Wednesday, February 18, 2009

What is translational Pharmacology?

Rather than going through the well worked phrases of science that goes ‘from bench to bedside’ or from ‘mouse to man’, a more accurate definition might be ‘the application of biomedical research (pre-clinical and clinical), conducted to support drug development, which aids in the identification of the appropriate patient for treatment (patient selection), the correct dose and schedule to be tested in the clinic (dosing regimen) and the best disease in which to test a potential agent (disease segment)’. A challenge to say, let alone do, but it is fast becoming one of the most exciting research areas for pharmacologists to work in, as they get to see the translation of their hypotheses into the clinic for testing. 

Translational pharmacology (TP) can answer some simple questions once a drug candidate has emerged from a screening cascade. These include: 
• What disease might this agent work in? By testing in a number of pre-clinical models of human disease and working out whether this is predictive of disease in man some direction can be provided pre-clinically. 
• What dosing schedule can we test in the clinic for maximum therapeutic benefit with minimum toxicity, based upon the scientific profile of the molecule and data from pre-clinical models? 
• Can we use pharmacodynamic ‘biomarker(s)’ (measures of biological effect in man) to determine whether the compound blocks or stimulates the target receptor or enzyme in man as it does in animals (commonly known as proof of mechanism)? What effect does modulating the target have on the cellular phenotype that we might be trying to modulate (known as proof of principle, or proof of biology)? Does induction of this phenotypic change result in therapeutic benefit to the patient, and at what dose does this occur in the patients (proof of concept)? 
• Can we identify patients from within a disease population who might benefit from the agent, either by a gene mutational change or an over/under-expression of the protein target receptor or enzyme as examples? 
• If an agent is being developed as second or third in the market place (usually termed a ‘best in class’ agent), what differentiating pharmacology might this compound require in order to encourage regulatory agencies, physicians, and patients to test it? 
  Frankly speaking, TP is only a journey, not a specific scientific technique.
source: Netrum

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