PMID- 38016468
OWN - NLM
STAT- MEDLINE
DCOM- 20231216
LR  - 20240322
IS  - 1875-9777 (Electronic)
IS  - 1875-9777 (Linking)
VI  - 30
IP  - 12
DP  - 2023 Dec 7
TI  - Phase I clinical trial of intracerebroventricular transplantation of allogeneic 
      neural stem cells in people with progressive multiple sclerosis.
PG  - 1597-1609.e8
LID - S1934-5909(23)00393-4 [pii]
LID - 10.1016/j.stem.2023.11.001 [doi]
AB  - We report the analysis of 1 year of data from the first cohort of 15 patients 
      enrolled in an open-label, first-in-human, dose-escalation phase I study 
      (ClinicalTrials.gov: NCT03282760, EudraCT2015-004855-37) to determine the 
      feasibility, safety, and tolerability of the transplantation of allogeneic human 
      neural stem/progenitor cells (hNSCs) for the treatment of secondary progressive 
      multiple sclerosis. Participants were treated with hNSCs delivered via 
      intracerebroventricular injection in combination with an immunosuppressive 
      regimen. No treatment-related deaths nor serious adverse events (AEs) were 
      observed. All participants displayed stability of clinical and laboratory 
      outcomes, as well as lesion load and brain activity (MRI), compared with the 
      study entry. Longitudinal metabolomics and lipidomics of biological fluids 
      identified time- and dose-dependent responses with increased levels of 
      acyl-carnitines and fatty acids in the cerebrospinal fluid (CSF). The absence of 
      AEs and the stability of functional and structural outcomes are reassuring and 
      represent a milestone for the safe translation of stem cells into regenerative 
      medicines.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Leone, Maurizio A
AU  - Leone MA
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy.
FAU - Gelati, Maurizio
AU  - Gelati M
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy.
FAU - Profico, Daniela C
AU  - Profico DC
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy.
FAU - Gobbi, Claudio
AU  - Gobbi C
AD  - Multiple Sclerosis Centre (MSC), Department of Neurology, Neurocentre of Southern 
      Switzerland, EOC, 6900 Lugano, Switzerland; Faculty of Biomedical Sciences, 
      Universita della Svizzera Italiana (USI), 6900 Lugano, Switzerland.
FAU - Pravata, Emanuele
AU  - Pravata E
AD  - Multiple Sclerosis Centre (MSC), Department of Neurology, Neurocentre of Southern 
      Switzerland, EOC, 6900 Lugano, Switzerland; Faculty of Biomedical Sciences, 
      Universita della Svizzera Italiana (USI), 6900 Lugano, Switzerland; Department of 
      Neuroradiology, Neurocentre of Southern Switzerland, EOC, 6900 Lugano, 
      Switzerland.
FAU - Copetti, Massimiliano
AU  - Copetti M
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy.
FAU - Conti, Carlo
AU  - Conti C
AD  - Department of Biochemistry and Molecular Genetics, University of Colorado 
      Anschutz Medical Campus, 12801 East 17th A - L18-9118, Aurora, CO, USA.
FAU - Abate, Lucrezia
AU  - Abate L
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy.
FAU - Amoruso, Luigi
AU  - Amoruso L
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy.
FAU - Apollo, Francesco
AU  - Apollo F
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy.
FAU - Balzano, Rosario F
AU  - Balzano RF
AD  - Department of Neuroradiology, Neurocentre of Southern Switzerland, EOC, 6900 
      Lugano, Switzerland.
FAU - Bicchi, Ilaria
AU  - Bicchi I
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy; AOSP Santa Maria, via Tristano di Joannuccio 1, 05100 Terni, 
      Italy.
FAU - Carella, Massimo
AU  - Carella M
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy.
FAU - Ciampini, Alessandro
AU  - Ciampini A
AD  - AOSP Santa Maria, via Tristano di Joannuccio 1, 05100 Terni, Italy.
FAU - Colosimo, Carlo
AU  - Colosimo C
AD  - AOSP Santa Maria, via Tristano di Joannuccio 1, 05100 Terni, Italy.
FAU - Crociani, Paola
AU  - Crociani P
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy.
FAU - D'Aloisio, Giada
AU  - D'Aloisio G
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy.
FAU - Di Viesti, Pietro
AU  - Di Viesti P
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy.
FAU - Ferrari, Daniela
AU  - Ferrari D
AD  - Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza 
      della Scienza 2, 20126 Milan, Italy.
FAU - Fogli, Danilo
AU  - Fogli D
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy.
FAU - Fontana, Andrea
AU  - Fontana A
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy.
FAU - Frondizi, Domenico
AU  - Frondizi D
AD  - AOSP Santa Maria, via Tristano di Joannuccio 1, 05100 Terni, Italy.
FAU - Grespi, Valentina
AU  - Grespi V
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy; AOSP Santa Maria, via Tristano di Joannuccio 1, 05100 Terni, 
      Italy.
FAU - Kuhle, Jens
AU  - Kuhle J
AD  - Department of Neurology, University Hospital Basel, and University of Basel, 
      Basel, Switzerland.
FAU - Laborante, Antonio
AU  - Laborante A
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy.
