PMID- 33277427
OWN - NLM
STAT- MEDLINE
DCOM- 20211012
LR  - 20211012
IS  - 2332-7812 (Electronic)
IS  - 2332-7812 (Linking)
VI  - 8
IP  - 1
DP  - 2021 Jan
TI  - Mesenchymal stem cell-derived neural progenitors in progressive MS: Two-year 
      follow-up of a phase I study.
LID - 10.1212/NXI.0000000000000928 [doi]
LID - e928
AB  - 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.
CI  - Copyright (c) 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on 
      behalf of the American Academy of Neurology.
FAU - Harris, Violaine K
AU  - Harris VK
AUID- ORCID: 0000-0002-3057-3059
AD  - From the Tisch Multiple Sclerosis Research Center of New York.
FAU - Stark, James W
AU  - Stark JW
AD  - From the Tisch Multiple Sclerosis Research Center of New York.
FAU - Yang, Sophia
AU  - Yang S
AD  - From the Tisch Multiple Sclerosis Research Center of New York.
FAU - Zanker, Shayna
AU  - Zanker S
AD  - From the Tisch Multiple Sclerosis Research Center of New York.
FAU - Tuddenham, John
AU  - Tuddenham J
AD  - From the Tisch Multiple Sclerosis Research Center of New York.
FAU - Sadiq, Saud A
AU  - Sadiq SA
AD  - From the Tisch Multiple Sclerosis Research Center of New York. 
      ssadiq@tischms.org.
LA  - eng
SI  - ClinicalTrials.gov/NCT01933802
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201204
PL  - United States
TA  - Neurol Neuroimmunol Neuroinflamm
JT  - Neurology(R) neuroimmunology & neuroinflammation
JID - 101636388
RN  - 0 (CCL2 protein, human)
RN  - 0 (CXCL12 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (HGF protein, human)
RN  - 0 (Interleukin-8)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Chemokine CCL2/cerebrospinal fluid
MH  - Chemokine CXCL12/cerebrospinal fluid
MH  - Female
MH  - Follow-Up Studies
MH  - Hepatocyte Growth Factor/cerebrospinal fluid
MH  - Humans
MH  - Injections, Spinal
MH  - Interleukin-8/cerebrospinal fluid
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - Middle Aged
MH  - Multiple Sclerosis, Chronic Progressive/*therapy
MH  - Neural Stem Cells/*transplantation
MH  - Transplantation, Autologous
PMC - PMC7738177
EDAT- 2020/12/06 06:00
MHDA- 2021/10/13 06:00
PMCR- 2020/12/04
CRDT- 2020/12/05 05:27
PHST- 2020/07/16 00:00 [received]
PHST- 2020/10/14 00:00 [accepted]
PHST- 2020/12/05 05:27 [entrez]
PHST- 2020/12/06 06:00 [pubmed]
PHST- 2021/10/13 06:00 [medline]
PHST- 2020/12/04 00:00 [pmc-release]
AID - 8/1/e928 [pii]
AID - NEURIMMINFL2020033779 [pii]
AID - 10.1212/NXI.0000000000000928 [doi]
PST - epublish
SO  - Neurol Neuroimmunol Neuroinflamm. 2020 Dec 4;8(1):e928. doi: 
      10.1212/NXI.0000000000000928. Print 2021 Jan.