{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:38:18Z","timestamp":1793036298078,"version":"4.5.0"},"reference-count":104,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T00:00:00Z","timestamp":1596153600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014461","name":"NIHR Biomedical Research Centre","doi-asserted-by":"publisher","award":["146281"],"award-info":[{"award-number":["146281"]}],"id":[{"id":"10.13039\/100014461","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["203151\/Z\/16\/Z"],"award-info":[{"award-number":["203151\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["NF-SI-0616-10011"],"award-info":[{"award-number":["NF-SI-0616-10011"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203151\/Z\/16\/Z"],"award-info":[{"award-number":["203151\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>Parkinson\u2019s disease (PD) is a common neurodegenerative disease typified by a movement disorder consisting of bradykinesia, rest tremor, rigidity, and postural instability. Treatment options for PD are limited, with most of the current approaches based on restoration of dopaminergic tone in the striatum. However, these do not alter disease course and do not treat the non-dopamine-dependent features of PD such as freezing of gait, cognitive impairment, and other non-motor features of the disorder, which often have the greatest impact on quality of life. As understanding of PD pathogenesis grows, novel therapeutic avenues are emerging. These include treatments that aim to control the symptoms of PD without the problematic side effects seen with currently available treatments and those that are aimed towards slowing pathology, reducing neuronal loss, and attenuating disease course. In this latter regard, there has been much interest in drug repurposing (the use of established drugs for a new indication), with many drugs being reported to affect PD-relevant intracellular processes. This approach offers an expedited route to the clinic, given that pharmacokinetic and safety data are potentially already available. In terms of better symptomatic therapies that are also regenerative, gene therapies and cell-based treatments are beginning to enter clinical trials, and developments in other neurosurgical strategies such as more nuanced deep brain stimulation approaches mean that the landscape of PD treatment is likely to evolve considerably over the coming years. In this review, we provide an overview of the novel therapeutic approaches that are close to, or are already in, clinical trials.<\/ns4:p>","DOI":"10.12688\/f1000research.25634.1","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T07:20:08Z","timestamp":1596180008000},"page":"862","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":163,"title":["Recent developments in the treatment of Parkinson's Disease"],"prefix":"10.12688","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5186-7630","authenticated-orcid":false,"given":"Thomas B","family":"Stoker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger A","family":"Barker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2020,7,31]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"896-912","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson's disease.","volume":"386","author":"L Kalia","year":"2015","journal-title":"Lancet."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"a009258","DOI":"10.1101\/cshperspect.a009258","article-title":"Parkinson's disease and parkinsonism: Neuropathology.","volume":"2","author":"D Dickson","year":"2012","journal-title":"Cold Spring Harb Perspect Med."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"2947-57","DOI":"10.1093\/brain\/awp234","article-title":"A clinico-pathological study of subtypes in Parkinson's disease.","volume":"132","author":"M Selikhova","year":"2009","journal-title":"Brain."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"171-222","DOI":"10.1124\/pr.111.005678","article-title":"The pharmacology of L-DOPA-induced dyskinesia in Parkinson's disease.","volume":"65","author":"P Huot","year":"2013","journal-title":"Pharmacol Rev."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"S3-S7","DOI":"10.1097\/00019052-200312001-00002","article-title":"Dopamine agonists, receptor selectivity and dyskinesia induction in Parkinson's disease.","volume":"16 Suppl 1","author":"P Jenner","year":"2003","journal-title":"Curr Opin Neurol."