Given the rationale behind the Journal, Drug Discovery Today, selecting the content for a monthly newsletter entitled Therapeutics should, on the face of it, be a piece of cake. I can assure you that this is not, in fact, the case. I looked through the recent issues of Drug Discovery Today and found that we were embarrassed with a cornucopia of riches with respect to this topic. So rather than have to search around for articles, I had to think what articles would be of greatest value to drug discovery professionals the world over. You may (perhaps probably will) disagree with my choice, but I would propose that one of the benefits of being an Editor is the ability to behave like a benign dictator in this respect. So, I based my selection on interesting articles that dealt with therapies for a very difficult to treat condition; one with significant impact in developing nations and one that dealt with treatments for immune disorders. All have a great unmet medical need and, I would propose, this is one of the key initiatives that should be addressed in any drug discovery project.
The first article addresses the efforts that have been expended in treating a devastating condition. It is entitled “Therapy for glioblastoma: is it working?” by Edward D. Zanders, Fredrik Svensson and David S. Bailey of IOTA Pharmaceuticals, Cambridge, UK. The authors highlight how glioblastoma is one of the most difficult cancers to treat and patients on average only survive 15 months following diagnosis. Clearly this represents a significant unmet clinical need, yet drug therapies remain somewhat ineffective. The authors propose that this may be, at least in part, as a result of significant heterogeneity and plasticity of the stem cell lineages that give rise to the tumour. They review the most recent clinical trial data for compounds in development and highlight that immunotherapeutic approaches to the ablation of the tumour would appear to represent the most effective approaches to date.
Following on from this is an article that highlights Rafael Balaña-Fouce M., Yolanda Pérez Pertejo, Bárbara Domínguez-Asenjo, Camino Gutiérrez-Corbo and Rosa M. Reguera of Departamento de Ciencias Biomédicas, Universidad de León, Spain entitled: “Walking a tightrope: drug discovery in visceral leishmaniasis”. Within this manuscript the authors point out that there is a current intention of a number of players, be it Pharma, NGOs and academic groups to address the issues of neglected tropical disease. These efforts have been manifest in the improved treatments though drug combinations and/or formulation. The article points out that the most significant tool in the advancement of novel drugs and drug combinations has been the introduction of phenotypic screening. Unfortunately, the hit rate from such approaches currently lags behind that expected from comparable approaches in other diseases. They highlight that there still is a need to develop new screening paradigms based upon the host immune system and its ability to fight such a devastating parasitic infection.
The final article this month “Small-molecule inhibitors of macrophage migration inhibitory factor (MIF) as an emerging class of therapeutics for immune disorders” comes from the pen of Tjie Kok, Anna A. Wasiel, Robbert H. Cool, Barbro N. Melgert, Gerrit J. Poelarends and Frank J. Dekker of Groningen, Netherlands. The article provides an interpharmacopoeial comparison of quality specifications of peptide-based drug monographs and areas for improvement in peptide therapeutics. The authors point out that MIF is a key player in the pathogenesis of both inflammatory diseases and cancer. It is an important cytokine with an ever-expanding portfolio of biological function. There is, however, a paucity of potent drug-like inhibitors of the molecule that have been characterized in animal models. This clearly represents a problem with progressing potentially useful molecules into the clinic to fight these very significant classes of 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.