Translational medicine

In addition to the discovery of fundamental medical science, additional research is needed to aid the transition of those discoveries toward the production of usable devices. As in any medical application, researchers must always consider the processes needed for clinical trials, whether the chosen vector is suitable for use in the body, and the potential for FDA approval and manufacturing scale-up.  

This work, termed translational medicine, is needed to address new nanoenabled products, such as following  

In parallel with developing convalescent sera or vaccines, it is important to develop advanced, rapid diagnostic devices that idenlily a specific threat agent. This basic information would be required for prevention, detection, diagnosis, and therapy. Near-term technologies should be aimed at providing partial information immediately followed by a thorough evaluation. 

Enabling infrastructure may also be leveraged as part of basic and translational research efforts for nanotechnology-enable medical countermeasures for CB defense. As an example, a family of animal models that support the evaluation of nanomaterials needs to be established and integrated into the approval process. 

Appropriate animal models need to be verified for nanomaterial flows, toxicity, pharmacokinetics, and immune response.  

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The ultimate model is the human in the clinical situation. Translational medicine with noninvasive imaging techniques and biomarkers is now able to furnish valuable information that can be used in the initial discovery process to produce better defined drugs. 

Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA... 

Work in the authors laboratory is supported by grants form the Medical Research Council (UK), the Wellcome Trust and the UK Multiple Sclerosis Society. S.M.A. is a MRC Senior Research Fellow and holds a RCUK Fellowship in Translational Medicine. 

Arce, C., Segura-Pacheco, B., Perez-Cardenas, E., Taja-Chayeb, L., Candelaria, M. and Duennas-Conzalez, A. (2006) Hydralazine target from blood vessels to the epigenome. Journal of Translational Medicine, 4, 10. 

Tal Zaks, MD, PhD Translational Medicine-Oncology, GlaxoSmithKline, Collegeville, Pennsylvania, USA... 

Zdolsek J, Eaton JW, Tang L. Histamine release and fibrinogen adsorption mediate acute inflammatory responses to biomaterial implants in humans. Journal of Translational Medicine 2007, 5, 31. 

Transitioning into an initial exploratory clinical evaluation rests upon safety and functional understanding built during preclinical evaluation. The preclinical program establishes assessment objectives related to specific product characteristics and the supporting production processes. Translational medicine study results define the extent to which preclinical information demonstrates... 

G. A. FitzGerald, Anticipating change in drug development The emerging era of translational medicine and therapeutics. Nature Rev. Drug Discovery 4 (2005), 815-818. 

The recommendation that, where appropriate, new animal models of human disease(s) be introduced into drug safety assessment should be an area of active research in translational medicine.32... 

Andrea D. Eckhart Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA... 

Ionannidis J. Materializing research promises Opportunities, priorities and conflicts in translational medicine. J Tanslational Med 2004 2 5. 

An added complexity, but one that may better predict therapeutic activity, is the testing of drugs in assays with different contexts (i.e., basal stimulation). Testing in vivo can further produce therapeutic model systems. Certain multicomponent disease conditions can be adequately modeled only in vivo. The ultimate model is the human in the clinical situation. Translational medicine with noninvasive imaging techniques and biomarkers now are able to furnish valuable information that can be used in the initial discovery process to produce better-defined drugs. 

Gough, D.A., Kumosa, L.S., Routh, T.L., Lin, J.T., and Lucisano, J.Y. (2010) Function of an implanted tissue glucose sensor for more than 1 year in animals. Science Translational Medicine, 2 (42), 42ra53. 

Perez OD, Nolan GP. Phospho-proteomic immune analysis by flow cytometry from mechanism to translational medicine at the single-cell level. Immunol Rev 2006 210 208-228. 

Figure 19.4 Examples of drugs that were derived from translational chemistry, translational research and translational medicine, respectively (1) d-tubocurarine (2) propranolol and (3) esmolol. Also shown is sildenafil, (4), which is probably best considered to have been derived from a composite of all three of these drug discovery starting points. See text for details.

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