Treatment of spinocerebellar ataxia with mesenchymal stem cells

A phase I/IIa clinical study

Yun An Tsai, Ren Shyan Liu, Jiing Feng Lirng, Bang Hung Yang, Chin Hao Chang, Yi Chen Wang, Yu Shan Wu, Jennifer Hui Chun Ho, Oscar K. Lee, Bing Wen Soong

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Ataxia is one of the most devastating symptoms of many neurodegenerative disorders. As of today, there is not any effective treatment to retard its progression. Mesenchymal stem cells (MSCs) have shown promise in treating neurodegenerative diseases. We hereby report the results of a phase I/IIa clinical study conducted in Taiwan to primarily evaluate the safety, tolerability, and, secondarily, the possible efficacy of intravenous administration of allogeneic adipose tissue-derived MSCs from healthy donors. Six patients with spinocerebellar ataxia type 3 and one with multiple system atrophy-cerebellar type were included in this open-label study with intravenous administration of 106 cells/kg body weight. The subjects were closely monitored for 1 year for safety (vital signs, complete blood counts, serum biochemical profiles, and urinalysis) and possible efficacy (scale for assessment and rating of ataxia and sensory organization testing scores, metabolite ratios on the brain magnetic resonance spectroscopy, and brain glucose metabolism of 18-fluorodeoxyglucose using positron emission tomography). No adverse events related to the injection of MSCs during the 1-year follow-up were observed. The intravenous administration of allogeneic MSCs seemed well tolerated. Upon study completion, all patients wished to continue treatment with the allogeneic MSCs. We conclude that allogeneic MSCs given by intravenous injection seems to be safe and tolerable in patients with spinocerebellar ataxia type 3, thus supporting advancement of the clinical development of allogeneic MSCs for the treatment of spinocerebellar ataxias (SCAs) in a randomized, double-blind, placebo-controlled phase II trials.

Original languageEnglish
Pages (from-to)503-512
Number of pages10
JournalCell Transplantation
Volume26
Issue number3
DOIs
Publication statusPublished - 2017

Fingerprint

Spinocerebellar Ataxias
Stem cells
Mesenchymal Stromal Cells
Machado-Joseph Disease
Intravenous Administration
Ataxia
Neurodegenerative Diseases
Therapeutics
Brain
Magnetic resonance spectroscopy
Neurodegenerative diseases
Multiple System Atrophy
Safety
Positron emission tomography
Urinalysis
Blood Cell Count
Vital Signs
Metabolites
Clinical Studies
Taiwan

Keywords

  • Allogeneic mesenchymal stem cells (MSCs)
  • Clinical trials
  • Gait disorders/ataxia
  • Spinocerebellar ataxias (SCAs)
  • Trinucleotide repeat diseases

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

Cite this

Tsai, Y. A., Liu, R. S., Lirng, J. F., Yang, B. H., Chang, C. H., Wang, Y. C., ... Soong, B. W. (2017). Treatment of spinocerebellar ataxia with mesenchymal stem cells: A phase I/IIa clinical study. Cell Transplantation, 26(3), 503-512. https://doi.org/10.3727/096368916X694373

Treatment of spinocerebellar ataxia with mesenchymal stem cells : A phase I/IIa clinical study. / Tsai, Yun An; Liu, Ren Shyan; Lirng, Jiing Feng; Yang, Bang Hung; Chang, Chin Hao; Wang, Yi Chen; Wu, Yu Shan; Ho, Jennifer Hui Chun; Lee, Oscar K.; Soong, Bing Wen.

In: Cell Transplantation, Vol. 26, No. 3, 2017, p. 503-512.

Research output: Contribution to journalArticle

Tsai, YA, Liu, RS, Lirng, JF, Yang, BH, Chang, CH, Wang, YC, Wu, YS, Ho, JHC, Lee, OK & Soong, BW 2017, 'Treatment of spinocerebellar ataxia with mesenchymal stem cells: A phase I/IIa clinical study', Cell Transplantation, vol. 26, no. 3, pp. 503-512. https://doi.org/10.3727/096368916X694373
Tsai, Yun An ; Liu, Ren Shyan ; Lirng, Jiing Feng ; Yang, Bang Hung ; Chang, Chin Hao ; Wang, Yi Chen ; Wu, Yu Shan ; Ho, Jennifer Hui Chun ; Lee, Oscar K. ; Soong, Bing Wen. / Treatment of spinocerebellar ataxia with mesenchymal stem cells : A phase I/IIa clinical study. In: Cell Transplantation. 2017 ; Vol. 26, No. 3. pp. 503-512.
@article{667012c0a79d4bada55c3b9f602a880a,
title = "Treatment of spinocerebellar ataxia with mesenchymal stem cells: A phase I/IIa clinical study",
abstract = "Ataxia is one of the most devastating symptoms of many neurodegenerative disorders. As of today, there is not any effective treatment to retard its progression. Mesenchymal stem cells (MSCs) have shown promise in treating neurodegenerative diseases. We hereby report the results of a phase I/IIa clinical study conducted in Taiwan to primarily evaluate the safety, tolerability, and, secondarily, the possible efficacy of intravenous administration of allogeneic adipose tissue-derived MSCs from healthy donors. Six patients with spinocerebellar ataxia type 3 and one with multiple system atrophy-cerebellar type were included in this open-label study with intravenous administration of 106 cells/kg body weight. The subjects were closely monitored for 1 year for safety (vital signs, complete blood counts, serum biochemical profiles, and urinalysis) and possible efficacy (scale for assessment and rating of ataxia and sensory organization testing scores, metabolite ratios on the brain magnetic resonance spectroscopy, and brain glucose metabolism of 18-fluorodeoxyglucose using positron emission tomography). No adverse events related to the injection of MSCs during the 1-year follow-up were observed. The intravenous administration of allogeneic MSCs seemed well tolerated. Upon study completion, all patients wished to continue treatment with the allogeneic MSCs. We conclude that allogeneic MSCs given by intravenous injection seems to be safe and tolerable in patients with spinocerebellar ataxia type 3, thus supporting advancement of the clinical development of allogeneic MSCs for the treatment of spinocerebellar ataxias (SCAs) in a randomized, double-blind, placebo-controlled phase II trials.",
keywords = "Allogeneic mesenchymal stem cells (MSCs), Clinical trials, Gait disorders/ataxia, Spinocerebellar ataxias (SCAs), Trinucleotide repeat diseases",
author = "Tsai, {Yun An} and Liu, {Ren Shyan} and Lirng, {Jiing Feng} and Yang, {Bang Hung} and Chang, {Chin Hao} and Wang, {Yi Chen} and Wu, {Yu Shan} and Ho, {Jennifer Hui Chun} and Lee, {Oscar K.} and Soong, {Bing Wen}",
year = "2017",
doi = "10.3727/096368916X694373",
language = "English",
volume = "26",
pages = "503--512",
journal = "Cell Transplantation",
issn = "0963-6897",
publisher = "Cognizant Communication Corporation",
number = "3",

