A randomized trial of mesenchymal stem cells in multiple system atrophy

philhyu Lee, Ji E. Lee, Han Soo Kim, Sook K. Song, Hye Sun Lee, Hyo Suk Nam, June Won Cheong, Yong Jeong, Hae Jeong Park, Dong Joon Kim, Chung Mo Nam, Jong Doo Lee, Hyun Ok Kim, Young H. Sohn

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Objective: Neuroprotective or regenerative strategies are invaluable in multiple system atrophy (MSA) due to its rapid progression with fatal prognosis. We evaluated the efficacy of autologous mesenchymal stem cells (MSC) in patients with MSA-cerebellar type (MSA-C). Methods: Thirty-three patients with probable MSA-C and baseline unified MSA rating scale (UMSARS) scores ranging from 30 to 50 were randomly assigned to receive MSC (4 × 10 7/injection) via intra-arterial and intravenous routes or placebo. The primary outcome was change in the total UMSARS scores from baseline throughout a 360-day follow-up period between groups. Secondary outcomes were changes in the UMSARS part II scores, cerebral glucose metabolism, gray matter density, and cognitive performance over a 360-day period. Results: The mixed model analysis of neurological deficits revealed a significant interaction effect between treatment group and time, suggesting that the MSC group had a smaller increase in total and part II UMSARS scores compared with the placebo group (p = 0.047 and p = 0.008, respectively). Cerebral glucose metabolism and gray matter density at 360 days relative to the baseline were more extensively decreased in the cerebellum and the cerebral cortical areas, along with greater deterioration of frontal cognition in the placebo group compared with the MSC group. We found no serious adverse effects that were directly related to MSC treatment. However, intra-arterial infusion resulted in small ischemic lesions on magnetic resonance imaging. Interpretation: MSC therapy could delay the progression of neurological deficits in patients with MSA-C, suggesting the potential of MSC therapy as a treatment candidate of MSA.

Original languageEnglish
Pages (from-to)32-40
Number of pages9
JournalAnnals of Neurology
Volume72
Issue number1
DOIs
Publication statusPublished - 2012 Jul 1

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Multiple System Atrophy
Mesenchymal Stromal Cells
Placebos
Cell- and Tissue-Based Therapy
Neurological Models
Intra-Arterial Injections
Glucose
Intra Arterial Infusions
Cerebellum
Cognition
Therapeutics
Magnetic Resonance Imaging

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Lee, P., Lee, J. E., Kim, H. S., Song, S. K., Lee, H. S., Nam, H. S., ... Sohn, Y. H. (2012). A randomized trial of mesenchymal stem cells in multiple system atrophy. Annals of Neurology, 72(1), 32-40. https://doi.org/10.1002/ana.23612
Lee, philhyu ; Lee, Ji E. ; Kim, Han Soo ; Song, Sook K. ; Lee, Hye Sun ; Nam, Hyo Suk ; Cheong, June Won ; Jeong, Yong ; Park, Hae Jeong ; Kim, Dong Joon ; Nam, Chung Mo ; Lee, Jong Doo ; Kim, Hyun Ok ; Sohn, Young H. / A randomized trial of mesenchymal stem cells in multiple system atrophy. In: Annals of Neurology. 2012 ; Vol. 72, No. 1. pp. 32-40.
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abstract = "Objective: Neuroprotective or regenerative strategies are invaluable in multiple system atrophy (MSA) due to its rapid progression with fatal prognosis. We evaluated the efficacy of autologous mesenchymal stem cells (MSC) in patients with MSA-cerebellar type (MSA-C). Methods: Thirty-three patients with probable MSA-C and baseline unified MSA rating scale (UMSARS) scores ranging from 30 to 50 were randomly assigned to receive MSC (4 × 10 7/injection) via intra-arterial and intravenous routes or placebo. The primary outcome was change in the total UMSARS scores from baseline throughout a 360-day follow-up period between groups. Secondary outcomes were changes in the UMSARS part II scores, cerebral glucose metabolism, gray matter density, and cognitive performance over a 360-day period. Results: The mixed model analysis of neurological deficits revealed a significant interaction effect between treatment group and time, suggesting that the MSC group had a smaller increase in total and part II UMSARS scores compared with the placebo group (p = 0.047 and p = 0.008, respectively). Cerebral glucose metabolism and gray matter density at 360 days relative to the baseline were more extensively decreased in the cerebellum and the cerebral cortical areas, along with greater deterioration of frontal cognition in the placebo group compared with the MSC group. We found no serious adverse effects that were directly related to MSC treatment. However, intra-arterial infusion resulted in small ischemic lesions on magnetic resonance imaging. Interpretation: MSC therapy could delay the progression of neurological deficits in patients with MSA-C, suggesting the potential of MSC therapy as a treatment candidate of MSA.",
author = "philhyu Lee and Lee, {Ji E.} and Kim, {Han Soo} and Song, {Sook K.} and Lee, {Hye Sun} and Nam, {Hyo Suk} and Cheong, {June Won} and Yong Jeong and Park, {Hae Jeong} and Kim, {Dong Joon} and Nam, {Chung Mo} and Lee, {Jong Doo} and Kim, {Hyun Ok} and Sohn, {Young H.}",
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Lee, P, Lee, JE, Kim, HS, Song, SK, Lee, HS, Nam, HS, Cheong, JW, Jeong, Y, Park, HJ, Kim, DJ, Nam, CM, Lee, JD, Kim, HO & Sohn, YH 2012, 'A randomized trial of mesenchymal stem cells in multiple system atrophy', Annals of Neurology, vol. 72, no. 1, pp. 32-40. https://doi.org/10.1002/ana.23612