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"1258-64","DOI":"10.1136\/jnnp-2013-305277","article-title":"The CamPaIGN study of Parkinson's disease: 10-year outlook in an incident population-based cohort.","volume":"84","author":"C Williams-Gray","year":"2013","journal-title":"J Neurol Neurosurg Psychiatr."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"185-90","DOI":"10.1002\/mds.27882","article-title":"Motor complications in Parkinson's disease: 13-year follow-up of the CamPaIGN cohort.","volume":"35","author":"H Kim","year":"2020","journal-title":"Mov Disord."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"197-211","DOI":"10.1016\/s0197-4580(02)00065-9","article-title":"Staging of brain pathology related to sporadic Parkinson\u2019s disease.","volume":"24","author":"H Braak","year":"2003","journal-title":"Neurobiol Aging."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"374-9","DOI":"10.1056\/NEJM196702162760703","article-title":"Aromatic amino acids and modification of parkinsonism.","volume":"276","author":"G Cotzias","year":"1967","journal-title":"N Engl J Med."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"839-40","DOI":"10.1038\/42166","article-title":"Alpha-Synuclein in Lewy bodies.","volume":"388","author":"M Spillantini","year":"1997","journal-title":"Nature."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"2045-7","DOI":"10.1126\/science.276.5321.2045","article-title":"Mutation in the -Synuclein Gene Identified in Families with Parkinson's Disease.","volume":"276","author":"M Polymeropoulos","year":"1997","journal-title":"Science."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"949-53","DOI":"10.1126\/science.1227157","article-title":"Pathological -Synuclein Transmission Initiates Parkinson-like Neurodegeneration in Nontransgenic Mice.","volume":"338","author":"K Luk","year":"2012","journal-title":"Science."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"521-33","DOI":"10.1016\/s0896-6273(02)00682-7","article-title":"Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein in pubmed.","volume":"34","author":"B Giasson","year":"2002","journal-title":"Neuron."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"299","DOI":"10.3389\/fnmol.2019.00299","article-title":"Targeting Alpha-Synuclein as a Therapy for Parkinson's Disease.","volume":"12","author":"C Fields","year":"2019","journal-title":"Front Mol Neurosci."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"273-7","DOI":"10.1038\/s41586-020-1984-7","article-title":"Discriminating \u03b1-synuclein strains in Parkinson\u2019s disease and multiple system atrophy.","volume":"578","author":"M Shahnawaz","year":"2020","journal-title":"Nature."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"382-90","DOI":"10.1016\/j.expneurol.2005.12.024","article-title":"Silencing of human alpha-synuclein in vitro and in rat brain using lentiviral-mediated RNAi.","volume":"198","author":"M Sapru","year":"2006","journal-title":"Exp Neurol."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/1750-1326-3-19","article-title":"In vivo silencing of alpha-synuclein using naked siRNA.","volume":"3","author":"J Lewis","year":"2008","journal-title":"Mol Neurodegener."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"e12122","DOI":"10.1371\/journal.pone.0012122","article-title":"Alpha-synuclein suppression by targeted small interfering RNA in the primate substantia nigra.","volume":"5","author":"A McCormack","year":"2010","journal-title":"PLoS One."},{"key":"ref-19","doi-asserted-by":"publisher","first-page":"211-8","DOI":"10.1002\/mds.26878","article-title":"First-in-human assessment of PRX002, an anti-\u03b1-synuclein monoclonal antibody, in healthy volunteers.","volume":"32","author":"D Schenk","year":"2017","journal-title":"Mov Disord."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"1206-14","DOI":"10.1001\/jamaneurol.2018.1487","article-title":"Safety and Tolerability of Multiple Ascending Doses of PRX002\/RG7935, an Anti-\u03b1-Synuclein Monoclonal Antibody, in Patients With Parkinson Disease: A Randomized Clinical Trial.","volume":"75","author":"J Jankovic","year":"2018","journal-title":"JAMA Neurol."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"276-88","DOI":"10.1016\/j.nbd.2018.10.016","article-title":"Development of an aggregate-selective, human-derived \u03b1-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson's disease models.","volume":"124","author":"A Weihofen","year":"2019","journal-title":"Neurobiol Dis."