A randomized trial of mesenchymal stem cells in multiple system atrophy

• Published in: Annals of neurology Vol. 72; no. 1; pp. 32 - 40
• Main Authors: Lee, Phil Hyu, 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.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-07-2012; Wiley-Liss; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; Biological and medical sciences; Brain - metabolism; Brain - pathology; Cognition; Disease Progression; Double-Blind Method; Female; Humans; Infusions, Intra-Arterial; Male; Medical sciences; Mesenchymal Stem Cell Transplantation - methods; Middle Aged; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Multiple System Atrophy - metabolism; Multiple System Atrophy - pathology; Multiple System Atrophy - psychology; Multiple System Atrophy - therapy; Neurology; Neuropsychological Tests; Transplantation, Autologous; Treatment Outcome; Multiple system atrophy; Nervous system diseases; Stem cell
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.23612

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 × 107/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. ANN NEUROL 2012;72:32–40