Question

Which method is ususally used to measure the response of human tissue in the test for designing drug?

Answer 1

The high rate of failure during drug development is well-known, however recent advances in tissue engineering and microfabrication have contributed to the development of microphysiological systems (MPS), or ‘organs-on-chips’ that recapitulate the function of human organs. These ‘tissue chips’ could be utilized for drug screening and safety testing to potentially transform the early stages of the drug development process. They can also be used to model disease states, providing new tools for the understanding of disease mechanisms and pathologies, and assessing effectiveness of new therapies. In the future, they could be used to test new treatments and therapeutics in populations - via clinical trials-on-chips - and individuals, paving the way for precision medicine. Here we will discuss the wide-ranging and promising future of tissue chips, as well as challenges facing their development.

The drug development pipeline has well-documented high failure rates, and is expensive and time-consuming.When a drug reaches the clinical trials stage, the probability of clinical success is around only 12%. Once a biological target for a potential medicine is found, and a lead compound is identified, the pharmacokinetics (how the body processes the drug) and pharmacodynamics (what the drug does to body functions) must be profiled before the compound can be taken further to preclinical studies. At these stages, much of the testing is done in two-dimensional cell cultures and animal models. Two-dimensional cell culture tests can be extremely useful for fast, cheap and high-throughput testing of potentially toxic compounds, and animal testing gives important readouts of the organism-level effects in vivo. However, neither method adequately models human physiological responses. Human tissues are 3D in nature, and this structure and heterogeneous environment, from the presence of multiple cell types and cell-cell interactions.Animal models can miss important off-target effects or toxicities that would be manifested in humans, because of species differences in physiology and drug response. For example, genetic differences between species can lead to differences in drug target binding, metabolizing enzymes, and metabolites. Indeed, these species-specific differences may prove catastrophic if not realized early on – a small difference in CD28 receptor expression patterns between humans and monkeys caused multiple organ failure in phase 1 clinical trials of six human volunteers for the drug TGN1412, being developed for immune system disorder