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"1154-63","DOI":"10.1002\/mds.27738","article-title":"Randomized phase I clinical trial of anti-\u03b1\u2010synuclein antibody BIIB054.","volume":"34","author":"M Brys","year":"2019","journal-title":"Mov Disord."},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"1023-31","DOI":"10.1016\/j.ymthe.2004.08.019","article-title":"A human single-chain Fv intrabody blocks aberrant cellular effects of overexpressed alpha-synuclein.","volume":"10","author":"C Zhou","year":"2004","journal-title":"Mol Ther."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"1126-36","DOI":"10.1111\/j.1471-4159.2004.02378.x","article-title":"Developmental loss and resistance to MPTP toxicity of dopaminergic neurones in substantia nigra pars compacta of gamma-synuclein, alpha-synuclein and double alpha\/gamma-synuclein null mutant mice.","volume":"89","author":"D Robertson","year":"2004","journal-title":"J Neurochem."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"249-67","DOI":"10.3233\/JPD-012138","article-title":"Loss of Functional Alpha-Synuclein: A Toxic Event in Parkinson's Disease?","volume":"2","author":"N Kanaan","year":"2012","journal-title":"J Parkinsons Dis."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"1450-7","DOI":"10.1038\/mt.2010.115","article-title":"In Vivo RNAi-Mediated \u03b1-Synuclein Silencing Induces Nigrostriatal Degeneration.","volume":"18","author":"O Gorbatyuk","year":"2010","journal-title":"Mol Ther."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"36","DOI":"10.3389\/fnmol.2018.00036","article-title":"Silencing Alpha Synuclein in Mature Nigral Neurons Results in Rapid Neuroinflammation and Subsequent Toxicity.","volume":"11","author":"M Benskey","year":"2018","journal-title":"Front Mol Neurosci."},{"key":"ref-28","doi-asserted-by":"publisher","first-page":"891-8","DOI":"10.1126\/science.aaf3934","article-title":"\u03b22-Adrenoreceptor is a regulator of the \u03b1-synuclein gene driving risk of Parkinson's disease.","volume":"357","author":"S Mittal","year":"2017","journal-title":"Science."},{"key":"ref-29","doi-asserted-by":"publisher","first-page":"326-38","DOI":"10.1002\/jnr.21483","article-title":"Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of Parkinson's disease.","volume":"86","author":"G Bertilsson","year":"2008","journal-title":"J Neurosci Res."},{"key":"ref-30","doi-asserted-by":"publisher","first-page":"1285-90","DOI":"10.1073\/pnas.0806720106","article-title":"GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism.","volume":"106","author":"Y Li","year":"2009","journal-title":"Proc Natl Acad Sci U S A."},{"key":"ref-31","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/1742-2094-5-19","article-title":"Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson's disease.","volume":"5","author":"A Harkavyi","year":"2008","journal-title":"J Neuroinflammation."},{"key":"ref-32","doi-asserted-by":"publisher","first-page":"802-18","DOI":"10.1016\/j.drudis.2016.01.013","article-title":"The glucagon-like peptide 1 (GLP) receptor as a therapeutic target in Parkinson's disease: Mechanisms of action.","volume":"21","author":"D Athauda","year":"2016","journal-title":"Drug Discov Today."},{"key":"ref-33","doi-asserted-by":"publisher","first-page":"337-44","DOI":"10.3233\/JPD-140364","article-title":"Motor and Cognitive Advantages Persist 12 Months After Exenatide Exposure in Parkinson\u2019s Disease.","volume":"4","author":"I Aviles-Olmos","year":"2014","journal-title":"J Parkinsons Dis."},{"key":"ref-40","doi-asserted-by":"publisher","first-page":"1664-75","DOI":"10.1016\/S0140-6736(17)31585-4","article-title":"Exenatide once weekly versus placebo in Parkinson's disease: A randomised, double-blind, placebo-controlled trial.","volume":"390","author":"D Athauda","year":"2017","journal-title":"Lancet."},{"key":"ref-34","doi-asserted-by":"publisher","first-page":"4874","DOI":"10.1038\/srep04874","article-title":"The c-Abl inhibitor, nilotinib, protects dopaminergic neurons in a preclinical animal model of Parkinson's disease.","volume":"4","author":"S Karuppagounder","year":"2014","journal-title":"Sci Rep."},{"key":"ref-35","doi-asserted-by":"publisher","first-page":"4539-49","DOI":"10.1172\/JCI129987","article-title":"Enhancing glycolysis attenuates Parkinson\u2019s disease progression in models and clinical databases.","volume":"129","author":"R Cai","year":"2019","journal-title":"J Clin Invest."