{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:53:24Z","timestamp":1790618004613,"version":"4.1.0"},"reference-count":337,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T00:00:00Z","timestamp":1664323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Understanding the pathophysiology and genetic background of Parkinson\u2019s disease (PD) increases the likelihood of developing effective disease-modifying therapeutic strategies. In particular, the discovery of genetic variants causing or increasing the risk for PD has contributed to refining the clinical, biological, and molecular classification of the disease and has offered new insights into sporadic forms. It is even more evident that specific genetic mutations can show different responses to pharmacological and device-aided therapies. To date, several agents acting on multiple PD-causing pathogenic pathways have been tested as disease-modifying strategies, with disappointing results. This may be caused by the recruitment of PD populations whose underlying molecular pathophysiology is heterogeneous. We believe that an effective model of personalized medicine must be prioritized in the near future. Here, we review the current therapeutic options under clinical and preclinical development for PD and discuss the key pending questions and challenges to face for successful clinical trials. Furthermore, we provide some insights into the role of genetics in guiding the decision-making process on symptomatic and device-aided therapies for PD in daily clinical practice.<\/jats:p>","DOI":"10.3390\/brainsci12101308","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T20:58:47Z","timestamp":1664398727000},"page":"1308","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Precision Medicine in Parkinson\u2019s Disease: From Genetic Risk Signals to Personalized Therapy"],"prefix":"10.3390","volume":"12","author":[{"given":"Giulia","family":"Straccia","sequence":"first","affiliation":[{"name":"Neurology and Stroke Unit, Centro Traumatologico Ortopedico (C.T.O) Hospital, A.O.R.N., Ospedali dei Colli, 80131 Naples, Italy"},{"name":"Fondazione IRCCS Istituto Neurologico Carlo Besta, Department of Clinical Neurosciences, Parkinson and Movement Disorders Unit, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1945-8153","authenticated-orcid":false,"given":"Fabiana","family":"Colucci","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Neurologico Carlo Besta, Department of Clinical Neurosciences, Parkinson and Movement Disorders Unit, 20133 Milan, Italy"},{"name":"Dipartimento di Neuroscienze e Riabilitazione, Universit\u00e0 degli Studi di Ferrara, 44100 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Eleopra","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Neurologico Carlo Besta, Department of Clinical Neurosciences, Parkinson and Movement Disorders Unit, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1990-1939","authenticated-orcid":false,"given":"Roberto","family":"Cilia","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Neurologico Carlo Besta, Department of Clinical Neurosciences, Parkinson and Movement Disorders Unit, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1001\/jamaneurol.2017.3299","article-title":"The Parkinson Pandemic\u2014A Call to Action","volume":"75","author":"Dorsey","year":"2018","journal-title":"JAMA Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6469","DOI":"10.1073\/pnas.95.11.6469","article-title":"\u03b1-Synuclein in filamentous inclusions of Lewy bodies from Parkinson\u2019s disease and dementia with Lewy bodies","volume":"95","author":"Spillantini","year":"1998","journal-title":"Proc. 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