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The Michael J. Fox Foundation’s Efforts to Generate, Characterize, and Promote the Use of a Variety of Preclinical Models of Parkinson’s Disease

Preclinical models are a necessary tool for investigating the pathogenesis and potential therapeutic strategies for diseases like Parkinson’s disease (PD). As the precise etiology of PD is currently unknown and appears to vary among individuals, numerous preclinical models are available to study this disease. To ensure the research community has access to well-validated models of PD, The Michael J. Fox Foundation (MJFF) has taken an active role in designing, validating, and distributing various models of PD that rely on different genetic or interventional manipulations to induce a model of PD that can be used to investigate mechanisms of PD neurodegeneration or strategies for preventing, slowing, or halting disease progression. Here we summarize MJFF-led efforts to develop and validate three different types of PD preclinical models: the alpha-synuclein (aSyn) pre-formed fibril model, an aSyn knockdown model using viral vectors, and genetic models of PD. We will include information on the three species of aSyn monomers for PFF generation that MJFF has developed, as well as data validating the toxicity of these PFF species and best practices for generating and validating aSyn PFFs before use in in vitro or in vivo models. Data will also be presented from validation studies investigating the MJFF-generated aSyn knockdown viral vectors that specifically target mouse or human wildtype aSyn (in addition to common mutant forms of aSyn). For more information on the MJFF-led efforts to characterize and provide well-validated preclinical models of PD, an outline of our characterization plan for genetic animal models of PD and available resources for help in choosing an animal model will be highlighted as well. Ultimately, MJFF’s investment in providing the research community with robust, well-characterized animal models and information on choosing an appropriate model will hopefully lead to advancements in PD research. 

Authors: Nicole K. Polinski, Terina N. Martinez, Lindsey Gottler, Steve Marshall, Kelvin C. Luk, Caryl E. Sortwell, Kelly Dakin, Allesia Krank, Amasi Kumeh, Allison L. Morris, Kuldip D. Dave

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