Journal Article

Autologous haematopoietic stem cell transplantation fails to stop demyelination and neurodegeneration in multiple sclerosis

Imke Metz, Claudia F. Lucchinetti, Harry Openshaw, Antonio Garcia-Merino, Hans Lassmann, Marc S. Freedman, Harold L. Atkins, Biagio Azzarelli, Oldrich J. Kolar and Wolfgang Brück

in Brain

Published on behalf of The Guarantors of Brain

Volume 130, issue 5, pages 1254-1262
Published in print May 2007 | ISSN: 0006-8950
Published online February 2007 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awl370
Autologous haematopoietic stem cell transplantation fails to stop demyelination and neurodegeneration in multiple sclerosis

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The present study analyses autopsy material from five multiple sclerosis patients who received autologous stem cell transplantation. A total of 53 white matter lesions were investigated using routine and immunohistochemical stainings to characterize the demyelinating activity, inflammatory infiltrates, acutely damaged axons and macrophages/microglial cells. We found evidence for ongoing active demyelination in all of the five patients. The inflammatory infiltrate within the lesions showed only very few T cells and CD8+ cytotoxic T cells dominated the T cell population. B cells and plasma cells were completely absent from the lesions. High numbers of acutely damaged axons were found in active lesion areas. Tissue injury was associated with activated macrophages/microglial cells. The present results indicate that ongoing demyelination and axonal degeneration exist despite pronounced immunosuppression. Our data parallel results from some of the clinical phase I/II studies showing continued clinical disease progression in multiple sclerosis patients with high expanded disability system scores despite autologous stem cell transplantation.

Keywords: multiple sclerosis; stem cell transplantation; demyelination; neurodegeneration

Journal Article.  4912 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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