},{"key":"ref-36","doi-asserted-by":"publisher","first-page":"158-67","DOI":"10.1002\/jcph.1008","article-title":"Repeated-Dose Oral N-Acetylcysteine in Parkinson's Disease: Pharmacokinetics and Effect on Brain Glutathione and Oxidative Stress.","volume":"58","author":"L Coles","year":"2018","journal-title":"J Clin Pharmacol."},{"key":"ref-37","doi-asserted-by":"publisher","first-page":"1-10","DOI":"10.1016\/j.jneuroim.2013.10.009","article-title":"GM-CSF induces neuroprotective and anti-inflammatory responses in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxicated mice.","volume":"265","author":"L Kosloski","year":"2013","journal-title":"J Neuroimmunol."},{"key":"ref-38","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41531-017-0013-5","article-title":"Evaluation of the safety and immunomodulatory effects of sargramostim in a randomized, double-blind phase 1 clinical Parkinson's disease trial.","volume":"3","author":"H Gendelman","year":"2017","journal-title":"NPJ Parkinsons Dis."},{"key":"ref-39","doi-asserted-by":"publisher","first-page":"2687-700","DOI":"10.1093\/brain\/awv184","article-title":"Effect of the myeloperoxidase inhibitor AZD3241 on microglia: A PET study in Parkinson's disease.","volume":"138","author":"A Jucaite","year":"2015","journal-title":"Brain."},{"key":"ref-41","doi-asserted-by":"publisher","first-page":"364-71","DOI":"10.1016\/j.nbd.2011.04.007","article-title":"The L-type channel antagonist isradipine is neuroprotective in a mouse model of Parkinson's disease.","volume":"43","author":"E Ilijic","year":"2011","journal-title":"Neurobiol Dis."},{"key":"ref-42","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1038\/s41598-017-01402-2","article-title":"Brain iron chelation by deferiprone in a phase 2 randomised double-blinded placebo controlled clinical trial in Parkinson\u2019s disease.","volume":"7","author":"A Martin-Bastida","year":"2017","journal-title":"Sci Rep."},{"key":"ref-43","doi-asserted-by":"publisher","first-page":"503-17","DOI":"10.3233\/JPD-160867","article-title":"Nilotinib Effects in Parkinson\u2019s disease and Dementia with Lewy bodies.","volume":"6","author":"F Pagan","year":"2016","journal-title":"J Parkinsons Dis."},{"key":"ref-44","doi-asserted-by":"publisher","first-page":"79-80","DOI":"10.3233\/JPD-160975","article-title":"Could MAO-B Inhibitor Withdrawal Rather than Nilotinib Benefit Explain the Dopamine Metabolite Increase in Parkinsonian Study Subjects?","volume":"7","author":"M Schwarzschild","year":"2017","journal-title":"J Parkinsons Dis."},{"key":"ref-45","doi-asserted-by":"publisher","first-page":"e00470","DOI":"10.1002\/prp2.470","article-title":"Pharmacokinetics and pharmacodynamics of a single dose Nilotinib in individuals with Parkinson's disease.","volume":"7","author":"F Pagan","year":"2019","journal-title":"Pharmacol Res Perspect."},{"key":"ref-46","doi-asserted-by":"publisher","first-page":"19-25","DOI":"10.1038\/nchembio.1657","article-title":"Terazosin activates Pgk1 and Hsp90 to promote stress resistance.","volume":"11","author":"X Chen","year":"2015","journal-title":"Nat Chem Biol."},{"key":"ref-47","doi-asserted-by":"publisher","first-page":"3038-50","DOI":"10.1093\/brain\/awt224","article-title":"Ursocholanic acid rescues mitochondrial function in common forms of familial Parkinson's disease.","volume":"136","author":"H Mortiboys","year":"2013","journal-title":"Brain."},{"key":"ref-48","doi-asserted-by":"publisher","first-page":"846-52","DOI":"10.1212\/WNL.0000000000001905","article-title":"UDCA exerts beneficial effect on mitochondrial dysfunction in LRRK2G2019S carriers and in vivo.","volume":"85","author":"H Mortiboys","year":"2015","journal-title":"Neurology."},{"key":"ref-49","doi-asserted-by":"publisher","first-page":"810-7","DOI":"10.1007\/s12035-014-9043-8","article-title":"Ursodeoxycholic Acid Ameliorates Apoptotic Cascade in the Rotenone Model of Parkinson's Disease: Modulation of Mitochondrial Perturbations.","volume":"53","author":"N Abdelkader","year":"2016","journal-title":"Mol Neurobiol."},{"key":"ref-50","doi-asserted-by":"publisher","first-page":"392-9","DOI":"10.1093\/brain\/aws318","article-title":"Glucocerebrosidase mutations influence the natural history of Parkinson's disease in a community-based incident cohort.","volume":"136","author":"S Winder-Rhodes","year":"2013","journal-title":"Brain."