Reverse Translation for Assessment of Confidence in Animal Models of Multiple Sclerosis for Drug Discovery
We believe that moving away from animal disease models will not be the solution, as most diseases are too complex for in vitro modeling. Moreover, pathological processes in vulnerable tissues, such as the human brain, cannot be directly examined in patients. A wiser approach may be to invest in the improvement of the predictive validity (see Box 1) of animal models by a critical analysis of the reasons why forward translation (see Box 1) of promising therapies from the animal model to the clinic failed (Figure1). We posit here that because of their close proximity to humans, disease models in nonhuman primates (NHPs) are especially useful in such a reverse translation (see Box 1) strategy, as the drug that failed in the clinic can be retested in the animal model. We will use examples from our own research, autoimmune‐mediated inflammatory disease (AIMID), to illustrate how important information gained from reverse translation analysis of failed and successful treatments can guide the improvement of an NHP model for MS.