Safety and efficacy outcomes after intranasal administration of neural stem cells in cerebral palsy: a randomized phase 1/2 controlled trial

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

doi:10.1186/s13287-022-03234-y

Safety and efficacy outcomes after intranasal administration of neural stem cells in cerebral palsy: a randomized phase 1/2 controlled trial

Stem Cell Res Ther. 2023 Feb 9;14(1):23. doi: 10.1186/s13287-022-03234-y.

Authors

Zhongyue Lv^#^{1

2}, Ying Li^#^{1

2}, Yachen Wang^{1

2}, Fengyu Cong^{3

4}, Xiaoyan Li^{1

2}, Wanming Cui⁵, Chao Han^{1

2}, Yushan Wei⁶, Xiaojun Hong⁷, Yong Liu⁸, Luyi Ma⁹, Yang Jiao^{1

2

10}, Chi Zhang³, Huanjie Li¹¹, Mingyan Jin³, Liang Wang^{1

2}, Shiwei Ni^{1

2}, Jing Liu^{12

13}

Affiliations

¹ Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, Liaoning, China.
² Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, Liaoning, China.
³ School of Biomedical Engineering, Faculty of Electronic Information and Electrical Engineering, Dalian University of Technology, Dalian, Liaoning Province, China.
⁴ Faculty of Information Technology, University of Jyvaskyla, 40014, Jyvaskyla, Finland.
⁵ Department of Ent, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
⁶ Scientific Research Department, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
⁷ Neurophysiological Center, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
⁸ Department of Rehabilitation, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
⁹ Department of Pediatrics, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
¹⁰ Department of Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
¹¹ School of Biomedical Engineering, Dalian University of Technology, Dalian, Liaoning, China.
¹² Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, Liaoning, China. liujing@dmu.edu.cn.
¹³ Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, Liaoning, China. liujing@dmu.edu.cn.

^# Contributed equally.

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).

Keywords: Cerebral palsy; Clinical trials; Electroencephalogram; Functional brain network; Intranasal administration; Neural stem cells.

Publication types

Randomized Controlled Trial
Clinical Trial, Phase I
Research Support, Non-U.S. Gov't

MeSH terms

Activities of Daily Living
Administration, Intranasal
Brain / diagnostic imaging
Cerebral Palsy* / therapy
Child
Humans
Neural Stem Cells*

Associated data

ClinicalTrials.gov/NCT03005249