title: Translational research for Parkinson׳s disease: The value of pre-clinical primate models.
abstract: Animal models have been highly questioned for their ability to predict the efficacy of different therapeutic strategies for neurodegenerative diseases. The increasing number of phase I/II clinical trials that fail to proceed to further stages of drug development has discredited the pertinence of such investigations. However, critical analysis of the data has often revealed errors and partially explained the lack of efficacy, opening the way to a refinement in designing pre-clinical studies. In parallel, many promising methods of drug delivery to the brain such as gene therapy or cell therapy have considerably advanced thanks to the clinical failures in the past 10 years. As methodological advances appear and knowledge becomes available, scientists will be faced with the choice of how to test new strategies or re-test old ones. With the hardening of social views and legislation regarding animal experimentation, there is increasing pressure to find alternative methods of assessment that predict efficacy (such as computational based models), or to perform efficacy trials directly in patients and only safety assays in animals. In this review we will focus on Parkinson׳s disease and on the impact of a body of data issued from NHP studies. We will attempt to critically examine the advantages and limitations of various approaches from the perspective of the animal model used to address specific questions.
authors.affiliation: MIRCen, CEA UMR 9199, 18 Route du Panorama, Fontenay-aux-Roses 92265, France.
authors.forename: Romina
authors.initials: R
authors.lastname: Aron Badin
authors.affiliation: CORIT (Consortium for Research in Organ Transplantation), Padua, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Vadori
authors.affiliation: CORIT (Consortium for Research in Organ Transplantation), Padua, Italy; Transplant Immunology Unit, Department of Transfusion Medicine, Padua University Hospital, Padua, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Cozzi
authors.affiliation: MIRCen, CEA UMR 9199, 18 Route du Panorama, Fontenay-aux-Roses 92265, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hantraye
mesh_terms: D000818:Animals; D017690:Cell Transplantation; D004195:Disease Models, Animal; D015316:Genetic Therapy; D006801:Humans; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011323:Primates; D013045:Species Specificity; D057170:Translational Research, Biomedical / Q000379:methods*
keywords: Cell transplantation; Functional assessment; NHP; Translational neuroscience; Viral vectors