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J Transl Med. 2015 Jan 27;13:17. doi: 10.1186/s12967-014-0371-2.

Human neural stem cell transplantation in ALS: initial results from a phase I trial.

Author information

1
Department of Neurology, Eastern Piedmont University, Maggiore della Carità Hospital, Corso Mazzini n. 18-28100, Novara, Italy. mazzini.l@libero.it.
2
Laboratorio Cellule Staminali, Cell Factory e Biobanca, Terni Hospital, via Tristano di Joannuccio 1, 05100, Terni, Italy. m.gelati@css-mendel.it.
3
IRCCS Casa Sollievo della Sofferenza, viale dei Cappuccini, 71013 San Giovanni Rotondo, Foggia, Italy. m.gelati@css-mendel.it.
4
Laboratorio Cellule Staminali, Cell Factory e Biobanca, Terni Hospital, via Tristano di Joannuccio 1, 05100, Terni, Italy. d.profico@css-mendel.it.
5
IRCCS Casa Sollievo della Sofferenza, viale dei Cappuccini, 71013 San Giovanni Rotondo, Foggia, Italy. d.profico@css-mendel.it.
6
Laboratorio Cellule Staminali, Cell Factory e Biobanca, Terni Hospital, via Tristano di Joannuccio 1, 05100, Terni, Italy. giada.sgaravizzi@gmail.com.
7
Laboratorio Cellule Staminali, Cell Factory e Biobanca, Terni Hospital, via Tristano di Joannuccio 1, 05100, Terni, Italy. massimo.ppensi@gmail.com.
8
IRCCS Casa Sollievo della Sofferenza, viale dei Cappuccini, 71013 San Giovanni Rotondo, Foggia, Italy. massimo.ppensi@gmail.com.
9
Laboratorio Cellule Staminali, Cell Factory e Biobanca, Terni Hospital, via Tristano di Joannuccio 1, 05100, Terni, Italy. gianmuzi@gmail.com.
10
Laboratorio Cellule Staminali, Cell Factory e Biobanca, Terni Hospital, via Tristano di Joannuccio 1, 05100, Terni, Italy. claudiaricciolini@libero.it.
11
IRCCS Casa Sollievo della Sofferenza, viale dei Cappuccini, 71013 San Giovanni Rotondo, Foggia, Italy. claudiaricciolini@libero.it.
12
IRCCS Casa Sollievo della Sofferenza, viale dei Cappuccini, 71013 San Giovanni Rotondo, Foggia, Italy. laura.rotanodari@unimib.it.
13
Biotechnology and Bioscience Department Bicocca University, Piazza della Scienza 2, 20126, Milan, Italy. laura.rotanodari@unimib.it.
14
Department of Neuroscience, "Santa Maria" Hospital, Terni via Tristano di Joannuccio 1, 05100, Terni, Italy. sandro.carletti@virgilio.it.
15
Department of Neuroscience, "Santa Maria" Hospital, Terni via Tristano di Joannuccio 1, 05100, Terni, Italy. giorgi.cesare@gmail.com.
16
Department of Neuroscience, "Santa Maria" Hospital, Terni via Tristano di Joannuccio 1, 05100, Terni, Italy. c.spera@aospterni.it.
17
Department of Neuroscience, "Santa Maria" Hospital, Terni via Tristano di Joannuccio 1, 05100, Terni, Italy. dofro@libero.it.
18
Department of Neurology, Eastern Piedmont University, Maggiore della Carità Hospital, Corso Mazzini n. 18-28100, Novara, Italy. enricabersano@gmail.com.
19
IRCCS Casa Sollievo della Sofferenza, viale dei Cappuccini, 71013 San Giovanni Rotondo, Foggia, Italy. f.petruzzelli@operapadrepio.it.
20
Department of Physical Therapy, Maggiore della Carità Hospital, Corso Mazzini n. 18-28100, Novara, Italy. cisari@tin.it.
21
IRCCS Casa Sollievo della Sofferenza, viale dei Cappuccini, 71013 San Giovanni Rotondo, Foggia, Italy. annamaria.maglione@libero.it.
22
Department of Neurology, Eastern Piedmont University, Maggiore della Carità Hospital, Corso Mazzini n. 18-28100, Novara, Italy. mf.sarnelli@tiscali.it.
23
Department of Diagnostic and Interventional Radiology, "Eastern Piedmont" University, "Maggiore della Carità" Hospital, Corso Mazzini n. 18-28100, Novara, Italy. a.stecco@libero.it.
24
Department of Neuroscience, University of Padova, Via Giustiniani, 2 - 35100, Padova, Italy. giorgia.querin@gmail.com.
25
Department of Neuroscience, University of Padova, Via Giustiniani, 2 - 35100, Padova, Italy. stef.masiero@unipd.it.
26
Department of Neurology, Eastern Piedmont University, Maggiore della Carità Hospital, Corso Mazzini n. 18-28100, Novara, Italy. roberto.cantello@med.unipmn.it.
27
Biotechnology and Bioscience Department Bicocca University, Piazza della Scienza 2, 20126, Milan, Italy. daniela.ferrari@unimib.it.
28
Biotechnology and Bioscience Department Bicocca University, Piazza della Scienza 2, 20126, Milan, Italy. zalfa@unimib.it.
29
IRCCS Casa Sollievo della Sofferenza, viale dei Cappuccini, 71013 San Giovanni Rotondo, Foggia, Italy. elena.binda@unimib.it.
30
Biotechnology and Bioscience Department Bicocca University, Piazza della Scienza 2, 20126, Milan, Italy. elena.binda@unimib.it.
31
Biotechnology and Bioscience Department Bicocca University, Piazza della Scienza 2, 20126, Milan, Italy. alberto.visioli@unimib.it.
32
IRCCS Casa Sollievo della Sofferenza, viale dei Cappuccini, 71013 San Giovanni Rotondo, Foggia, Italy. d.trombetta@operapadrepio.it.
33
IRCCS Casa Sollievo della Sofferenza, viale dei Cappuccini, 71013 San Giovanni Rotondo, Foggia, Italy. a.novelli@css-mendel.it.
34
IRCCS Casa Sollievo della Sofferenza, viale dei Cappuccini, 71013 San Giovanni Rotondo, Foggia, Italy. b.torres@css-mendel.it.
35
IRCCS Casa Sollievo della Sofferenza, viale dei Cappuccini, 71013 San Giovanni Rotondo, Foggia, Italy. l.benardini@css-mendel.it.
36
Department of Diagnostic and Interventional Radiology, "Eastern Piedmont" University, "Maggiore della Carità" Hospital, Corso Mazzini n. 18-28100, Novara, Italy. profcarriero@virgilio.it.
37
Department of Neurology, Eastern Piedmont University, Maggiore della Carità Hospital, Corso Mazzini n. 18-28100, Novara, Italy. p.prandi@hotmail.it.
38
Department of Neurology, Eastern Piedmont University, Maggiore della Carità Hospital, Corso Mazzini n. 18-28100, Novara, Italy. serenaservo@gmail.com.
39
Department of Neurology, Eastern Piedmont University, Maggiore della Carità Hospital, Corso Mazzini n. 18-28100, Novara, Italy. annalisa_14@hotmail.com.
40
Department of Neuroscience, University of Padova, Via Giustiniani, 2 - 35100, Padova, Italy. valentina.cima@unipd.it.
41
Department of Neuroscience, University of Padova, Via Giustiniani, 2 - 35100, Padova, Italy. alessandra.gaiani@virgilio.it.
42
Department of Neurology, Eastern Piedmont University, Maggiore della Carità Hospital, Corso Mazzini n. 18-28100, Novara, Italy. docnico@tiscali.it.
43
Department of Physical Therapy, Maggiore della Carità Hospital, Corso Mazzini n. 18-28100, Novara, Italy. mauriliomassara@gmail.com.
44
Department of Neurology Emory University, 201 Dowman Dr, Atlanta, GA, 30322, USA. jglas03@emory.edu.
45
Department of Neuroscience, University of Padova, Via Giustiniani, 2 - 35100, Padova, Italy. gianni.soraru@unipd.it.
46
Department of Neurosurgery Emory University, 201 Dowman Dr, Atlanta, GA, 30322, USA. nboulis@emory.edu.
47
Laboratorio Cellule Staminali, Cell Factory e Biobanca, Terni Hospital, via Tristano di Joannuccio 1, 05100, Terni, Italy. vescovi@tin.it.
48
IRCCS Casa Sollievo della Sofferenza, viale dei Cappuccini, 71013 San Giovanni Rotondo, Foggia, Italy. vescovi@tin.it.
49
Biotechnology and Bioscience Department Bicocca University, Piazza della Scienza 2, 20126, Milan, Italy. vescovi@tin.it.
50
Fondazione Cellule Staminali di Terni, Terni Hospital, via Tristano di Joannuccio 1, 05100, Terni, Italy. vescovi@tin.it.

