Indian Journal of Pharmacology Medknow Publications on behalf of Indian Pharmacological Society ISSN: 0253-7613 EISSN: 1998-3751 Vol. 43, Num. 2, 2011, pp. 103-104

Indian Journal of Pharmacology, Vol. 43, No. 2, March-April, 2011, pp. 103-104

Editorial

Promise of translational medicine: An evidence-based therapeutics

M.U.R Naidu

Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences, Panjagutta, Hyderabad, India

Correspondence Address: M.U.R Naidu, Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences, Panjagutta, Hyderabad, India, murnaidu@yahoo.com

Code Number: ph11033

DOI: 10.4103/0253-7613.77332

Translational medicine (TM) is often labeled as "Bench to Bed-side" since it involves the movement of research from laboratory to the clinical practice. TM is synonymous with "Molecular Medicine" or "Personalized Medicine" as all of them refer to the process of applying molecular insight to the clinical care of the patients. TM has a new paradigm and it differs from traditional drug discovery and development. As per the Journal of Translational Medicine, it is a bidirectional process, the first one goes from "bench to bed-side" where theories emerging from preclinical experiments are tested on disease-affected human subjects and then from "bed-side to bench," where information obtained from human experiments is used to refine the understanding of biological principles, heterogeneity of human disease, and polymorphism.

In recent years, significant change has come about our understanding of disease process due to the evolution of genomics and bioinformatics. TM as a branch of medical science attempts to connect basic research to patient care more directly. In drug discovery and development, TM typically refers to the translation of basic research into real therapies for real patients. Researchers are now engaged in a large-scale hunt for new biomarkers using new genomic and proteomic tools. The specific biomarkers are being carefully identified to answer the specific questions.

TM can be better understood in clinical practice if one looks to answer the following questions:

• Will there be variations in drug response due to pharmacogenetics, or will every patient respond similarly to a particular drug?
• What will be the optimum dose to obtain an adequate response?
• Is there proof that a particular drug is really changing the pathophysiology of the disease process?
• Which patient is likely to have an adverse effect? Can we identify such a patient population based on investigations?

Specific biomarkers like HER2/neu in breast cancer, EPGR mutations in non-small-cell lung cancer have been successfully used in clinical drug evaluations. PET imaging of biomarkers like reduction of amyloidal burden in Alzheimer′s disease, change in cytokine profile in inflammatory diseases, and change in glucose uptake by tumor cells are used to assess the early alterations of pathophysiology of diseases. Urotensin II system is unique and plays a role both in insulin secretion and the renal complication of diabetes. Thus, Urotensin II receptor antagonists are new promising agents for the therapeutic management of diabetes. Observation of prolongation of QT interval with drugs acts as an early indicator of cardiotoxicity. Similarly, gene studies pertaining to hemorrhagic or cerebral stroke, genetic profile of genes like G6PD, and study of cytochrome 450 variants would provide the pharmacogenetic basis of drug effect variations in patients. In a long run, application of pharmacogenetics in clinical practice will significantly contribute toward individualization of drug therapy, known as personalized medicine. Drug interaction studies which can be easily carried out in vitro and in vivo, and drug metabolism studies during preclinical drug development may also become a potential source for the discipline of TM.

TM is patient centered, thus, and is also referred sometimes as the development and application of new technology in a patient-driven environment where the emphasis is on early patient testing and evaluation. We are now observing more and more patient-driven research processes and more of research- and evidence-based clinical practice of medicine. With the application of TM, both clinical research and clinical trials have become more objective. Today, during the early stage of drug development, it is possible to study the effect of new therapeutic agents on gene expression in cell lines, and also possible to find out any adverse effect due to genotoxicity. Hence, the regulatory agencies are very much hopeful that TM would be a boon to establish a suitable risk/benefit profile of a drug in the early stages of drug development.

Thus, US-FDA declaration of a protocol of critical path research for the clinical development of drug is not surprising. Recently, US FDA described the concept of "critical path initiative" which states that "critical path research is directed towards improving the medical product, development process by establishing new evaluation tools together with academia, patient groups, industry and governmental agencies. We need to embark on an aggressive, collaborative research effort to create a new generation of performance standards and predictive tools that will provide better answers about the safety and effectiveness of investigational medicine faster and with more certainty." It is also possible to identify the promising molecules in early stage by practicing TM. Emergence of TM and pharmacogenetics as an area of clinical practice has raised the hope of individualization of drug therapy. Right medicine in right dose to a right patient.

Copyright 2011 - Indian Journal of Pharmacology