Limitation of Animal Models

The following issues are not always appreciated in drug discovery and can contribute to the high attrition rate in clinical development.

For a full report see Geerts 2009 "Of Mice and Men: Bridging the translational disconnect in CNS R&D".

Parameter
Animal models ISB Computational Platform
Drug Affinities Clinical candidate is often optimized for rodent target subtypes Accounts for possible differences because use of human target affinities
Neurotransmitter Circuits Differently wiring (receptor distributions) in rodents can limit predictivity Uses human circuits & distributions
Drug Exposure Rodents metabolize faster and different active metabolites can be formed Can use exposure and unique meatbolites from human patients
Functional Genotypes Specific human genotypes often impossible to recreate in rodent models Where imaging information available is incorporated into platform
Polypharmacy Very expensive and difficult to perform in preclinical models Approved psycho-active medications (antidepressants, anti-convulsants, sleep-medication and antipsychotics) part of the platform.
Complete Human Pathology Difficult to get complete pathology in rodent model Uses complete pathology from imaging and postmortem studies

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