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

on behalf of the ALS-NSCs Trial Study Group

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
JournalStem cells translational medicine
DOIs
Publication statusPublished - Jan 1 2019

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Spinal Injections
Clinical Trials, Phase I
Neural Stem Cells
Amyotrophic Lateral Sclerosis
Transplantation
Tracheotomy
Translational Medical Research
Microinjections
Therapeutic Uses
Prosencephalon
Disease Progression
Spinal Cord
Research Design
Stem Cells
Tissue Donors
Psychology
Safety
Cell Line
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

Results from Phase I Clinical Trial with Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis : A Long-Term Outcome. / on behalf of the ALS-NSCs Trial Study Group.

In: Stem cells translational medicine, 01.01.2019.

Research output: Contribution to journalArticle

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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.",
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AU - Mazzini, Letizia

AU - Gelati, Maurizio

AU - Profico, Daniela Celeste

AU - Sorarù, Gianni

AU - Ferrari, Daniela

AU - Copetti, Massimiliano

AU - Muzi, Gianmarco

AU - Ricciolini, Claudia

AU - Carletti, Sandro

AU - Giorgi, Cesare

AU - Spera, Cristina

AU - Frondizi, Domenico

AU - Masiero, Stefano

AU - Stecco, Alessandro

AU - Cisari, Carlo

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AU - Marchi, Fabiola De

AU - Sarnelli, Maria Francesca

AU - Querin, Giorgia

AU - Cantello, Roberto

AU - Petruzzelli, Francesco

AU - Maglione, Annamaria

AU - Zalfa, Cristina

AU - Binda, Elena

AU - Visioli, Alberto

AU - Trombetta, Domenico

AU - Torres, Barbara

AU - Bernardini, Laura

AU - Gaiani, Alessandra

AU - Massara, Maurilio

AU - Paolucci, Silvia

AU - Boulis, Nicholas M.

AU - Vescovi, Angelo L.

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