Therapeutic Trial of anle138b in Mouse Models of Genetic Prion Disease
Sonia M. Vallabh, Dan Zou, Rose Pitstick, Jill O’Moore, Janet Peters, Derek Silvius, Jasna Križ, Walker S. Jackson, George A. Carlson, Eric Vallabh Minikel, Deborah E. Cabin
Abstract
There is an urgent need to develop drugs for prion disease, a currently untreatable neurodegenerative disease. In this effort, there is a debate over which animal models can best support a drug development program. While the study of prion disease benefits from excellent animal models because prions naturally afflict many different mammals, different models have different capabilities and limitations. Here, we conducted a therapeutic efficacy study of the drug candidate anle138b in mouse models with two of the most common mutations that cause genetic prion disease. In a more typical model where prions are injected directly into the brain, we found anle138b to be effective. In the genetic models, however, the animals never reached a clear, measurable point of disease onset. We conclude that not all prion disease animal models are ideally suited to drug efficacy studies, and well-defined, quantitative disease metrics should be a priority.