Fail-Early Drug Screens
One of the most difficult problems facing pharmaceutical development is the need to discard drug candidates that have chronic side-effects early in the developmental process. Failure to do so can lead to significant adverse outcomes for both patients and pharmaceutical companies, including misallocations of resources by the pharmaceutical company (i.e. failure of a drug in expensive Phase III clinical trials) and eventual lawsuits by patients who have suffered major afflictions as a result of chronic side-effects.
Genescient has been concerned about this problem from the outset. Dealing with it has been built into our R&D strategies and platforms.
With strong genomic connections between model organism(s) and patient outcomes, it is appropriate to use model organisms to test for chronic side-effects. And that is a key step for our own R&D and a service that we can supply to other corporations.
At present, our chief model organism is Drosophila, the common laboratory fruit fly. With Drosophila, unlike all other available model organisms, we have the following attributes combined:
- Well-differentiated organ systems
- Males and females, with functioning gonads and complex reproductive behavior and physiology
- Hearts and blood circulation that typically weaken with age, as is the case with humans
- Distinguishable and integrated nervous systems
- Lifespans that are short enough to allow complete lifespan assays for side-effects on both mortality and fertility
- Complex behavior patterns that allow us to readily detective neurological impairment
Genescient has recently published a paper illustrating how we employ just some of the advantages of the Drosophila system for identifying chronic side-effects. See: Matsagas K, Lim DB, Horwitz M, Rizza CL, Mueller LD, et al. 2009. Long-Term Functional Side-Effects of Stimulants and Sedatives in Drosophila melanogaster. PLoS ONE 4(8): e6578. doi:10.1371/journal.pone.0006578