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

• Published in: Neurology : neuroimmunology & neuroinflammation Vol. 8; no. 1; p. e928
• Main Authors: Harris, Violaine K., Stark, James W., Yang, Sophia, Zanker, Shayna, Tuddenham, John, Sadiq, Saud A.
• Format: Journal Article
• Language: English
• Published: United States American Academy of Neurology 01.01.2021; Lippincott Williams & Wilkins
• ISSN: 2332-7812; 2332-7812
• DOI: 10.1212/NXI.0000000000000928

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. 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. 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. 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. 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. NCT01933802.