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Stem Cells Transl Med. 2019 May 18. doi: 10.1002/sctm.18-0154. [Epub ahead of print]

Results from Phase I Clinical Trial with Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis: A Long-Term Outcome.

Author information

1
Eastern Piedmont University, "Maggiore della Carità" Hospital, Dipartimento di Neurologia, Novara.
2
Laboratorio Cellule Staminali, Cell Factory e Biobanca, Terni Hospital, Italy.
3
Fondazione IRCCS Casa Sollievo della Sofferenza, Advanced Therapies Production Unit, San Giovanni Rotondo, Foggia, Italy.
4
Department of Neuroscience, University of Padua, Padua, Italy.
5
Biotechnology and Bioscience Department Bicocca University, Milan, Italy.
6
Fondazione IRCCS Casa Sollievo della Sofferenza, Biostatistic Unit, San Giovanni Rotondo, Foggia, Italy.
7
Department of Neurosurgery and Neuroscience, "Santa Maria" Hospital, Terni, Italy.
8
Department of Diagnostic and Interventional Radiology, "Eastern Piedmont" University, "Maggiore della Carità" Hospital, Novara.
9
Department of Physical Therapy, "Eastern Piedmont" University, "Maggiore della Carità" Hospital, Novara.
10
Fondazione IRCCS Casa Sollievo della Sofferenza, Obstetrics and Gynaecology Department, San Giovanni Rotondo, Foggia, Italy.
11
Fondazione IRCCS Casa Sollievo della Sofferenza, Cancer Stem Cells Unit, San Giovanni Rotondo, Foggia, Italy.
12
StemGen SpA, Milan, Italy.
13
Fondazione IRCCS Casa Sollievo della Sofferenza, Department of Oncology, San Giovanni Rotondo, Foggia, Italy.
14
Fondazione IRCCS Casa Sollievo della Sofferenza, Cytogenetics Unit, San Giovanni Rotondo, Foggia, Italy.
15
Department of Neurosurgery, Emory University, Atlanta, USA.

Abstract

The main objective of this phase I trial was to assess the feasibility and safety of microtransplanting human neural stem cell (hNSC) lines into the spinal cord of patients with amyotrophic lateral sclerosis (ALS). Eighteen patients with a definite diagnosis of ALS received microinjections of hNSCs into the gray matter tracts of the lumbar or cervical spinal cord. Patients were monitored before and after transplantation by clinical, psychological, neuroradiological, and neurophysiological assessment. For up to 60 months after surgery, none of the patients manifested severe adverse effects or increased disease progression because of the treatment. Eleven patients died, and two underwent tracheotomy as a result of the natural history of the disease. We detected a transitory decrease in progression of ALS Functional Rating Scale Revised, starting within the first month after surgery and up to 4 months after transplantation. Our results show that transplantation of hNSC is a safe procedure that causes no major deleterious effects over the short or long term. This study is the first example of medical transplantation of a highly standardized cell drug product, which can be reproducibly and stably expanded ex vivo, comprising hNSC that are not immortalized, and are derived from the forebrain of the same two donors throughout this entire study as well as across future trials. Our experimental design provides benefits in terms of enhancing both intra- and interstudy reproducibility and homogeneity. Given the potential therapeutic effects of the hNSCs, our observations support undertaking future phase II clinical studies in which increased cell dosages are studied in larger cohorts of patients. Stem Cells Translational Medicine 2019.

KEYWORDS:

Adult stem cells; Cellular therapy; Clinical trials; Fetal stem cells

PMID:
31104357
DOI:
10.1002/sctm.18-0154
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