TY - JOUR
T1 - Human neural stem cell transplantation in ALS
T2 - Initial results from a phase I trial
AU - Mazzini, Letizia
AU - Gelati, Maurizio
AU - Profico, Daniela Celeste
AU - Sgaravizzi, Giada
AU - Projetti Pensi, Massimo
AU - Muzi, Gianmarco
AU - Ricciolini, Claudia
AU - Rota Nodari, Laura
AU - Carletti, Sandro
AU - Giorgi, Cesare
AU - Spera, Cristina
AU - Domenico, Frondizi
AU - Bersano, Enrica
AU - Petruzzelli, Francesco
AU - Cisari, Carlo
AU - Maglione, Annamaria
AU - Sarnelli, Maria Francesca
AU - Stecco, Alessandro
AU - Querin, Giorgia
AU - Masiero, Stefano
AU - Cantello, Roberto
AU - Ferrari, Daniela
AU - Zalfa, Cristina
AU - Binda, Elena
AU - Visioli, Alberto
AU - Trombetta, Domenico
AU - Novelli, Antonio
AU - Torres, Barbara
AU - Bernardini, Laura
AU - Carriero, Alessandro
AU - Prandi, Paolo
AU - Servo, Serena
AU - Cerino, Annalisa
AU - Cima, Valentina
AU - Gaiani, Alessandra
AU - Nasuelli, Nicola
AU - Massara, Maurilio
AU - Glass, Jonathan
AU - Sorarù, Gianni
AU - Boulis, Nicholas M.
AU - Vescovi, Angelo L.
N1 - Funding Information:
We thank all the patients participating in the trial and their families, the doctors, nurses, physical therapists at “Santa Maria”, “Maggiore della Carità” and “San Antonio” Hospitals and Stefania Moia for the organizative support. This trial was supported by the Revert Onlus Association and the Fondazione Cellule Staminali di Terni. The Fondazione Stefano Borgonovo also supported our research. Special thanks go to the "ASSICURAZIONI GENERALI" group, whose continued sponsorship was fundamental to the success of this research.
Publisher Copyright:
© 2015 Mazzini et al.
PY - 2015/12/12
Y1 - 2015/12/12
N2 - 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.
AB - 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.
KW - ALS
KW - Advanced therapies
KW - Cell therapy
KW - Foetal human neural stem cells
KW - Phase I trial
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U2 - 10.1186/s12967-014-0371-2
DO - 10.1186/s12967-014-0371-2
M3 - Article
C2 - 25889343
AN - SCOPUS:85016649701
SN - 1479-5876
VL - 13
JO - Journal of Translational Medicine
JF - Journal of Translational Medicine
IS - 1
M1 - 17
ER -