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Intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer’s disease dementia: a phase I clinical trial

BACKGROUNDS: Alzheimer’s disease is the most common cause of dementia, and currently, there is no disease-modifying treatment. Favorable functional outcomes and reduction of amyloid levels were observed following transplantation of mesenchymal stem cells (MSCs) in animal studies. OBJECTIVES: We cond...

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Autores principales: Kim, Hee Jin, Cho, Kyung Rae, Jang, Hyemin, Lee, Na Kyung, Jung, Young Hee, Kim, Jun Pyo, Lee, Jung Il, Chang, Jong Wook, Park, Seongbeom, Kim, Sung Tae, Moon, Seung Whan, Seo, Sang Won, Choi, Soo Jin, Na, Duk L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439008/
https://www.ncbi.nlm.nih.gov/pubmed/34521461
http://dx.doi.org/10.1186/s13195-021-00897-2
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author Kim, Hee Jin
Cho, Kyung Rae
Jang, Hyemin
Lee, Na Kyung
Jung, Young Hee
Kim, Jun Pyo
Lee, Jung Il
Chang, Jong Wook
Park, Seongbeom
Kim, Sung Tae
Moon, Seung Whan
Seo, Sang Won
Choi, Soo Jin
Na, Duk L.
author_facet Kim, Hee Jin
Cho, Kyung Rae
Jang, Hyemin
Lee, Na Kyung
Jung, Young Hee
Kim, Jun Pyo
Lee, Jung Il
Chang, Jong Wook
Park, Seongbeom
Kim, Sung Tae
Moon, Seung Whan
Seo, Sang Won
Choi, Soo Jin
Na, Duk L.
author_sort Kim, Hee Jin
collection PubMed
description BACKGROUNDS: Alzheimer’s disease is the most common cause of dementia, and currently, there is no disease-modifying treatment. Favorable functional outcomes and reduction of amyloid levels were observed following transplantation of mesenchymal stem cells (MSCs) in animal studies. OBJECTIVES: We conducted a phase I clinical trial in nine patients with mild-to-moderate Alzheimer’s disease dementia to evaluate the safety and dose-limiting toxicity of three repeated intracerebroventricular injections of human umbilical cord blood–derived MSCs (hUCB-MSCs). METHODS: We recruited nine mild-to-moderate Alzheimer’s disease dementia patients from Samsung Medical Center, Seoul, Republic of Korea. Four weeks prior to MSC administration, the Ommaya reservoir was implanted into the right lateral ventricle of the patients. Three patients received a low dose (1.0 × 10(7) cells/2 mL), and six patients received a high dose (3.0 × 10(7) cells/2 mL) of hUCB-MSCs. Three repeated injections of MSCs were performed (4-week intervals) in all nine patients. These patients were followed up to 12 weeks after the first hUCB-MSC injection and an additional 36 months in the extended observation study. RESULTS: After hUCB-MSC injection, the most common adverse event was fever (n = 9) followed by headache (n = 7), nausea (n = 5), and vomiting (n = 4), which all subsided within 36 h. There were three serious adverse events in two participants that were considered to have arisen from the investigational product. Fever in a low dose participant and nausea with vomiting in another low dose participant each required extended hospitalization by a day. There were no dose-limiting toxicities. Five participants completed the 36-month extended observation study, and no further serious adverse events were observed. CONCLUSIONS: Three repeated administrations of hUCB-MSCs into the lateral ventricle via an Ommaya reservoir were feasible, relatively and sufficiently safe, and well-tolerated. Currently, we are undergoing an extended follow-up study for those who participated in a phase IIa trial where upon completion, we hope to gain a deeper understanding of the clinical efficacy of MSC AD therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT02054208. Registered on 4 February 2014. ClinicalTrials.gov NCT03172117. Registered on 1 June 2017 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-021-00897-2.
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spelling pubmed-84390082021-09-14 Intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer’s disease dementia: a phase I clinical trial Kim, Hee Jin Cho, Kyung Rae Jang, Hyemin Lee, Na Kyung Jung, Young Hee Kim, Jun Pyo Lee, Jung Il Chang, Jong Wook Park, Seongbeom Kim, Sung Tae Moon, Seung Whan Seo, Sang Won Choi, Soo Jin Na, Duk L. Alzheimers Res Ther Research BACKGROUNDS: Alzheimer’s disease is the most common cause of dementia, and currently, there is no disease-modifying treatment. Favorable functional outcomes and reduction of amyloid levels were observed following transplantation of mesenchymal stem cells (MSCs) in animal studies. OBJECTIVES: We conducted a phase I clinical trial in nine patients with mild-to-moderate Alzheimer’s disease dementia to evaluate the safety and dose-limiting toxicity of three repeated intracerebroventricular injections of human umbilical cord blood–derived MSCs (hUCB-MSCs). METHODS: We recruited nine mild-to-moderate Alzheimer’s disease dementia patients from Samsung Medical Center, Seoul, Republic of Korea. Four weeks prior to MSC administration, the Ommaya reservoir was implanted into the right lateral ventricle of the patients. Three patients received a low dose (1.0 × 10(7) cells/2 mL), and six patients received a high dose (3.0 × 10(7) cells/2 mL) of hUCB-MSCs. Three repeated injections of MSCs were performed (4-week intervals) in all nine patients. These patients were followed up to 12 weeks after the first hUCB-MSC injection and an additional 36 months in the extended observation study. RESULTS: After hUCB-MSC injection, the most common adverse event was fever (n = 9) followed by headache (n = 7), nausea (n = 5), and vomiting (n = 4), which all subsided within 36 h. There were three serious adverse events in two participants that were considered to have arisen from the investigational product. Fever in a low dose participant and nausea with vomiting in another low dose participant each required extended hospitalization by a day. There were no dose-limiting toxicities. Five participants completed the 36-month extended observation study, and no further serious adverse events were observed. CONCLUSIONS: Three repeated administrations of hUCB-MSCs into the lateral ventricle via an Ommaya reservoir were feasible, relatively and sufficiently safe, and well-tolerated. Currently, we are undergoing an extended follow-up study for those who participated in a phase IIa trial where upon completion, we hope to gain a deeper understanding of the clinical efficacy of MSC AD therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT02054208. Registered on 4 February 2014. ClinicalTrials.gov NCT03172117. Registered on 1 June 2017 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-021-00897-2. BioMed Central 2021-09-14 /pmc/articles/PMC8439008/ /pubmed/34521461 http://dx.doi.org/10.1186/s13195-021-00897-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Kim, Hee Jin
Cho, Kyung Rae
Jang, Hyemin
Lee, Na Kyung
Jung, Young Hee
Kim, Jun Pyo
Lee, Jung Il
Chang, Jong Wook
Park, Seongbeom
Kim, Sung Tae
Moon, Seung Whan
Seo, Sang Won
Choi, Soo Jin
Na, Duk L.
Intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer’s disease dementia: a phase I clinical trial
title Intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer’s disease dementia: a phase I clinical trial
title_full Intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer’s disease dementia: a phase I clinical trial
title_fullStr Intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer’s disease dementia: a phase I clinical trial
title_full_unstemmed Intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer’s disease dementia: a phase I clinical trial
title_short Intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer’s disease dementia: a phase I clinical trial
title_sort intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with alzheimer’s disease dementia: a phase i clinical trial
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439008/
https://www.ncbi.nlm.nih.gov/pubmed/34521461
http://dx.doi.org/10.1186/s13195-021-00897-2
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