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Alzheimer’s disease (AD) is a neurodegenerative disease dominated by progressive cognitive dysfunction causing significant social, economic, and medical crises. Cell therapy has demonstrated favorable effects for AD. This pilot study examined the safety and neurorestorative effects of the olfactory ensheathing cell (OEC), olfactory neuron (ON), and Schwann cell (SC) on patients with AD. Seven patients with AD were enrolled in this two-center, randomized, double-blind, and placebo- controlled cell therapy study with a subsequent 12-month follow-up. We randomly assigned one or two participants in OEC, ON, and SC therapy or OEC combined with ON and placebo control. All enrolled patients were injected cells or medium into the olfactory sub-mucosa. They got an assessment of Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating before treatment and 1, 3, 6, 12 months after treatment. We performed MRI or CT scans before treatment and 12 months after treatment. After integrating the results from the three evaluation methods, all cell types showed better results than a placebo control. ON and SC seem to exhibit more vital potential neurorestorative ability to enhance or convert the neurological functions of patients with AD, and OEC may help AD patients keep neurological functions stable. In this pilot study, there was no adverse or side-effect event. The results of this study strongly suggest conducting a phase II clinical trial of ON, SC, and OEC therapy to prove their neurorestorative effect on patients with AD.


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A pilot study of clinical cell therapies in Alzheimer’s disease

Show Author's information Xiaoling Guo1( )Yunliang Wang2Yan Li1Yanqiu Liu2Ying Liu3Di Chen4Juan Xiao4Wenyong Gao4Bo Zhou1Yajun Liu2Ran Liu2Weidong Chen5Fei Liu6Deqiang Guo6Gensheng Mao3Hongyun Huang4( )
Neurological Department, The 981st Hospital of Chinese PLA, Chengde 067000, Hebei, China
Neurological Center, The 960th Hospital of Chinese PLA, Zibo 255300, Shandong, China
Institute of Neurorestoratology, The Third Medical Center of the General Hospital of the PLA, Beijing 100039, China
Beijing Hongtianji Neuroscience Academy, Beijing 100143, China
E.N.T. Department, The 981st Hospital of Chinese PLA, Chengde 067000, Hebei, China
E.N.T. Department, The 960th Hospital of Chinese PLA, Zibo 255300, Shandong, China

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease dominated by progressive cognitive dysfunction causing significant social, economic, and medical crises. Cell therapy has demonstrated favorable effects for AD. This pilot study examined the safety and neurorestorative effects of the olfactory ensheathing cell (OEC), olfactory neuron (ON), and Schwann cell (SC) on patients with AD. Seven patients with AD were enrolled in this two-center, randomized, double-blind, and placebo- controlled cell therapy study with a subsequent 12-month follow-up. We randomly assigned one or two participants in OEC, ON, and SC therapy or OEC combined with ON and placebo control. All enrolled patients were injected cells or medium into the olfactory sub-mucosa. They got an assessment of Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating before treatment and 1, 3, 6, 12 months after treatment. We performed MRI or CT scans before treatment and 12 months after treatment. After integrating the results from the three evaluation methods, all cell types showed better results than a placebo control. ON and SC seem to exhibit more vital potential neurorestorative ability to enhance or convert the neurological functions of patients with AD, and OEC may help AD patients keep neurological functions stable. In this pilot study, there was no adverse or side-effect event. The results of this study strongly suggest conducting a phase II clinical trial of ON, SC, and OEC therapy to prove their neurorestorative effect on patients with AD.

Keywords: Alzheimer’s disease, cell therapy, cognitive evaluation, neurorestorative effects, pilot study

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Received: 01 November 2021
Revised: 20 November 2021
Accepted: 22 November 2021
Published: 04 January 2022
Issue date: December 2021

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© The authors 2021

Acknowledgements

We thank Professor Lin Chen for his helpful suggestion for this study design.

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This article is published with open access at http://jnr.tsinghuajournals.com

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