},{"key":"ref-51","doi-asserted-by":"publisher","first-page":"1515-7","DOI":"10.1016\/j.neurobiolaging.2007.11.016","article-title":"Complete screening for glucocerebrosidase mutations in Parkinson disease patients from Portugal.","volume":"30","author":"J Bras","year":"2009","journal-title":"Neurobiol Aging."},{"key":"ref-52","doi-asserted-by":"publisher","first-page":"1651-61","DOI":"10.1056\/NEJMoa0901281","article-title":"Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson's Disease.","volume":"361","author":"E Sidransky","year":"2009","journal-title":"N Engl J Med."},{"key":"ref-53","doi-asserted-by":"publisher","first-page":"37-52","DOI":"10.1016\/j.cell.2011.06.001","article-title":"Gaucher disease glucocerebrosidase and \u03b1-synuclein form a bidirectional pathogenic loop in synucleinopathies.","volume":"146","author":"J Mazzulli","year":"2011","journal-title":"Cell."},{"key":"ref-54","doi-asserted-by":"publisher","first-page":"342-56","DOI":"10.1016\/j.stemcr.2016.01.013","article-title":"ER Stress and Autophagic Perturbations Lead to Elevated Extracellular \u03b1-Synuclein in GBA-N370S Parkinson's iPSC-Derived Dopamine Neurons.","volume":"6","author":"H Fernandes","year":"2016","journal-title":"Stem Cell Reports."},{"key":"ref-55","doi-asserted-by":"publisher","first-page":"1481-95","DOI":"10.1093\/brain\/awu020","article-title":"Ambroxol improves lysosomal biochemistry in glucocerebrosidase mutation-linked Parkinson disease cells.","volume":"137","author":"A McNeill","year":"2014","journal-title":"Brain."},{"key":"ref-56","doi-asserted-by":"publisher","first-page":"766-75","DOI":"10.1002\/ana.24790","article-title":"Ambroxol effects in glucocerebrosidase and \u03b1-synuclein transgenic mice.","volume":"80","author":"A Migdalska-Richards","year":"2016","journal-title":"Ann Neurol."},{"key":"ref-57","doi-asserted-by":"publisher","first-page":"427-434","DOI":"10.1001\/jamaneurol.2019.4611","article-title":"Ambroxol for the Treatment of Patients With Parkinson Disease With and Without Glucocerebrosidase Gene Mutations: A Nonrandomized, Noncontrolled Trial.","volume":"77","author":"S Mullin","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref-58","doi-asserted-by":"publisher","first-page":"1085-9","DOI":"10.1002\/mds.26278","article-title":"No evidence for substrate accumulation in Parkinson brains with GBA mutations.","volume":"30","author":"M Gegg","year":"2015","journal-title":"Mov Disord."},{"key":"ref-59","doi-asserted-by":"publisher","first-page":"644-59","DOI":"10.1002\/ana.24778","article-title":"Physiology of freezing of gait.","volume":"80","author":"A Snijders","year":"2016","journal-title":"Ann Neurol."},{"key":"ref-60","doi-asserted-by":"publisher","first-page":"S18-S23","DOI":"10.1212\/wnl.67.7_suppl_2.s18","article-title":"Safinamide: From molecular targets to a new anti-Parkinson drug.","volume":"67","author":"C Caccia","year":"2006","journal-title":"Neurology."},{"key":"ref-61","doi-asserted-by":"publisher","first-page":"204-223","DOI":"10.1038\/s41582-019-0155-7","article-title":"Emerging therapies in Parkinson disease \u2014 repurposed drugs and new approaches.","volume":"15","author":"A Elkouzi","year":"2019","journal-title":"Nat Rev Neurol."},{"key":"ref-62","doi-asserted-by":"publisher","first-page":"229-37","DOI":"10.1002\/mds.25751","article-title":"Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations.","volume":"29","author":"R Borgohain","year":"2014","journal-title":"Mov Disord."},{"key":"ref-63","doi-asserted-by":"publisher","first-page":"249-58","DOI":"10.1016\/S1474-4422(15)00389-0","article-title":"Rivastigmine for gait stability in patients with Parkinson's disease (ReSPonD): A randomised, double-blind, placebo-controlled, phase 2 trial.","volume":"15","author":"E Henderson","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref-64","doi-asserted-by":"publisher","first-page":"1263-9","DOI":"10.1212\/WNL.0b013e3181f6128c","article-title":"Effects of a central cholinesterase inhibitor on reducing falls in Parkinson disease.","volume":"75","author":"K Chung","year":"2010","journal-title":"Neurology."},{"key":"ref-65","doi-asserted-by":"publisher","first-page":"1-7","DOI":"10.1016\/j.neures.2007.05.002","article-title":"Immunohistochemical detection of l-DOPA-derived dopamine within serotonergic fibers in the striatum and the substantia nigra pars reticulata in Parkinsonian model rats.","volume":"59","author":"H Yamada","year":"2007","journal-title":"Neurosci Res."