title: Challenges of modifying disease progression in prediagnostic Parkinson's disease.
abstract: Neurodegeneration in Parkinson's disease starts years before a clinical diagnosis can be reliably made. The prediagnostic phase of the disease offers a window of opportunity in which disease-modifying therapies-ie, those aimed at delaying or preventing the progression to overt disease and its many complications-could be most beneficial, but no such therapies are available at present. The unravelling of the mechanisms of neurodegeneration from the earliest stages, however, could lead to the development of new interventions whose therapeutic potential will need to be assessed in adequately designed clinical trials. Advances in the understanding of this prediagnostic phase of Parkinson's disease (for which the clinical diagnostic and prognostic markers used in more advanced disease stages are not applicable) will lead to the identification of biomarkers of neurodegeneration and its progression. These biomarkers will, in turn, help to identify the optimum population to be included and the most appropriate outcomes to be assessed in trials of disease-modifying drugs. Potential risks to minimally symptomatic participants, some of whom might not progress to manifest Parkinson's disease, and individuals who do not wish to know their mutation carrier status, could pose specific ethical dilemmas in the design of these trials.
authors.affiliation: Neurology Service, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Salat
authors.affiliation: Reta Lila Weston Institute for Neurological Studies, UCL Institute of Neurology, London, UK.
authors.forename: Alastair J
authors.initials: AJ
authors.lastname: Noyce
authors.affiliation: Department of Clinical Neurosciences, UCL Institute of Neurology, London, UK.
authors.forename: Anette
authors.initials: A
authors.lastname: Schrag
authors.affiliation: Parkinson's Disease Research, August Pi i Sunyer Biomedical Research Institute, University of Barcelona, Barcelona, Spain; Parkinson Disease and Movement Disorder Unit, Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Universidad de Barcelona, Barcelona, Spain. Electronic address: etolosa@clinic.ub.es.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tolosa
mesh_terms: D015415:Biomarkers; D018450:Disease Progression; D006801:Humans; D010300:Parkinson Disease / Q000175:diagnosis*; D062706:Prodromal Symptoms
chemical_list: D015415:Biomarkers