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The Current issue of “The view from here” is concerned with Models

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The excitement of the Football World Cup is now over and we are well into the holiday season. This might be the silly season for the newspaper industry, but we get no such break in the white heat of Drug Discovery as covered by Drug Discovery Today. This month’s offering covers a very diverse field – that of models. We are all familiar with the use of models in our industry, but as with many concepts everybody’s concept differs. That is reflected in our offering this month and I hope you agree that we cover a wide range of “models” ranging from development using modern gene editing tools, to cutting edge in vitro models and animal models that have all shown themselves to be essential in advancing drug development.

 

The first article in this month’s offering is entitled: “Use of CRISPR/Cas9 gene-editing tools for developing models in drug discovery”, by Gulzar Ahmad and Mansoor Amiji of The Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston,  USA. In this article, the authors provide insights into how the incredibly powerful editing tool, CRISPR/Cas9, can be used to create in vitro and in vivo models for the drug discovery industry capable of enhancing speed and capacity. The impact of the use of this technique has the real potential of accelerating the identification and validation of high value targets, essential for the move into precision medicine in the future.

 

The second article in the series moves away from the molecular biological arena, to the cell biology world. In particular it highlights a field that is becoming ever more influential, especially in (but not exclusive to) the field of oncology. It is by Miryam Mebarki, Annelise Bennaceur and Laurence Bonhomme-Faivre of the APHP-Hopital Paul Brousse Université, Paris, France and is entitled: “Human cell derived organoids as a new ex vivo model for drug assays in oncology”. It is not many years since the mainstay of screening for compounds for oncology were 2D culture models. I don’t have the space (or time) in this newsletter editorial to debate the pros and cons of 2D versus 3D drug screens, but it is fair to say that in general the more physiologically-relevant the culture system the more likely the hits from it will be relevant to the treatment of the disease in in vivo models. Some of the most exciting developments in compound screening in the past few years has been the practical development of what is essentially an ex vivo model system consisting of a 3D culture of stem cells to produce “organoids” – structures that are effectively phenotypic, replicates of the intended target organ. The article describes the development of the technique, in particular its applications in oncology and indicates the scope and limitations of the approach in preclinical studies.

 

Last, but by no means least, we feature the article by Henrik H. Hansen, Michael Feigh, Sanne S. Veidal, Kristoffer T. Rigbolt, Niels Vrang and Keld Fosgerau of Gubra Aps, Denmark  entitled: “Mouse models of nonalcoholic steatohepatitis in preclinical drug development” In contrast with the other two articles, this one covers a field that is very familiar to everyone within the pharmaceutical industry, which is the in vivo animal model. Although for ethical and economic reasons, there has been pressure to reduce animal usage and to reduce our reliance on animal models, they have endured as the best extrapolation from in vitro to human disease. Whether this will change in the future remains the subject of much debate, it is unlikely that animal models will disappear from the drug discovery project map in the near future, if ever. This particular article deals with mouse models of a disease that is becoming more and more prominent in the Western world, such that it is now the major cause of chronic liver disease. The authors discuss the possible causes and pathogenesis of the disease and those strategies that have been adopted to find agents that may interfere with the process. They go on to describe in some detail the models that have been used to investigate drugs that may prove effective and the current status of trials of compounds intended to treat this disease.

 

 

Steve Carney was born in Liverpool, England and studied Biochemistry at Liverpool University, obtaining a BSc.(Hons) and then read for a PhD on the Biochemistry and Pathology of Connective Tissue Diseases in Manchester University, in the Departments of Medical Biochemistry and Histopathology. On completion of his PhD he moved to the Kennedy Institute of Rheumatology, London, where he worked with Professor Helen Muir FRS and Professor Tim Hardingham, on the biochemistry of experimental Osteoarthritis. He joined Eli Lilly and Co. and held a number of positions in Biology R&D, initially in the Connective Tissue Department, but latterly in the Neuroscience Department. He left Lilly to take up his present position as Managing Editor, Drug Discovery Today, at Elsevier. Currently, he also holds an honorary lectureship in Drug Discovery at the University of Surrey, UK. He has authored over 50 articles in peer-reviewed journals, written several book chapters and has held a number of patents. In the last month, Dr. Carney has extended his television and film portfolio by appearing in the Disney film “Christopher Robin”, a natural progression of his in-demand tenor horn skills that have in the past been seen on national TV in the UK (BBC, ITV, channel 4) and France (France 2) and in TV movies such as Harry Price: Ghost Hunter. Other major developments are in the pipeline, so please watch here for developments.

 

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