysis of the initial molecular response to ischemic stroke in the human condition for the first time. This approach will permit reverse translation to animal models for treatment development.

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