{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,14]],"date-time":"2026-11-14T07:23:39Z","timestamp":1794641019393,"version":"4.9.1"},"reference-count":88,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Parkinson\u2019s Disease"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>Intracerebral delivery of glial cell line-derived neurotrophic factor (GDNF) therapeutics continues to show promise, especially in Parkinson's disease (PD). However, randomized, placebo-controlled clinical trials using GDNF protein have been inconclusive to date. A major sham-surgery controlled trial using GDNF gene therapy commenced in 2024. In this review we aim to update the reader on the evolution and current state of the art of intracerebral delivery methods for GDNF protein and gene therapy in PD clinical trials. Our intent is to increase the awareness for the importance, subtleties, and pitfalls of intracerebral delivery when reviewing current available results for these therapies and their prospects going forward. We will compare and contrast GDNF protein infusion versus gene therapy strategies and define specific anatomical and physiological details in trial participants that continue to challenge clinicians and investigators attempting to maximize therapeutic coverage of the target putamen. Despite a growing consensus that convection-enhanced delivery (CED) is the optimal intracerebral infusion strategy for localized administration of therapeutics in general and gene therapy products in particular, there is less agreement on the need for related methods, such as the co-infusion of a gadolinium contrast agent and use of intraoperative magnetic resonance imaging (iMRI) to visualize the therapeutic distribution for optimizing target coverage. Whereas certain debates will continue, most investigators and clinicians respond positively to well-designed trials providing clean, conclusive results. Information included in this review is intended to provide additional insights to interested readers, allowing better assessment of details associated with upcoming GDNF therapeutic investigations.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Plain language summary title<\/jats:title>\n                    <jats:p>Clinical Delivery Methods for Treatments Based on Glial Cell Line-Derived Neurotrophic Factor (GDNF) in Parkinson's Disease<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1877718x261444841","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T02:59:31Z","timestamp":1778122771000},"page":"629-645","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical GDNF delivery methods for Parkinson's disease"],"prefix":"10.1177","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6646-3655","authenticated-orcid":false,"given":"Matthias","family":"Luz","sequence":"first","affiliation":[{"name":"ML Clinical Solutions, Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8376-1934","authenticated-orcid":false,"given":"Massimo S","family":"Fiandaca","sequence":"additional","affiliation":[{"name":"Gene Therapy Institute, The Ohio State University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0424-3566","authenticated-orcid":false,"given":"Krystof S","family":"Bankiewicz","sequence":"additional","affiliation":[{"name":"Gene Therapy Institute, The Ohio State University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8493557"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn812"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-202004"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/1877718X241301041"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25344"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.01.004"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0040-1713874"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm850"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20374"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2007.106.4.614"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2005.102.2.0216"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27724"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2022.08.003"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz023"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-191576"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20737"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70254-4"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24436"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70065-6"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(25)00125-5"},{"key":"e_1_3_3_22_2","article-title":"Emerging gene therapies for Alzheimer's and Parkinson's diseases: an overview of clinical trials and promising candidates","volume":"16","author":"Roberts WS","year":"2024","unstructured":"Roberts WS, Price S, Wu M, et al. 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