}

TY - JOUR

T1 - Treatment of spinocerebellar ataxia with mesenchymal stem cells

T2 - A phase I/IIa clinical study

AU - Tsai, Yun An

AU - Liu, Ren Shyan

AU - Lirng, Jiing Feng

AU - Yang, Bang Hung

AU - Chang, Chin Hao

AU - Wang, Yi Chen

AU - Wu, Yu Shan

AU - Ho, Jennifer Hui Chun

AU - Lee, Oscar K.

AU - Soong, Bing Wen

PY - 2017

Y1 - 2017

N2 - Ataxia is one of the most devastating symptoms of many neurodegenerative disorders. As of today, there is not any effective treatment to retard its progression. Mesenchymal stem cells (MSCs) have shown promise in treating neurodegenerative diseases. We hereby report the results of a phase I/IIa clinical study conducted in Taiwan to primarily evaluate the safety, tolerability, and, secondarily, the possible efficacy of intravenous administration of allogeneic adipose tissue-derived MSCs from healthy donors. Six patients with spinocerebellar ataxia type 3 and one with multiple system atrophy-cerebellar type were included in this open-label study with intravenous administration of 106 cells/kg body weight. The subjects were closely monitored for 1 year for safety (vital signs, complete blood counts, serum biochemical profiles, and urinalysis) and possible efficacy (scale for assessment and rating of ataxia and sensory organization testing scores, metabolite ratios on the brain magnetic resonance spectroscopy, and brain glucose metabolism of 18-fluorodeoxyglucose using positron emission tomography). No adverse events related to the injection of MSCs during the 1-year follow-up were observed. The intravenous administration of allogeneic MSCs seemed well tolerated. Upon study completion, all patients wished to continue treatment with the allogeneic MSCs. We conclude that allogeneic MSCs given by intravenous injection seems to be safe and tolerable in patients with spinocerebellar ataxia type 3, thus supporting advancement of the clinical development of allogeneic MSCs for the treatment of spinocerebellar ataxias (SCAs) in a randomized, double-blind, placebo-controlled phase II trials.

AB - Ataxia is one of the most devastating symptoms of many neurodegenerative disorders. As of today, there is not any effective treatment to retard its progression. Mesenchymal stem cells (MSCs) have shown promise in treating neurodegenerative diseases. We hereby report the results of a phase I/IIa clinical study conducted in Taiwan to primarily evaluate the safety, tolerability, and, secondarily, the possible efficacy of intravenous administration of allogeneic adipose tissue-derived MSCs from healthy donors. Six patients with spinocerebellar ataxia type 3 and one with multiple system atrophy-cerebellar type were included in this open-label study with intravenous administration of 106 cells/kg body weight. The subjects were closely monitored for 1 year for safety (vital signs, complete blood counts, serum biochemical profiles, and urinalysis) and possible efficacy (scale for assessment and rating of ataxia and sensory organization testing scores, metabolite ratios on the brain magnetic resonance spectroscopy, and brain glucose metabolism of 18-fluorodeoxyglucose using positron emission tomography). No adverse events related to the injection of MSCs during the 1-year follow-up were observed. The intravenous administration of allogeneic MSCs seemed well tolerated. Upon study completion, all patients wished to continue treatment with the allogeneic MSCs. We conclude that allogeneic MSCs given by intravenous injection seems to be safe and tolerable in patients with spinocerebellar ataxia type 3, thus supporting advancement of the clinical development of allogeneic MSCs for the treatment of spinocerebellar ataxias (SCAs) in a randomized, double-blind, placebo-controlled phase II trials.

KW - Allogeneic mesenchymal stem cells (MSCs)

KW - Clinical trials

KW - Gait disorders/ataxia

KW - Spinocerebellar ataxias (SCAs)

KW - Trinucleotide repeat diseases

UR - http://www.scopus.com/inward/record.url?scp=85014742160&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85014742160&partnerID=8YFLogxK

U2 - 10.3727/096368916X694373

DO - 10.3727/096368916X694373

M3 - Article

VL - 26

SP - 503

EP - 512

JO - Cell Transplantation

JF - Cell Transplantation

SN - 0963-6897

IS - 3

ER -