Chunk #10 — Problems of Successful Translation to Humans of Data from Animal Experimentation — The Discordance between Human Diseases and Animal Models of Diseases
Further examples of repeated failures based on animal models include drug development in cancer, amyotrophic lateral sclerosis (ALS), traumatic brain injury (TBI), Alzheimer’s disease (AD), and inflammatory conditions. Animal cancer models in which tumors are artificially induced have been the basic translational model used to study key physiological and biochemical properties in cancer onset and propagation and to evaluate novel treatments. Nevertheless, significant limitations exist in the models’ ability to faithfully mirror the complex process of human carcinogenesis.27 These limitations are evidenced by the high (among the highest of any disease category) clinical failure rate of cancer drugs.28 Analyses of common mice ALS models demonstrate significant differences from human ALS.29 The inability of animal ALS models to predict beneficial effects in humans with ALS is recognized.30 More than twenty drugs have failed in clinical trials, and the only U.S. Food and Drug Administration (FDA)–approved drug to treat ALS is Riluzole, which shows notably marginal benefit on patient survival.31 Animal models have also been unable to reproduce the complexities of human TBI.32 In 2010, Maas et al. reported on 27 large
