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

Letizia Mazzini, Maurizio Gelati, Daniela Celeste Profico, Giada Sgaravizzi, Massimo Projetti Pensi, Gianmarco Muzi, Claudia Ricciolini, Laura Rota Nodari, Sandro Carletti, Cesare Giorgi, Cristina Spera, Frondizi Domenico, Enrica Bersano, Francesco Petruzzelli, Carlo Cisari, Annamaria Maglione, Maria Francesca Sarnelli, Alessandro Stecco, Giorgia Querin, Stefano MasieroRoberto Cantello, Daniela Ferrari, Cristina Zalfa, Elena Binda, Alberto Visioli, Domenico Trombetta, Antonio Novelli, Barbara Torres, Laura Bernardini, Alessandro Carriero, Paolo Prandi, Serena Servo, Annalisa Cerino, Valentina Cima, Alessandra Gaiani, Nicola Nasuelli, Maurilio Massara, Jonathan Glass, Gianni Sorarù, Nicholas M. Boulis, Angelo L. Vescovi

Research output: Contribution to journalArticlepeer-review

137 Scopus citations


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.

Original languageEnglish (US)
Article number17
JournalJournal of Translational Medicine
Issue number1
StatePublished - Dec 12 2015


  • ALS
  • Advanced therapies
  • Cell therapy
  • Foetal human neural stem cells
  • Phase I trial

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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