The National Academies of Sciences recently published the proceedings of a workshop which addressed the ways in which drug development for nervous system disorders, such as Parkinson’s disease and Alzheimer’s disease, can advance “in the absence of animal models that reflect disease and predict efficacy.” Given that therapeutics developed for central nervous system disorders have the highest failure rate, and leading pharmaceutical companies are therefore retracting their investment in this area of study, the scientific community convened to discuss strategies for advancing the field.
Stevin Zorn, president and chief executive officer at MindImmune Therapeutics, stated that there are not currently, and there may never be, predictive animal models of complicated human diseases such as nervous system disorders. Why? There are many reasons.
Due to inherent differences between humans and animals, existing animal models may not produce the hallmark features or symptoms of disease. Animals are often genetically modified to express human genes associated with disease, but that doesn’t guarantee they will make good models. Sometimes, the genetic alterations may have minor consequences; other times, however, the consequences may be more dramatic. This may, in turn, complicate interpretation. Researchers must also recognize that the genetic background of animals is different from that of humans, which can make interpretation of the effects seen in animals challenging.
Steven Hyman, Chair of the planning committee for the workshop, indicated there is a “certain amount of sober realism” about how well central nervous system models translate to humans. He remains optimistic, however, because rather than “hanging on to the old way of doing things, people are thinking creatively about how to go forward.”
Experts in the field seem to agree that using human-relevant, innovative modeling approaches—including cell and computer models—as well as efforts to better utilize data coming from human clinical studies, are the right approaches.
Simply put, animal models fail to mimic the diseases they were meant to model. As a result, they may actually be screening out drugs that would have been effective in people, thereby keeping us from developing the very treatments and cures these models are meant to be facilitating.
“Therapeutic Development in the Absence of Predictive Animal Models of Nervous System Disorders: Proceedings of a Workshop,” The National Academies Press, March 2017