Fallacies of Mice Experiments
- PDF / 197,329 Bytes
- 3 Pages / 595.276 x 790.866 pts Page_size
- 31 Downloads / 227 Views
EDITORIAL
Fallacies of Mice Experiments Erik De Schutter 1 Published online: 2 April 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019
Recently, one of my PhD students complained that while presenting her poster, the scientific relevance of her modeling work was questioned aggressively by an experimentalist. So even at the end of the second decade of this millennium, theoreticians still have to justify the relevance of their work towards understanding the brain.1 In this editorial I want to demonstrate that, unfortunately, such high standards are not always applied to experimental work, in particular in mice. A first example is the recent news that two major Phase II trials for Alzheimer drugs have been canceled.2 These trials of humanized anti-amyloid-β monoclonal antibodies were based on the convergence of two sets of data: genetic risk for Alzheimer disease in humans indicating the importance of amyloid metabolism and extensive studies in transgenic mice.3 Many studies have shown that transgenic mice expressing gene mutations associated with human familial Alzheimer disease progressively develop brain amyloid plaques and memory deficits.4 Immunization against amyloid-β peptide rapidly reversed memory defects in some transgenic models 3,5 leading to the subsequent clinical trials. In hindsight, is the failure of such treatments in patients surprising? There were 1 De Schutter, E. (2008). Reviewing multi-disciplinary papers: a challenge in neuroscience? Neuroinformatics, 6(4), 253–255. https://doi.org/10.1007/ s12021-008-9034-x. 2
https://www.biospace.com/article/a-long-line-of-failures-roche-dropsalzheimer-s-drug-trials/
3
Panza, F., Lozupone, M., Logroscino, G., & Imbimbo, B. P. (2019). A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease. Nature Reviews Neurology, 1–16. https://doi.org/10.1038/s41582-018-0116-6. 4
Karran, E., Mercken, M., & De Strooper, B. (2011). The amyloid cascade hypothesis for Alzheimer’s disease: an appraisal for the development of therapeutics. 1–15. https://doi.org/10.1038/nrd3505. 5
Dodart, J.-C., Bales, K. R., Gannon, K. S., Greene, S. J., DeMattos, R. B., Mathis, C., et al. (2002). Immunization reverses memory deficits without reducing brain Aβ burden in Alzheimer’s disease model. Nature Neuroscience, 5(5), 452–457. https://doi.org/10.1073/pnas.94.4.1550.
* Erik De Schutter [email protected] 1
Computational Neuroscience Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan
already papers suggesting that the antibodies did not work in all mouse models of Alzheimer disease; noticeably these papers were published in lower impact journals.6 But I want to argue that, in general, mouse models are not very predictive of human disease. This conjecture is based on a preceding sequence of failures with drugs derived from mouse and other animal studies: those used for the treatment of septic shock. Of the 69 clinical studies performed in 1982–2013 that were analyzed in,7 only 8 resulted in some benefits and 4 actu
Data Loading...
