{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T09:01:55Z","timestamp":1784710915976,"version":"3.55.0"},"reference-count":48,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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":["J Cent Nerv Syst Dis"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:p>Stem cell-based therapies for movement disorders show inconsistent translation due to variations in product characterisation, delivery, endpoints, safety, and follow-up. Regulatory guidance provides principles but lacks a unified trial framework. The objective was to create a practical framework that translates scientific, regulatory, manufacturing, ethical, and clinical expectations into an auditable pre\u2013First Patient In (FPI) checklist for stem cell trials. A structured review of the literature, clinical trials, and guidance documents was conducted. Searches were performed in PubMed\/MEDLINE, Embase, Google Scholar, and clinical trial registries, including ClinicalTrials.gov, Japan Registry, European Union Register, and Clinical Trials Registry\u2013India, until January 2026. Key guidance documents from the FDA, EMA, ICH, ISSCR, and selected PMDA sources were reviewed. Recurring requirements related to nonclinical evidence, manufacturing quality, ethics, trial design, safety, and follow-up were identified and translated into auditable pre-FPI checklist items. A framework was developed, structured as a universal Core Gate plus three risk-proportionate modules: Module A for pluripotent-derived neural grafts, Module B for somatic neural grafts, and Module C for mesenchymal stromal cell\/secretome approaches. The Core Gate outlines the minimum pre-FPI requirements across preclinical justification, GMP release documentation, regulatory and ethics readiness, patient selection, trial design, safety oversight, trial conduct, long-term follow-up, and transparency. The modules add platform-specific requirements according to biological and procedural risks, including tumourigenicity and genomic stability assessment, immunologic monitoring, and route-appropriate biodistribution and persistence expectations. Movement disorder-specific operational elements not defined in general guidance were also incorporated, including harmonised baseline phenotyping, disease-specific endpoint menus, practical imaging and biomarker options. This framework turns fragmented guidance into a practical, auditable pre-FPI roadmap for stem cell trials in movement disorders. By combining a universal Core Gate with risk-proportionate modules, it aims to reduce protocol heterogeneity, improve cross-trial comparability, strengthen regulatory planning, and support safer, interpretable clinical translation.<\/jats:p>","DOI":"10.1177\/11795735261463495","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:16:13Z","timestamp":1784542573000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["A Translational Readiness Checklist for Stem-Cell\u2013Based Trials in Movement Disorders: A Practical Roadmap"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3322-1091","authenticated-orcid":false,"given":"Sahar","family":"Hemeda","sequence":"first","affiliation":[{"name":"University of P\u00e9cs"},{"name":"University of Khartoum"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f3zsef","family":"Janszky","sequence":"additional","affiliation":[{"name":"University of P\u00e9cs"},{"name":"HUN-REN-PTE Clinical Neuroscience MR Research Group, P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e1vid","family":"Pint\u00e9r","sequence":"additional","affiliation":[{"name":"University of P\u00e9cs"},{"name":"HUN-REN-PTE Clinical Neuroscience MR Research Group, P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"University of P\u00e9cs"},{"name":"HUN-REN-PTE Clinical Neuroscience MR Research Group, P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12757"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a033118"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2024.1498756"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2022.2029703"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-71779-1_1"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26497"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.571185"},{"key":"e_1_3_6_9_2","unstructured":"Johnson LA Vitek JL. Deep Brain Stimulation: Mechanisms of Action. Youmans and Winn Neurological Surgery. 1-4:748-760.e7. 60.e7. 8th Edition2023."},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","unstructured":"Rai SN Singh S Singh SK. Implication and Importance of Stem Cell Therapy in a Translational Model of Neurodegenerative Diseases. Neurodegenerative Diseases: Translational Models Mechanisms and Therapeutics 2024. 224-230. doi:10.1201\/9781032620442.","DOI":"10.1201\/9781032620442"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells10081992"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.798826"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.3727\/096368912X655145"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2025.115525"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2007.11.001"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-011-8219-8"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08700-0"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.70028"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2013.08.007"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08845-y"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28201"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23612"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007720"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.2174\/156720213804805936"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.3727\/096368916X694373"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.09.010"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-025-04703-w"},{"key":"e_1_3_6_28_2","unstructured":"A Phase II. Randomized Double-Blind Placebo-controlled Single-Center Study to Evaluate the Safety and Efficacy of Stemchymal (Allogeneic Adipose-derived Mesenchymal Stem Cells) Infusion for the Treatment of PolyQ Spinocerebellar Ataxia. 