In vitro and in vivo pharmacological models to assess demyelination and remyelination.
In making a selection of cellular tools and animal models for generating screening assays in the search for new drugs, one needs to take into consideration the practicality of their use in the drug discovery process. Conducting high-throughput primary screens using libraries of small molecules, close to 1 million members in size, requires the generation of large numbers of cells which are easily acquired, reliably enriched, and reproducibly responsive to standard positive controls. These cells need to be similar in form and function to their counterparts in human disease. In vitro assays that can be mechanized by using robots can therefore save time and costs. In selecting in vivo models, consideration must be given to the species and strain of animal chosen, the appropriateness of the model to human disease, the extent of animal husbandry required during the in-life pharmacological assessment, the technical aspects of generating the model and harvesting the tissues for analyses, the cost of research tools in terms of time and money (demyelinating and remyelinating agents, amount of compound to be generated), and the length of time required for drug testing in the model. A consideration of the translational aspects of the in vivo model compared to those used in the clinic is also important. These themes will be developed with examples for drug discovery in the field of CNS demyelination and repair, specifically as it pertains to multiple sclerosis.
Merrill
Jean E
JE
CNS Division, Neurology Section, Sanofi-Aventis, Bridgewater, NJ 8807, USA. jean.merrill@sanofi-aventis.com
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy
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