Safety and efficacy outcomes after intranasal administration of neural stem cells in cerebral palsy: a randomized phase 1/2 controlled trial
Abstract Background Neural stem cells (NSCs) are believed to have the most therapeutic potential for neurological disorders because they can differentiate into various neurons and glial cells. This research evaluated the safety and efficacy of intranasal administration of NSCs in children with cereb...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-022-03234-y |
| _version_ | 1828035333095161856 |
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| author | Zhongyue Lv Ying Li Yachen Wang Fengyu Cong Xiaoyan Li Wanming Cui Chao Han Yushan Wei Xiaojun Hong Yong Liu Luyi Ma Yang Jiao Chi Zhang Huanjie Li Mingyan Jin Liang Wang Shiwei Ni Jing Liu |
| author_facet | Zhongyue Lv Ying Li Yachen Wang Fengyu Cong Xiaoyan Li Wanming Cui Chao Han Yushan Wei Xiaojun Hong Yong Liu Luyi Ma Yang Jiao Chi Zhang Huanjie Li Mingyan Jin Liang Wang Shiwei Ni Jing Liu |
| author_sort | Zhongyue Lv |
| collection | DOAJ |
| description | Abstract Background Neural stem cells (NSCs) are believed to have the most therapeutic potential for neurological disorders because they can differentiate into various neurons and glial cells. This research evaluated the safety and efficacy of intranasal administration of NSCs in children with cerebral palsy (CP). The functional brain network (FBN) analysis based on electroencephalogram (EEG) and voxel-based morphometry (VBM) analysis based on T1-weighted images were performed to evaluate functional and structural changes in the brain. Methods A total of 25 CP patients aged 3–12 years were randomly assigned to the treatment group (n = 15), which received an intranasal infusion of NSCs loaded with nasal patches and rehabilitation therapy, or the control group (n = 10) received rehabilitation therapy only. The primary endpoints were the safety (assessed by the incidence of adverse events (AEs), laboratory and imaging examinations) and the changes in the Gross Motor Function Measure-88 (GMFM-88), the Activities of Daily Living (ADL) scale, the Sleep Disturbance Scale for Children (SDSC), and some adapted scales. The secondary endpoints were the FBN and VBM analysis. Results There were only four AEs happened during the 24-month follow-up period. There was no significant difference in the laboratory examinations before and after treatment, and the magnetic resonance imaging showed no abnormal nasal and intracranial masses. Compared to the control group, patients in the treatment group showed apparent improvements in GMFM-88 and ADL 24 months after treatment. Compared with the baseline, the scale scores of the Fine Motor Function, Sociability, Life Adaptability, Expressive Ability, GMFM-88, and ADL increased significantly in the treatment group 24 months after treatment, while the SDSC score decreased considerably. Compared with baseline, the FBN analysis showed a substantial decrease in brain network energy, and the VBM analysis showed a significant increase in gray matter volume in the treatment group after NSCs treatment. Conclusions Our results showed that intranasal administration of NSCs was well-tolerated and potentially beneficial in children with CP. Trial registration: The study was registered in ClinicalTrials.gov (NCT03005249, registered 29 December 2016, https://www.clinicaltrials.gov/ct2/show/NCT03005249 ) and the Medical Research Registration Information System (CMR-20161129-1003). |
| first_indexed | 2024-04-10T15:46:23Z |
| format | Article |
| id | doaj.art-65f6acc0838f47e7ac3f47d89f1d5e06 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-10T15:46:23Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-65f6acc0838f47e7ac3f47d89f1d5e062023-02-12T12:05:58ZengBMCStem Cell Research & Therapy1757-65122023-02-0114111410.1186/s13287-022-03234-ySafety and efficacy outcomes after intranasal administration of neural stem cells in cerebral palsy: a randomized phase 1/2 controlled trialZhongyue Lv0Ying Li1Yachen Wang2Fengyu Cong3Xiaoyan Li4Wanming Cui5Chao Han6Yushan Wei7Xiaojun Hong8Yong Liu9Luyi Ma10Yang Jiao11Chi Zhang12Huanjie Li13Mingyan Jin14Liang Wang15Shiwei Ni16Jing Liu17Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical UniversityStem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical UniversityStem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical UniversitySchool of Biomedical Engineering, Faculty of Electronic Information and Electrical Engineering, Dalian University of TechnologyStem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical UniversityDepartment of Ent, The First Affiliated Hospital of Dalian Medical UniversityStem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical UniversityScientific Research Department, The First Affiliated Hospital of Dalian Medical UniversityNeurophysiological Center, The First Affiliated Hospital of Dalian Medical UniversityDepartment of Rehabilitation, The First Affiliated Hospital