title: Focusing brain therapeutic interventions in space and time for Parkinson's disease.
abstract: The last decade has seen major progress at all levels of neuroscience, from genes and molecules up to integrated systems-level models of brain function. In particular, there have been advances in the understanding of cell-type-specific contributions to function, together with a clearer account of how these contributions are coordinated from moment to moment to organise behavior. A major current endeavor is to leverage this knowledge to develop new therapeutic approaches. In Parkinson's disease, there are a number of promising emerging treatments. Here, we will highlight three ambitious novel therapeutic approaches for this condition, each robustly driven by primary neuroscience. Pharmacogenetics genetically re-engineers neurons to produce neurotrophins that are neuroprotective to vulnerable dopaminergic cells or to directly replace dopamine through enzyme transduction. Deep brain stimulation (DBS) is undergoing a transformation, with adaptive DBS controlled by neural signals resulting in better motor outcomes and significant reductions in overall stimulation that could reduce side effects. Finally, optogenetics presents the opportunity to achieve cell-type-specific control with a high temporal specification on a large enough scale to effectively repair network-level dysfunction.
authors.affiliation: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, OX3 9DU, UK.
authors.forename: S
authors.initials: S
authors.lastname: Little
authors.affiliation: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, OX3 9DU, UK. Electronic address: peter.brown@ndcn.ox.ac.uk.
authors.forename: P
authors.initials: P
authors.lastname: Brown
mesh_terms: D001921:Brain / Q000503:physiopathology*; D046690:Deep Brain Stimulation; D006801:Humans; D062308:Optogenetics; D010300:Parkinson Disease / Q000628:therapy*; D010597:Pharmacogenetics