},{"key":"ref-66","doi-asserted-by":"publisher","first-page":"1088-96","DOI":"10.1002\/mds.25366","article-title":"Study of the antidyskinetic effect of eltoprazine in animal models of levodopa-induced dyskinesia.","volume":"28","author":"E Bezard","year":"2013","journal-title":"Mov Disord."},{"key":"ref-67","doi-asserted-by":"publisher","first-page":"1740-9","DOI":"10.1002\/mds.100","article-title":"Diverse serotonin actions of vilazodone reduce l-3,4-dihidroxyphenylalanine-induced dyskinesia in hemi-parkinsonian rats.","volume":"33","author":"S Meadows","year":"2018","journal-title":"Mov Disord."},{"key":"ref-68","doi-asserted-by":"publisher","first-page":"58-62","DOI":"10.1097\/00002826-200403000-00003","article-title":"Multicenter, open-label, trial of sarizotan in Parkinson disease patients with levodopa-induced dyskinesias (the SPLENDID Study).","volume":"27","author":"C Olanow","year":"2004","journal-title":"Clin Neuropharmacol."},{"key":"ref-69","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s40478-018-0653-7","article-title":"Regulation of dopamine neurotransmission from serotonergic neurons by ectopic expression of the dopamine D2 autoreceptor blocks levodopa-induced dyskinesia.","volume":"7","author":"R Sellnow","year":"2019","journal-title":"Acta Neuropathol Commun."},{"key":"ref-70","doi-asserted-by":"publisher","first-page":"1554-66","DOI":"10.1046\/j.1460-9568.1999.00566.x","article-title":"Protection and regeneration of nigral dopaminergic neurons by neurturin or GDNF in a partial lesion model of Parkinson's disease after administration into the striatum or the lateral ventricle.","volume":"11","author":"C Rosenblad","year":"1999","journal-title":"Eur J Neurosci."},{"key":"ref-71","first-page":"1396-401","article-title":"Dose response to intraventricular glial cell line-derived neurotrophic factor administration in parkinsonian monkeys.","volume":"282","author":"Z Zhang","year":"1997","journal-title":"J Pharmacol Exp Ther."},{"key":"ref-72","doi-asserted-by":"publisher","first-page":"216-22","DOI":"10.3171\/jns.2005.102.2.0216","article-title":"Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line\u2014derived neurotrophic factor.","volume":"102","author":"J Slevin","year":"2005","journal-title":"J Neurosurg."},{"key":"ref-73","doi-asserted-by":"publisher","first-page":"298-302","DOI":"10.1002\/ana.20374","article-title":"Intraputamenal infusion of glial cell line-derived neurotrophic factor in PD: A two-year outcome study.","volume":"57","author":"N Patel","year":"2005","journal-title":"Ann Neurol."},{"key":"ref-74","doi-asserted-by":"publisher","first-page":"312-4","DOI":"10.1038\/s41582-019-0180-6","article-title":"Parkinson disease and growth factors \u2014 is GDNF good enough?","volume":"15","author":"A Kirkeby","year":"2019","journal-title":"Nat Rev Neurol."},{"key":"ref-75","doi-asserted-by":"publisher","first-page":"459-66","DOI":"10.1002\/ana.20737","article-title":"Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease.","volume":"59","author":"A Lang","year":"2006","journal-title":"Ann Neurol."},{"key":"ref-76","doi-asserted-by":"publisher","first-page":"512-25","DOI":"10.1093\/brain\/awz023","article-title":"Randomized trial of intermittent intraputamenal glial cell line-derived neurotrophic factor in Parkinson's disease.","volume":"142","author":"A Whone","year":"2019","journal-title":"Brain."},{"key":"ref-77","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-202004","article-title":"GDNF and Parkinson's Disease: Where Next? A Summary from a Recent Workshop.","author":"R Barker","year":"2020","journal-title":"J Parkinsons Dis."},{"key":"ref-78","doi-asserted-by":"publisher","first-page":"400-8","DOI":"10.1016\/S1474-4422(08)70065-6","article-title":"Safety and tolerability of intraputaminal delivery of CERE-120 (adeno-associated virus serotype 2-neurturin) to patients with idiopathic Parkinson's disease: An open-label, phase I trial.","volume":"7","author":"J Marks","year":"2008","journal-title":"Lancet Neurol."},{"key":"ref-79","doi-asserted-by":"publisher","first-page":"1164-72","DOI":"10.1016\/S1474-4422(10)70254-4","article-title":"Gene delivery of AAV2-neurturin for Parkinson's disease: A double-blind, randomised, controlled trial.","volume":"9","author":"W Marks","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref-80","doi-asserted-by":"publisher","first-page":"248-57","DOI":"10.1002\/ana.24436","article-title":"Gene delivery of neurturin to putamen and substantia nigra in Parkinson disease: A double-blind, randomized, controlled trial.","volume":"78","author":"C Olanow","year":"2015","journal-title":"Ann Neurol."