The Current issue of “The view from here” discusses translational medicine.

The topic of this month’s newsletter from Drug Discovery Today is translational medicine.

It goes without saying that drug discovery is a risky business. It is clear however that “the road to hell is paved with good intention”, how many of what seem like the best ideas in the laboratory do not make it to drugs, let alone successful drugs. It is clear that the hand over from an effective laboratory drug to clinical development is a crucial phase, where many brilliant ideas are lost. To some extent, in the past, the attrition at this phase was to some extent due to the fact that pre-clinical and clinical parts of an organization behaved as separate companies. This did not always result in smooth dovetailing of the process of transfer from one to another. It would be unfair also to blame the demise of compounds around this stage to the lack of coordination between the respective groups as many other factors come to bear. The transition of compounds from what is effectively an animal phase to a human phase is always problematic and may fail for a number of reasons, principally reflecting differences in animal and human physiology and the inadequacy of modelling the human condition in animal species. Adopting a more holistic approach around this transition period may help to ameliorate failure rates and hence improve the process overall.

The free downloads available in this newsletter highlight some of the most recent developments in translational research in drug discovery. I will elaborate on them below.

The first article, by C. Simone Fishburn of Exponent Inc., Menlo Park, CA 94025, United States, entitled “Translational research: the changing landscape of drug discovery”  describes the process and value of translational research. Moreover, they outline the translation cycle that drives improvements in the process. They define translational research as follows: “The hallmark of the translational approach to drug development is that it incorporates the target of a specific unmet clinical need from the outset. Unlike traditional research-based discovery, which seeks to understand basic cellular mechanisms and apply these learnings to design new therapies, translational research targets mechanisms underlying clinically relevant problems and designs drugs to address those issues directly. At its broadest, translational research encompasses three principal components: laboratory research, clinical practice, and population effects in the community. These are often described in a two-stage process, termed T1 and T2, which refer to laboratory-to-clinic and clinic to community stages, respectively”. 

The second article, an Editorial from Alan Palmer and Lars Sundstrom,  entitled: “Translational medicines research”, outlines how, in the past, there was a distinct divide between fundamental and applied research. Towards the end of the 20th century, these boundaries became more fuzzy and indistinct, typified by the suggestion of translational research and the “bench to bedside” approach, coined in and around 1968. The authors describe how the approach is now gaining in popularity and how it “It encompasses all research activity from fundamental biology to a marketed drug”. They point out that translational medicine represents a new model for drug development, based upon open and integrated partnerships and stakeholder involvement, improving the efficiency of the process and, hopefully, improving drug development.

 Finally, is the review from Alan M. Palmer and Mohammad S. Alavijeh of MS Therapeutics Ltd., Crowthorne, Berks UK and Pharmidex Pharmaceutical Services Ltd., London, UK respectively, entitled, “Translational CNS medicines research”.  Development of CNS drugs has its own particular problems, related to specific differences in the target organ, compared with other medicines. Such differences include a lack of specific understanding of the pathophysiology of particular CNS disorders, the variable quality of animal models of psychiatric disease, relative unpredictability of side effects and the passage of drugs across the blood-brain barrier. The review concentrates on the factors that are critical in driving neuroscience research into useful new psychiatric and neurologic products for treatment of disorders. This is particularly important as, on average, CNS drugs take longer to discover and develop and have a higher attrition rate than drugs for other diseases. Psychiatric drugs address an essential, important, relatively unmet clinical need and a major source of revenue for Pharmaceutical companies. Hence it is medically and commercially critical to ensure that translational research be optimized for this class of compounds.

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 40 peer-reviewed articles, written several book chapters and has held a number of patents.

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