Well, by the time this article is sent out we will know the winners of the 2018 World Cup. I do now know that it won’t be England, which gives me the opportunity more fully to concentrate on the more important (some would say) business of drug discovery. Easy to say that when you have lost, I suppose. In any case, the theme for this month’s newsletter offering is “Novel Targets” and selecting articles for this represents just as difficult a prospect as that of naming the winner of the World Cup, although I might point out that none of the articles in this mailing are from either Croatia nor France, in strict adherence with the Drug Discovery Today policy of impartiality. Selecting articles to highlight the topic of Novel Targets is difficult in that they need to be sufficiently early stage to represent good areas for research for drugs for unmet clinical need, yet sufficiently mature that they have a good likelihood of success, with respect to the ability to modify pathological processes with good druggability as viewed from PK/ PD or medicinal chemistry perspective. As in sport, everyone has their own view on “Novel Targets” and I hope that you agree with my choices or, at least, that it sparks some comment or discussion.  

The first article in this month’s offering is entitled: “Molecular epigenetic targets for liver diseases: current challenges and future prospects”, by Robert Zeidler, Bruno Leonardo de Freitas Soares, Augustinus Bader and Shibashish Giri of Leipzig and Munich, Germany. In this article, the authors highlight, not a single target, but a potential group of novel targets for liver diseases that derive from epigenetic approaches. The article demonstrates how epigenetics can inevitably represent excellent leads for the treatment of liver diseases, not least hepatocellular carcinoma. The advantages of modifying gene expression without changing DNA sequence or blocking are highlighted in the review. Clearly, modulation of the epigenome may represent a great step forward for the treatment of liver diseases that currently represent a massive unmet clinical need. 

The second article in the series deals with approaches to the treatment of a disease that affects a very different population than the first. It is by Vineet Jain and Keerti Jain of the Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Raebareli, India  and is entitled: “Molecular targets and pathways for the treatment of visceral leishmaniasis”. Currently, the treatment of leishmaniasis is hampered by the development of resistance to current “gold standard” first line drugs (and their inherent toxicity). Also, in many and other approaches are not available. For example, a clinically-approved vaccine for the disease is not yet available. Moreover, as this disease is most prominent in underdeveloped and developing countries, cost is a major factor as is the availability of suitable infrastructure to support, for example, a vaccine-led approach. This article deals with the approach to molecular targets within the parasite itself that may represent useful approaches to the treatment of this serious tropical disease.

And finally, we highlight an article from Vanessa Abella, Jesús Pino, Morena Scotece, Javier Conde, Francisca Lago, Miguel Angel Gonzalez-Gay, Antonio Mera, Rodolfo Gómez, Ali Mobasheri and Oreste Gualillo entitled: “Progranulin as a biomarker and potential therapeutic agent” In contrast with the previous article the identification of progranulin as a potential target addresses diseases that are firmly ensconced in the developed world. Progranulin has been established as being a major participant in inflammation and tumorigenesis since its initial discovery as an adipokine involved in diverse signaling processes impacting obesity, insulin resistance and rheumatic arthritides. The article gives a wonderful overview of the current scientific literature related to its validity as a therapeutic target. Should its potential be realized, then it is possible that drugs could be developed that could address fields as diverse as cancer, neurodegenerative disease and rheumatology.

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.