Mesenchymal stem cell-derived neural progenitors in progressive MS: Two-year follow-up of a phase I study.

Autor:	Harris VK; From the Tisch Multiple Sclerosis Research Center of New York., Stark JW; From the Tisch Multiple Sclerosis Research Center of New York., Yang S; From the Tisch Multiple Sclerosis Research Center of New York., Zanker S; From the Tisch Multiple Sclerosis Research Center of New York., Tuddenham J; From the Tisch Multiple Sclerosis Research Center of New York., Sadiq SA; From the Tisch Multiple Sclerosis Research Center of New York. ssadiq@tischms.org.
Jazyk:	angličtina
Zdroj:	Neurology(R) neuroimmunology & neuroinflammation [Neurol Neuroimmunol Neuroinflamm] 2020 Dec 04; Vol. 8 (1). Date of Electronic Publication: 2020 Dec 04 (Print Publication: 2021).
DOI:	10.1212/NXI.0000000000000928
Abstrakt:	Objective: To determine the long-term safety and efficacy of repeated intrathecal (IT) administration of autologous mesenchymal stem cell-derived neural progenitors (MSC-NPs) in patients with progressive MS by evaluating subjects 2 years after treatment. Methods: Twenty subjects were enrolled as part of a phase I, open-label single-arm study of 3 IT injections of MSC-NPs spaced 3 months apart. Subjects were evaluated for adverse events and disability outcomes including the Expanded Disability Status Scale (EDSS) and the timed 25-foot walk (T25FW). Long-term evaluation was conducted 2 years after the third treatment. CSF was collected before and 3 months after treatment. Results: Eighteen of the 20 study participants completed the full 2-year follow-up protocol. There were no long-term adverse events associated with repeated IT-MSC-NP treatment. Seven subjects showed sustained improvement in EDSS after 2 years, although the degree of improvement was not maintained in 5 of the subjects. Three of the 10 ambulatory subjects showed sustained improvement in the T25FW after 2 years. CSF biomarker analysis revealed a decrease in C-C motif chemokine ligand 2 (CCL2) and an increase in interleukin 8, hepatocyte growth factor, and C-X-C motif chemokine ligand 12 (CXCL12) after treatment. Conclusions: Safety and efficacy of repeated IT-MSC-NP treatment was sustained for 2 years; however, the degree of disability reversal was not sustained in a subset of patients. CSF biomarkers altered in response to IT-MSC-NP treatment may reflect specific immunoregulatory and trophic mechanisms of therapeutic response in MS. Classification of Evidence: This study provides Class IV evidence that for patients with progressive MS, IT administration of MSC-NPs is safe and effective. The study is rated Class IV because of the absence of a non-IT-MSC-NP-treated control group. Clinicaltrialsgov Identifier: NCT01933802. (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
Databáze:	MEDLINE
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