},{"key":"ref-81","doi-asserted-by":"publisher","first-page":"1698-701","DOI":"10.1212\/WNL.0b013e3182904faa","article-title":"Safety\/feasibility of targeting the substantia nigra with AAV2-neurturin in Parkinson patients.","volume":"80","author":"R Bartus","year":"2013","journal-title":"Neurology."},{"key":"ref-82","doi-asserted-by":"publisher","first-page":"569-73","DOI":"10.1016\/j.stem.2017.09.014","article-title":"Human Trials of Stem Cell-Derived Dopamine Neurons for Parkinson\u2019s Disease: Dawn of a New Era.","volume":"21","author":"R Barker","year":"2017","journal-title":"Cell Stem Cell."},{"key":"ref-83","doi-asserted-by":"publisher","first-page":"704-14","DOI":"10.1002\/ana.25450","article-title":"Magnetic resonance imaging-guided phase 1 trial of putaminal AADC gene therapy for Parkinson's disease.","volume":"85","author":"C Christine","year":"2019","journal-title":"Ann Neurol."},{"key":"ref-84","doi-asserted-by":"publisher","first-page":"1138-46","DOI":"10.1016\/S0140-6736(13)61939-X","article-title":"Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: A dose escalation, open-label, phase 1\/2 trial.","volume":"383","author":"S Palfi","year":"2014","journal-title":"Lancet."},{"key":"ref-85","doi-asserted-by":"publisher","first-page":"574-7","DOI":"10.1126\/science.2105529","article-title":"Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease.","volume":"247","author":"O Lindvall","year":"1990","journal-title":"Science."},{"key":"ref-86","doi-asserted-by":"publisher","first-page":"95-107","DOI":"10.1002\/ana.410420115","article-title":"Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson's disease.","volume":"42","author":"G Wenning","year":"1997","journal-title":"Ann Neurol."},{"key":"ref-87","doi-asserted-by":"publisher","first-page":"1380-90","DOI":"10.1093\/brain\/123.7.1380","article-title":"Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson's disease.","volume":"123","author":"P Brundin","year":"2000","journal-title":"Brain."},{"key":"ref-88","doi-asserted-by":"publisher","first-page":"329-34","DOI":"10.1038\/s41586-018-0087-1","article-title":"New approaches for brain repair\u2014from rescue to reprogramming.","volume":"557","author":"R Barker","year":"2018","journal-title":"Nature."},{"key":"ref-89","doi-asserted-by":"publisher","first-page":"57-63","DOI":"10.3233\/JPD-160798","article-title":"Are Stem Cell-Based Therapies for Parkinson's Disease Ready for the Clinic in 2016?","volume":"6","author":"R Barker","year":"2016","journal-title":"J Parkinsons Dis."},{"key":"ref-90","doi-asserted-by":"publisher","first-page":"15-6","DOI":"10.1038\/546015a","article-title":"Trials of embryonic stem cells to launch in China.","volume":"546","author":"D Cyranoski","year":"2017","journal-title":"Nature."},{"key":"ref-91","doi-asserted-by":"publisher","first-page":"374-80","DOI":"10.1097\/WCO.0b013e3283632d08","article-title":"Deep brain stimulation for Parkinson\u02bcs disease and other movement disorders.","volume":"26","author":"S Kalia","year":"2013","journal-title":"Curr Opin Neurol."},{"key":"ref-92","doi-asserted-by":"publisher","first-page":"1369-73","DOI":"10.1056\/NEJMp1408779","article-title":"Deep-brain stimulation--entering the era of human neural-network modulation.","volume":"371","author":"M Okun","year":"2014","journal-title":"N Engl J Med."},{"key":"ref-93","doi-asserted-by":"publisher","first-page":"581-91","DOI":"10.1016\/S1474-4422(10)70093-4","article-title":"Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson's disease (PD SURG trial): A randomised, open-label trial.","volume":"9","author":"A Williams","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref-94","doi-asserted-by":"publisher","first-page":"2077-91","DOI":"10.1056\/NEJMoa0907083","article-title":"Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease.","volume":"362","author":"K Follett","year":"2010","journal-title":"N Engl J Med."},{"key":"ref-95","doi-asserted-by":"publisher","first-page":"11986-93","DOI":"10.1523\/JNEUROSCI.1568-13.2013","article-title":"Gait disorders in parkinsonian monkeys with pedunculopontine nucleus lesions: A tale of two systems.","volume":"33","author":"D Grabli","year":"2013","journal-title":"J Neurosci."