Genetox Screening Assays Provide Practical Link Between Drug Discovery and Development

Continuing improvements in our understanding of molecular mechanisms of disease, when considered with the aging of the population, have created both new opportunities for drug discovery and a potentially huge market for newly developed pharmaceuticals.

In consideration of the large number of new molecules being generated in pharmaceutical, biotechnology, and university laboratories, and the immense costs of drug development, prioritization of drug candidates is necessary to direct resources to those new molecules that offer the greatest probability of improving human health.

In addition to studies of agent efficacy and general toxicity, genetic toxicity testing is a key element of non-clinical drug development. Although genetic toxicology testing is generally the least expensive battery of IND-enabling non-clinical toxicology tests, its costs are still substantial, notes Dr. Patrick Curry, Senior Genetic Toxicologist in IITRI's Microbiology and Molecular Biology Division.

The use of genetic toxicology screening assays can greatly reduce that expense. For a fraction of the cost of a complete genetic toxicology test battery, these "miniature" gene-tox studies can identify agents whose genetic effects may preclude further development.

	"We designed the screening study to use a minimum of test article to get the maximum information in the shortest amount of time." Dr. Patrick Curry Senior Genetic Toxicologist

"Screening up front, before formal GLP genetox testing, allows 'problem' compounds to be eliminated at the discovery/development interface. This results in more efficient selection of lead compounds and better allocation of resources," Curry says. Using this approach, "genetox screening assays are the practical link between drug discovery and drug development."

Minimal Investments Yield Valuable Results

Dr. Curry, who holds a Ph.D. in Zoology and Physiology from the University of Wyoming, was among the scientists who refined genetic toxicology screening assays in the years following their inception in the mid- 1980s. "We designed the screening study to use a minimum of test article to obtain the maximum information in the shortest amount of time," says Dr. Curry, author of 18 articles and 20 abstracts in the field of genetic toxicology.

The screening assay answers one basic question: Does the test article pose a risk of genetic damage? If screening assay data suggest that the answer is yes, the developer can eliminate that compound from further consideration, having made only a minimal investment in its development. If the screening reveals no risk of genetic toxicity, the compound may warrant further study.

Pharmaceuticals Are Primary Candidates

Although genetox screening assays can be used in the testing of any chemical compound, the demand for quick, cost-effective screening is especially high in the pharmaceutical industry. The application of library screening strategies, functional genomics, and proteomics to drug development promises to yield large increases in the number of new agents that offer potentially useful biological activity.

With the aging of the population, disease targets such as hypertension, diabetes, cardiovascular disease, and Alzheimer's disease offer compelling targets for new drug development. In addition, pathogenic bacteria continue to evolve to resistant states, thereby diminishing the efficacy of existing antibiotics and creating a need for new ones.

Genetic toxicology screening and other strategies that enable pharmaceutical companies to optimize their investment in drug development offer a clear win-win situation. The prospect of identifying effective agents quickly and inexpensively translates into new useful drugs for consumers and increased revenues for their developers.