Targeting disease, not disease targets: Innovative approaches in tackling neurodegenerative disorders.
Preclinical drug investigation entails identifying and optimizing drug candidates to yield effective therapeutics with an acceptable level of adverse side effects. Inevitably, this investigation phase is bound to using model systems that mimic crucial aspects of disease biology in order to assess drug efficacy. The quality or predictability of these disease models is therefore of utmost importance to the development of successful drugs. Models should also be cost-effective and, from a biological point of view, sufficiently simple to enable molecules that act specifically (ie, that modulate a single, pre-defined target) to be identified easily and to allow for HTS. To meet these demands, typical drug discovery approaches rely heavily on biochemical assays in which the activity of a pre-defined target is reconstituted artificially. However, such a rational reductionist approach may compromise the predictability of a model because targets are assessed in an artificial environment that is deprived of any relevant biological context. Moreover, given the pre-established limits on target space and mode of action in a model, efficient and innovative drug discovery programs may be hampered. This feature article considers alternative or complementary approaches that advocate the introduction of biological context early in the drug discovery process. A case study of how NV reMYND has implemented 'biology-driven' drug discovery is presented.
Griffioen
Gerard
G
NV reMYND, Gaston Geenslaan 1, B-3001 Leuven-Heverlee, Belgium. gerard.griffioen@remynd.be
D000818:Animals; D003198:Computer Simulation; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D040901:Proteomics