},{"key":"ref-96","doi-asserted-by":"publisher","first-page":"e463-e471","DOI":"10.1212\/WNL.0000000000005903","article-title":"Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease.","volume":"91","author":"M Hacker","year":"2018","journal-title":"Neurology."},{"key":"ref-97","doi-asserted-by":"publisher","first-page":"173","DOI":"10.3389\/fnins.2016.00173","article-title":"Deep Brain Stimulation: A Paradigm Shifting Approach to Treat Parkinson's Disease.","volume":"10","author":"P Hickey","year":"2016","journal-title":"Front Neurosci."},{"key":"ref-98","doi-asserted-by":"publisher","first-page":"1596-607","DOI":"10.1093\/brain\/awl346","article-title":"Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson's disease.","volume":"130","author":"A Stefani","year":"2007","journal-title":"Brain."},{"key":"ref-99","doi-asserted-by":"publisher","first-page":"2098-108","DOI":"10.1093\/brain\/awt122","article-title":"Nigral stimulation for resistant axial motor impairment in Parkinson\u2019s disease?: A randomized controlled trial.","volume":"136","author":"D Weiss","year":"2013","journal-title":"Brain."},{"key":"ref-100","doi-asserted-by":"publisher","first-page":"169-78","DOI":"10.1001\/jamaneurol.2017.3762","article-title":"Bilateral Deep Brain Stimulation of the Nucleus Basalis of Meynert for Parkinson Disease Dementia: A Randomized Clinical Trial.","volume":"75","author":"J Gratwicke","year":"2018","journal-title":"JAMA Neurol."},{"key":"ref-101","doi-asserted-by":"publisher","first-page":"783-92","DOI":"10.1002\/mds.27299","article-title":"Spinal Cord Stimulation Therapy for Gait Dysfunction in Advanced Parkinson's Disease Patients.","volume":"33","author":"O Samotus","year":"2018","journal-title":"Mov Disord."},{"key":"ref-102","doi-asserted-by":"publisher","first-page":"1750-8","DOI":"10.1002\/mds.26376","article-title":"Beta oscillations in freely moving Parkinson's subjects are attenuated during deep brain stimulation.","volume":"30","author":"E Quinn","year":"2015","journal-title":"Mov Disord."},{"key":"ref-103","doi-asserted-by":"publisher","first-page":"1029-1041.e16","DOI":"10.1016\/j.cell.2017.05.024","article-title":"Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields.","volume":"169","author":"N Grossman","year":"2017","journal-title":"Cell."},{"key":"ref-104","doi-asserted-by":"publisher","DOI":"10.1007\/s10143-019-01216-y","article-title":"Safety and efficacy of magnetic resonance imaging-guided focused ultrasound neurosurgery for Parkinson's disease: A systematic review.","author":"Y Xu","year":"2019","journal-title":"Neurosurg Rev."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/9-862\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/9-862\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/9-862\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T07:20:14Z","timestamp":1596180014000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/9-862\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,31]]},"references-count":104,"URL":"https:\/\/doi.org\/10.12688\/f1000research.25634.1","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.28292.r68462","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.28292.r68463","asserted-by":"subject"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,31]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/9-862\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.28292.r68463, Tipu Z. Aziz, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK, 31 Jul 2020, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/9-862\/v1#referee-response-68463","order":0,"name":"referee-response-68463","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.28292.r68462, Fredric P. Manfredsson, Parkinson's Disease Research Unit, Department of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona, USA, 31 Jul 2020, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/9-862\/v1#referee-response-68462","order":1,"name":"referee-response-68462","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The authors acknowledge financial support from the following organisations: Medical Research Council and Wellcome Trust Stem Cell Institute (Cambridge 203151\/Z\/16\/Z), National Institute for Health Research (NIHR) (NF-SI-0616-10011), NIHR Biomedical Research Centre (reference number 146281), and the Cure Parkinson\u2019s Trust. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}