CNS Drugs

, Volume 23, Issue 11, pp 915–926 | Cite as

Of Mice and Men

Bridging the Translational Disconnect in CNS Drug Discovery
  • Hugo GeertsEmail author
Current Opinion


The tremendous advances in transgene animal technology, especially in the area of Alzheimer’s disease, have not resulted in a significantly better success rate for drugs entering clinical development. Despite substantial increases in research and development budgets, the number of approved drugs in general has not increased, leading to the so-called innovation gap. While animal models have been very useful in documenting the possible pathological mechanisms in many CNS diseases, they are not very predictive in the area of drug development.

This paper reports on a number of under-appreciated fundamental differences between animal models and human patients in the context of drug discovery with special emphasis on Alzheimer’s disease and schizophrenia, such as different affinities of the same drug for human versus rodent target subtypes and the absence of many functional genotypes in animal models. I also offer a number of possible solutions to bridge the translational disconnect and improve the predictability of preclinical models, such as more emphasis on good-quality translational studies, more pre-competitive information sharing and the embracing of multi-target pharmacology strategies.

Re-engineering the process for drug discovery and development, in a similar way to other more successful industries, is another possible but disrupting solution to the growing innovation gap. This includes the development of hybrid computational models, based upon documented preclinical physiology and pharmacology, but populated and validated with clinical data from actual patients.


Schizophrenia Preclinical Animal Model Amfetamine ApoE4 Gene Polymorphism Phenserine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Discussions with scientists at the Center for Neurodegenerative Disease (CNDR) laboratory at the University of Pennsylvania, in particular Kurt Brunden, Virginia Lee and John Trojanowski, are very much appreciated. The author is an employee of In Silico Biosciences, Inc., has acted as a consultant for the M. Ware Foundation, CNDR, University of Pennsylvania, and has received honoraria from Janssen Pharmaceutica. He is co-inventor and has a patent pending on mechanistic disease modelling in CNS disorders.


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Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  1. 1.In Silico Biosciences Inc.BerwynUSA

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