The Current issue of “The view from here” is concerned with Drug Repurposing.

The topic of this month’s newsletter from Drug Discovery Today is “Drug Repurposing”.

As the Pharmaceutical industry continues to change and methods of identification and stratification of disease becomes even more precise as the genetic basis of many disorders becomes clear, approaches become available to the industry that in the past may have not seemed so attractive or profitable. As the Blockbuster approach to drug development looks increasingly unlikely to be achieved in future, companies have reviewed their opinions on drug repurposing. Drugs which could not achieve statistically significant in a mixed population can be highly effective in a stratified subdivision of a particular disease. The benefits for patients are obvious, especially for those suffering from diseases where there is an unmet clinical need, and also for industry in that they may be able to derive some benefit from a compound that had previously failed. There is another massive benefit, in that this is a potential route for the development of drugs for diseases that might not otherwise attract much attention from Pharma – such as parasitic disease, as outlined in the article by Leonardo G. Ferreira and Adriano D. Andricopulo. I hope you enjoy this month’s offerings and that it may make you think that you may be able to adopt similar processes in your particular therapeutic area.

The first article in this month’s offering from the start of the year is entitled:” Defining drug response for stratified medicine”, by Mike Lonergan, Stephen J. Senn, Christine McNamee, Ann K. Daly, Robert Sutton, Andrew Hattersley, Ewan Pearson and Munir Pirmohamed. I guess this article isn’t specifically targeted at drug repurposing, however, as the genetic basis of disease becomes evermore well-understood, the prospects of reutilizing drugs that may have failed (or shown only marginal efficacy) in clinical trials for a particular disease in a well-defined population becomes highly attractive. The salvage of drugs is also a potential way that one may be able to obtain compounds to treat disease where the ROI may be marginal to set up a de novo full-blown drug discovery programme.

The second featured article is by Quentin Vanhaelen, Polina Mamoshina, Alexander M. Aliper, Artem Artemov, Ksenia Lezhnina, Ivan Ozerov, Ivan Labat and Alex Zhavoronkov of Insilico Medicine Inc., Johns Hopkins University and BioTime Inc., Alameda, CA USA l and is entitled: “Design of efficient computational workflows for in silico drug repurposing”. This is a much more directed article, involved with in silico approaches to the identification of potential alternative uses for drugs. The article is a much more applied approach, outlining a generic, modular approach for such computational studies. The manuscript provides a comprehensive overview of current computational strategies with respect to computational drug repurposing.

Next, from Wei Sun, Philip E. Sanderson and Wei Zheng, of the National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA comes a short review entitled: “Drug combination therapy increases successful drug repositioning”. They describe an interesting hypothesis in which they suggest that, although there is ever-increasing interest in drug repurposing, many newly-identified compounds have low efficacy and cannot achieve clinically-relevant plasma concentrations. The authors suggest an approach to overcome this, through the use of a second pharmacologically-different compound modifying another relevant, but different, part of the disease mechanism. Such combinations may produce useful effects and improve the rate of successful repositioning of otherwise unused drugs.

Finally, is the article “Drug repositioning approaches to parasitic diseases: a medicinal chemistry perspective” from Leonardo G. Ferreira and Adriano D. Andricopulo from the Laboratório de Química Medicinal e Computacional, Universidade de São Paulo, Brazil. This is a more applied article, which identifies and highlights how useful therapies for neglected tropical diseases can be developed in this manner. They go on to describe how the association of not-for-profit organisations, academia and industry can enable useful repurposing screening approaches. The authors point out how similar approaches have led to benefit in patients suffering from such conditions and how important current studies will be in identifying drugs for preeminent parasitic disorders.  

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.

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