Abstract

BACKGROUND:

We report the initial results from a phase I clinical trial for ALS. We transplanted GMP-grade, fetal human neural stem cells from natural in utero death (hNSCs) into the anterior horns of the spinal cord to test for the safety of both cells and neurosurgical procedures in these patients. The trial was approved by the Istituto Superiore di Sanità and the competent Ethics Committees and was monitored by an external Safety Board.

METHODS:

Six non-ambulatory patients were treated. Three of them received 3 unilateral hNSCs microinjections into the lumbar cord tract, while the remaining ones received bilateral (n = 3 + 3) microinjections. None manifested severe adverse events related to the treatment, even though nearly 5 times more cells were injected in the patients receiving bilateral implants and a much milder immune-suppression regimen was used as compared to previous trials.

RESULTS:

No increase of disease progression due to the treatment was observed for up to18 months after surgery. Rather, two patients showed a transitory improvement of the subscore ambulation on the ALS-FRS-R scale (from 1 to 2). A third patient showed improvement of the MRC score for tibialis anterior, which persisted for as long as 7 months. The latter and two additional patients refused PEG and invasive ventilation and died 8 months after surgery due to the progression of respiratory failure. The autopsies confirmed that this was related to the evolution of the disease.

CONCLUSIONS:

We describe a safe cell therapy approach that will allow for the treatment of larger pools of patients for later-phase ALS clinical trials, while warranting good reproducibility. These can now be carried out under more standardized conditions, based on a more homogenous repertoire of clinical grade hNSCs. The use of brain tissue from natural miscarriages eliminates the ethical concerns that may arise from the use of fetal material.

TRIAL REGISTRATION:

EudraCT:2009-014484-39 .

PMID:
25889343
PMCID:
PMC4359401
DOI:
10.1186/s12967-014-0371-2
[Indexed for MEDLINE]
Free PMC Article

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