of Dalian Medical UniversityDepartment of Pediatrics, The First Affiliated Hospital of Dalian Medical UniversityStem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical UniversitySchool of Biomedical Engineering, Faculty of Electronic Information and Electrical Engineering, Dalian University of TechnologySchool of Biomedical Engineering, Dalian University of TechnologySchool of Biomedical Engineering, Faculty of Electronic Information and Electrical Engineering, Dalian University of TechnologyStem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical UniversityStem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical UniversityStem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical UniversityAbstract Background Neural stem cells (NSCs) are believed to have the most therapeutic potential for neurological disorders because they can differentiate into various neurons and glial cells. This research evaluated the safety and efficacy of intranasal administration of NSCs in children with cerebral palsy (CP). The functional brain network (FBN) analysis based on electroencephalogram (EEG) and voxel-based morphometry (VBM) analysis based on T1-weighted images were performed to evaluate functional and structural changes in the brain. Methods A total of 25 CP patients aged 3–12 years were randomly assigned to the treatment group (n = 15), which received an intranasal infusion of NSCs loaded with nasal patches and rehabilitation therapy, or the control group (n = 10) received rehabilitation therapy only. The primary endpoints were the safety (assessed by the incidence of adverse events (AEs), laboratory and imaging examinations) and the changes in the Gross Motor Function Measure-88 (GMFM-88), the Activities of Daily Living (ADL) scale, the Sleep Disturbance Scale for Children (SDSC), and some adapted scales. The secondary endpoints were the FBN and VBM analysis. Results There were only four AEs happened during the 24-month follow-up period. There was no significant difference in the laboratory examinations before and after treatment, and the magnetic resonance imaging showed no abnormal nasal and intracranial masses. Compared to the control group, patients in the treatment group showed apparent improvements in GMFM-88 and ADL 24 months after treatment. Compared with the baseline, the scale scores of the Fine Motor Function, Sociability, Life Adaptability, Expressive Ability, GMFM-88, and ADL increased significantly in the treatment group 24 months after treatment, while the SDSC score decreased considerably. Compared with baseline, the FBN analysis showed a substantial decrease in brain network energy, and the VBM analysis showed a significant increase in gray matter volume in the treatment group after NSCs treatment. Conclusions Our results showed that intranasal administration of NSCs was well-tolerated and potentially beneficial in children with CP. Trial registration: The study was registered in ClinicalTrials.gov (NCT03005249, registered 29 December 2016, https://www.clinicaltrials.gov/ct2/show/NCT03005249 ) and the Medical Research Registration Information System (CMR-20161129-1003).https://doi.org/10.1186/s13287-022-03234-yNeural stem cellsCerebral palsyIntranasal administrationElectroencephalogramClinical trialsFunctional brain network |
| spellingShingle | Zhongyue Lv Ying Li Yachen Wang Fengyu Cong Xiaoyan Li Wanming Cui Chao Han Yushan Wei Xiaojun Hong Yong Liu Luyi Ma Yang Jiao Chi Zhang Huanjie Li Mingyan Jin Liang Wang Shiwei Ni Jing Liu Safety and efficacy outcomes after intranasal administration of neural stem cells in cerebral palsy: a randomized phase 1/2 controlled trial Stem Cell Research & Therapy Neural stem cells Cerebral palsy Intranasal administration Electroencephalogram Clinical trials Functional brain network |
| title | Safety and efficacy outcomes after intranasal administration of neural stem cells in cerebral palsy: a randomized phase 1/2 controlled trial |
| title_full | Safety and efficacy outcomes after intranasal administration of neural stem cells in cerebral palsy: a randomized phase 1/2 controlled trial |
| title_fullStr | Safety and efficacy outcomes after intranasal administration of neural stem cells in cerebral palsy: a randomized phase 1/2 controlled trial |
| title_full_unstemmed | Safety and efficacy outcomes after intranasal administration of neural stem cells in cerebral palsy: a randomized phase 1/2 controlled trial |
| title_short | Safety and efficacy outcomes after intranasal administration of neural stem cells in cerebral palsy: a randomized phase 1/2 controlled trial |
| title_sort | safety and efficacy outcomes after intranasal administration of neural stem cells in cerebral palsy a randomized phase 1 2 controlled trial |
| topic | Neural stem cells Cerebral palsy Intranasal administration Electroencephalogram Clinical trials Functional brain network |
| url | https://doi.org/10.1186/s13287-022-03234-y |
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