Drug researchers adopt 'in vivo' techniques
models to streamline pre-clinical drug development in an effort to
cut costs that are increasing steadily throughout the
pharmaceutical industry's drug pipeline.
The tightening of legislation by regulatory bodies and the decrease in R&D budgets means that research is increasingly being linked to the biology of the human system as closely as possible in the drug candidacy process.
With this, more and more drug companies are eagerly searching for ways to fill these pipeline voids and are now exploring new in vivo models to base their pre-clinical drug development.
"While established mammalian models have limited utility as drug discovery tools, some of the emerging in vivo models can be used for target and lead discovery and also enable early detection of drug toxicity," said Dr Randall Peterson, assistant professor of medicine, Massachusetts General Hospital and Harvard Medical School.
The comments were made as scientists and life science companies will gather for PharmaDiscovery 2005 on May 10-12, to tackle issues surrounding drug development including trends like emerging in vivo models.
The PharmaDiscovery Conference will allow scientists from both academia and industry to address key questions surrounding current models and the benefits of an in vivo approach in evaluating drug efficacy and safety," Peterson added.
Scientists working in today's drug discovery and development arena have a wide range of technologies to choose from to unravel biological mechanisms. However, the answers these technologies provide may be only as good as the physiological models to which they are applied.
An example of an in vivo tool in phenotype-based screens is the use of genome and body makeup of zebrafish, which are very similar to humans, making for ideal disease models.
The increasing number and diversity of compounds generated by rapid synthesis techniques, combined with high throughput in vitro assays, generate large number of preliminary 'hits'. However, validating these preliminary hits in animals is very slow and costly, resulting in a gap in drug discovery research. The zebrafish is a small vertebrate model organism that can bridge this gap.
Zebrafish-based assays combine the advantages of higher throughput analysis (compared to mammalian models) and higher relevance to humans (compared to in vitro models). Drug screening assays in diverse formats have been developed using zebrafish, including visual assessment of effects on organs in the transparent embryo and quantitative assays using microplates.
As a result, many leading scientists, and pharmaceutical companies, are adopting these new in vivo models for pre-clinical drug development that solve many problems of traditional in vitro models. However these models may not illustrate the complete picture of biological interactions, and traditional in vivo models that are expensive and difficult.
"The emergence of more unprecedented targets creates a bottleneck in lead optimisation as the industry attempts to define drug-like properties within lead series and solve mechanisms to toxicity. Adopting higher throughput systems biology approaches is essential to ease this block," said Dr James Stevens, research fellow, toxicology and drug disposition, Lilly Research Laboratories.
"Identifying mechanisms of drug action and toxicity linked to modulation of complex signalling pathway can only be determined from the examination of intact multicellular organisms. These new in vivo models represent a viable and higher throughput approach to optimising the efficacy and safety of drug candidates," he added.