A randomized trial of mesenchymal stem cells in multiple system atrophy. / Lee, philhyu; Lee, Ji E.; Kim, Han Soo; Song, Sook K.; Lee, Hye Sun; Nam, Hyo Suk; Cheong, June Won; Jeong, Yong; Park, Hae Jeong; Kim, Dong Joon; Nam, Chung Mo; Lee, Jong Doo; Kim, Hyun Ok; Sohn, Young H.

In: Annals of Neurology, Vol. 72, No. 1, 01.07.2012, p. 32-40.

Research output: Contribution to journalArticle

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T1 - A randomized trial of mesenchymal stem cells in multiple system atrophy

AU - Lee, philhyu

AU - Lee, Ji E.

AU - Kim, Han Soo

AU - Song, Sook K.

AU - Lee, Hye Sun

AU - Nam, Hyo Suk

AU - Cheong, June Won

AU - Jeong, Yong

AU - Park, Hae Jeong

AU - Kim, Dong Joon

AU - Nam, Chung Mo

AU - Lee, Jong Doo

AU - Kim, Hyun Ok

AU - Sohn, Young H.

PY - 2012/7/1

Y1 - 2012/7/1

N2 - Objective: Neuroprotective or regenerative strategies are invaluable in multiple system atrophy (MSA) due to its rapid progression with fatal prognosis. We evaluated the efficacy of autologous mesenchymal stem cells (MSC) in patients with MSA-cerebellar type (MSA-C). Methods: Thirty-three patients with probable MSA-C and baseline unified MSA rating scale (UMSARS) scores ranging from 30 to 50 were randomly assigned to receive MSC (4 × 10 7/injection) via intra-arterial and intravenous routes or placebo. The primary outcome was change in the total UMSARS scores from baseline throughout a 360-day follow-up period between groups. Secondary outcomes were changes in the UMSARS part II scores, cerebral glucose metabolism, gray matter density, and cognitive performance over a 360-day period. Results: The mixed model analysis of neurological deficits revealed a significant interaction effect between treatment group and time, suggesting that the MSC group had a smaller increase in total and part II UMSARS scores compared with the placebo group (p = 0.047 and p = 0.008, respectively). Cerebral glucose metabolism and gray matter density at 360 days relative to the baseline were more extensively decreased in the cerebellum and the cerebral cortical areas, along with greater deterioration of frontal cognition in the placebo group compared with the MSC group. We found no serious adverse effects that were directly related to MSC treatment. However, intra-arterial infusion resulted in small ischemic lesions on magnetic resonance imaging. Interpretation: MSC therapy could delay the progression of neurological deficits in patients with MSA-C, suggesting the potential of MSC therapy as a treatment candidate of MSA.

AB - Objective: Neuroprotective or regenerative strategies are invaluable in multiple system atrophy (MSA) due to its rapid progression with fatal prognosis. We evaluated the efficacy of autologous mesenchymal stem cells (MSC) in patients with MSA-cerebellar type (MSA-C). Methods: Thirty-three patients with probable MSA-C and baseline unified MSA rating scale (UMSARS) scores ranging from 30 to 50 were randomly assigned to receive MSC (4 × 10 7/injection) via intra-arterial and intravenous routes or placebo. The primary outcome was change in the total UMSARS scores from baseline throughout a 360-day follow-up period between groups. Secondary outcomes were changes in the UMSARS part II scores, cerebral glucose metabolism, gray matter density, and cognitive performance over a 360-day period. Results: The mixed model analysis of neurological deficits revealed a significant interaction effect between treatment group and time, suggesting that the MSC group had a smaller increase in total and part II UMSARS scores compared with the placebo group (p = 0.047 and p = 0.008, respectively). Cerebral glucose metabolism and gray matter density at 360 days relative to the baseline were more extensively decreased in the cerebellum and the cerebral cortical areas, along with greater deterioration of frontal cognition in the placebo group compared with the MSC group. We found no serious adverse effects that were directly related to MSC treatment. However, intra-arterial infusion resulted in small ischemic lesions on magnetic resonance imaging. Interpretation: MSC therapy could delay the progression of neurological deficits in patients with MSA-C, suggesting the potential of MSC therapy as a treatment candidate of MSA.

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