2024. [Internet]Available from: https:\/\/clinicaltrials.gov\/study\/NCT06397274"},{"key":"e_1_3_6_29_2","volume-title":"Multiple System Atrophy","year":"2021","unstructured":"Randomized Double-Blind Placebo-Controlled Adaptive Design Trial Of Intrathecally Administered Autologous Mesenchymal Stem Cells In Multiple System Atrophy [Internet]. 2021. Available from: https:\/\/clinicaltrials.gov\/study\/NCT05167721"},{"key":"e_1_3_6_30_2","unstructured":"Phase 1 Study To Assess the Safety and Tolerability of Human Embryonic Stem Cell-Derived Midbrain Dopamine Neuron Cell Therapy (MSK-DA01) For Advanced Parkinson's Disease. 2021. [Internet]Available from: https:\/\/clinicaltrials.gov\/study\/NCT04802733"},{"key":"e_1_3_6_31_2","unstructured":"STEM-PD Trial: A Multicentre Single Arm First in Human Dose-escalation Trial Investigating the Safety and Tolerability of Intraputamenal Transplantation of Human Embryonic Stem Cell Derived Dopaminergic Cells for Parkinson's Disease. STEM-PD Product). 2021. [Internet]Available from: https:\/\/clinicaltrials.gov\/study\/NCT05635409"},{"key":"e_1_3_6_32_2","unstructured":"A Phase I\/II. Open-Label Study to Assess the Safety and Efficacy of Striatum Transplantation of Human Embryonic Stem Cells-derived Neural Precursor Cells in Patients With Parkinson's Disease [Internet]. 2017. Available from: https:\/\/clinicaltrials.gov\/study\/NCT03119636"},{"key":"e_1_3_6_33_2","unstructured":"Intrathecal Autologous Mesenchymal Stem Cell Therapy in Multiple System Atrophy (MSA) - Effect of Dose and Natural History. 2014. [Internet]Available from: https:\/\/clinicaltrials.gov\/study\/NCT02315027"},{"key":"e_1_3_6_34_2","volume-title":"A Double-blind Placebo-controlled Randomized Clinical Trial of Autologous Mesenchymal Stem Cells in Patients With Multiple System Atrophy","year":"2009","unstructured":"A Double-blind Placebo-controlled Randomized Clinical Trial of Autologous Mesenchymal Stem Cells in Patients With Multiple System Atrophy. 2009. [Internet]Available from: https:\/\/clinicaltrials.gov\/study\/NCT00911365"},{"key":"e_1_3_6_35_2","unstructured":"Dose-Response Evaluation of the Investigational Product Cellavita HD After Intravenous Administration in Patients With Huntington's Disease. 2017. [Internet]Available from: https:\/\/clinicaltrials.gov\/study\/NCT03252535"},{"key":"e_1_3_6_36_2","unstructured":"Clinical Extension Study for Assessing the Safety and Efficacy of the Intravenous Administration of Cellavita-HD in Huntington's Disease Patients Who Participated in the ADORE-DH Study [Internet]. 2019. Available from: https:\/\/clinicaltrials.gov\/study\/NCT04219241"},{"key":"e_1_3_6_37_2","unstructured":"Treatment of Cerebellar Ataxia With Mesenchymal. Stem Cells. 2012. [Internet]Available from: https:\/\/clinicaltrials.gov\/study\/NCT01649687"},{"key":"e_1_3_6_38_2","doi-asserted-by":"crossref","first-page":"e081123","DOI":"10.1136\/bmj-2024-081123","article-title":"CONSORT 2025 statement: updated guideline for reporting randomised trials","volume":"389","author":"Hopewell S","year":"2025","unstructured":"Hopewell S, Chan A-W, Collins GS, et al. CONSORT 2025 statement: updated guideline for reporting randomised trials. BMJ. 2025;389:e081123.","journal-title":"BMJ"},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1201-365"},{"key":"e_1_3_6_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_3_6_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.09.001"},{"key":"e_1_3_6_42_2","unstructured":"Agency EM. Guideline on Human Cell-Based Medicinal Products. London: Committee for Medicinal Products for Human Use (CHMP). 2008. Report No.: EMEA\/CHMP\/410869\/2006."},{"key":"e_1_3_6_43_2","unstructured":"Agency EM. Guideline on Safety and Efficacy Follow-Up\u2013 Risk Management of Advanced Therapy Medicinal Products. In: London: Committee for Medicinal Products for Human Use (CHMP); 2008. Report No.: EMEA\/149995\/2008."},{"key":"e_1_3_6_44_2","volume-title":"ICH guideline E8 (R1) on general considerations for clinical studies","author":"Agency EM","year":"2021","unstructured":"Agency EM. ICH guideline E8 (R1) on general considerations for clinical studies. Amsterdam; 2021. Report No.: EMA\/CHMP\/ICH\/544570\/1998."},{"key":"e_1_3_6_45_2","volume-title":"ISSCR Guidelines for Stem Cell Research and Clinical Translation","author":"Research ISfSC","year":"2021","unstructured":"Research ISfSC. ISSCR Guidelines for Stem Cell Research and Clinical Translation; 20212021."},{"key":"e_1_3_6_46_2","volume-title":"Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy Products","author":"U.S. Department of Health and Human Services FaDA, Center for Biologics Evaluation and Research","year":"2013","unstructured":"U.S. Department of Health and Human Services FaDA, Center for Biologics Evaluation and Research. Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy Products; 20132013."},{"key":"e_1_3_6_47_2","unstructured":"Agency EM. ICH E9 (R1) addendum on estimands and sensitivity analysis in clinical trials to the guideline on statistical principles for clinical trials. 2020. Report No.: EMA\/CHMP\/ICH\/436221\/2017."},{"key":"e_1_3_6_48_2","unstructured":"Agency EM. ICH E6 (R3) Guideline on Good Clinical Practice (GCP). 2025. Step 5."},{"key":"e_1_3_6_49_2","volume-title":"Reflection paper on stem cell-based medicinal products","author":"Cat E","year":"2011","unstructured":"Cat E. Reflection paper on stem cell-based medicinal products. EMA\/CAT\/571134\/2009; 2011."}],"container-title":["Journal of Central Nervous System Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/11795735261463495","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/11795735261463495","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/11795735261463495","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T08:16:59Z","timestamp":1784708219000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/11795735261463495"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":48,"alternative-id":["10.1177\/11795735261463495"],"URL":"https:\/\/doi.org\/10.1177\/11795735261463495","relation":{},"ISSN":["1179-5735","1179-5735"],"issn-type":[{"value":"1179-5735","type":"print"},{"value":"1179-5735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"article-number":"11795735261463495"}}