FAU - Lombardi, Ivan
AU  - Lombardi I
AD  - Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza 
      della Scienza 2, 20126 Milan, Italy.
FAU - Muzi, Gianmarco
AU  - Muzi G
AD  - AOSP Santa Maria, via Tristano di Joannuccio 1, 05100 Terni, Italy.
FAU - Paci, Francesca
AU  - Paci F
AD  - AOSP Santa Maria, via Tristano di Joannuccio 1, 05100 Terni, Italy.
FAU - Placentino, Giuliana
AU  - Placentino G
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy.
FAU - Popolizio, Teresa
AU  - Popolizio T
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy.
FAU - Ricciolini, Claudia
AU  - Ricciolini C
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy; AOSP Santa Maria, via Tristano di Joannuccio 1, 05100 Terni, 
      Italy.
FAU - Sabatini, Simonetta
AU  - Sabatini S
AD  - AOSP Santa Maria, via Tristano di Joannuccio 1, 05100 Terni, Italy.
FAU - Silveri, Giada
AU  - Silveri G
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy.
FAU - Spera, Cristina
AU  - Spera C
AD  - AOSP Santa Maria, via Tristano di Joannuccio 1, 05100 Terni, Italy.
FAU - Stephenson, Daniel
AU  - Stephenson D
AD  - Department of Biochemistry and Molecular Genetics, University of Colorado 
      Anschutz Medical Campus, 12801 East 17th A - L18-9118, Aurora, CO, USA.
FAU - Stipa, Giuseppe
AU  - Stipa G
AD  - AOSP Santa Maria, via Tristano di Joannuccio 1, 05100 Terni, Italy.
FAU - Tinella, Elettra
AU  - Tinella E
AD  - AOSP Santa Maria, via Tristano di Joannuccio 1, 05100 Terni, Italy.
FAU - Zarrelli, Michele
AU  - Zarrelli M
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy.
FAU - Zecca, Chiara
AU  - Zecca C
AD  - Multiple Sclerosis Centre (MSC), Department of Neurology, Neurocentre of Southern 
      Switzerland, EOC, 6900 Lugano, Switzerland; Faculty of Biomedical Sciences, 
      Universita della Svizzera Italiana (USI), 6900 Lugano, Switzerland.
FAU - Ventura, Yendri
AU  - Ventura Y
AD  - Abu Dhabi Stem Cell Centre, Abu Dhabi, United Arab Emirates.
FAU - D'Alessandro, Angelo
AU  - D'Alessandro A
AD  - Department of Biochemistry and Molecular Genetics, University of Colorado 
      Anschutz Medical Campus, 12801 East 17th A - L18-9118, Aurora, CO, USA.
FAU - Peruzzotti-Jametti, Luca
AU  - Peruzzotti-Jametti L
AD  - Department of Clinical Neurosciences and NIHR Biomedical Research Centre, 
      University of Cambridge, CB2 0QQ Cambridge, UK; Department of Metabolism, 
      Digestion and Reproduction, Imperial College London, London, UK.
FAU - Pluchino, Stefano
AU  - Pluchino S
AD  - Department of Clinical Neurosciences and NIHR Biomedical Research Centre, 
      University of Cambridge, CB2 0QQ Cambridge, UK. Electronic address: 
      spp24@cam.ac.uk.
FAU - Vescovi, Angelo L
AU  - Vescovi AL
AD  - IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 
      71013 Foggia, Italy; Department of Biotechnology and Biosciences, University of 
      Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy. Electronic address: 
      angelo.vescovi@unimib.it.
LA  - eng
SI  - ClinicalTrials.gov/NCT03282760
GR  - P30 CA046934/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20231127
PL  - United States
TA  - Cell Stem Cell
JT  - Cell stem cell
JID - 101311472
SB  - IM
MH  - Humans
MH  - *Multiple Sclerosis, Chronic Progressive/drug therapy
MH  - *Multiple Sclerosis/therapy
MH  - Transplantation, Autologous
MH  - *Neural Stem Cells
MH  - *Hematopoietic Stem Cell Transplantation
OTO - NOTNLM
OT  - ATMPs
OT  - advanced cell therapy
OT  - clinical trial
OT  - human neural progenitor cells
OT  - intracerebroventricular injection
OT  - metabolomics
OT  - neural stem cells
OT  - progressive multiple sclerosis
COIS- Declaration of interests S.P. is founder, CSO, and shareholder (>5%) of CITC Ltd. 
      and Chair of the Scientific Advisory Board at ReNeuron plc.
EDAT- 2023/11/29 00:42
MHDA- 2023/12/17 09:42
CRDT- 2023/11/28 18:42
PHST- 2023/06/23 00:00 [received]
PHST- 2023/09/11 00:00 [revised]
PHST- 2023/11/01 00:00 [accepted]
PHST- 2023/12/17 09:42 [medline]
PHST- 2023/11/29 00:42 [pubmed]
PHST- 2023/11/28 18:42 [entrez]
AID - S1934-5909(23)00393-4 [pii]
AID - 10.1016/j.stem.2023.11.001 [doi]
PST - ppublish
SO  - Cell Stem Cell. 2023 Dec 7;30(12):1597-1609.e8. doi: 10.1016/j.stem.2023.11.001. 
      Epub 2023 Nov 27.