Literature DB >> 24018694

Intraspinal stem cell transplantation in amyotrophic lateral sclerosis: a phase I trial, cervical microinjection, and final surgical safety outcomes.

Jonathan Riley1, Jonathan Glass, Eva L Feldman, Meraida Polak, Jane Bordeau, Thais Federici, Karl Johe, Nicholas M Boulis.   

Abstract

BACKGROUND: The first US Food and Drug Administration approved clinical trial for a stem cell-based treatment of amyotrophic lateral sclerosis has now been completed.
OBJECTIVE: Primary aims assessed the safety of a direct microinjection-based technique and the toxicity of neural stem cell transplantation to the ventral horn of the cervical and thoracolumbar spinal cord. Results from thoracolumbar-only microinjection groups have been previously published. Cervical and cervical plus thoracolumbar microinjection group perioperative morbidity results are presented.
METHODS: Eighteen microinjection procedures (n = 12 thoracolumbar [T10/11], n = 6 cervical [C3-5]) delivered NSI-566RSC (Neuralstem, Inc), a human neural stem cell, to 15 patients in 5 cohorts. Each injection series comprised 5 injections of 10 μL at 4-mm intervals. The patients in group A (n = 6) were nonambulatory and received unilateral (n = 3) or bilateral (n = 3) thoracolumbar microinjections. The patients in groups B to E were ambulatory and received either unilateral (group B, n = 3) or bilateral (group C, n = 3) thoracolumbar microinjection. Group D and E patients received unilateral cervical (group D, n = 3) or cervical plus bilateral thoracolumbar microinjection (group E, n = 3).
RESULTS: Unilateral cervical (group D, n = 3) and cervical plus thoracolumbar (group E, n = 3) microinjections to the ventral horn have been completed in ambulatory patients. One patient developed a postoperative kyphotic deformity prompting completion of a laminoplasty in subsequent patients. Another required reoperation for wound dehiscence and infection. The solitary patient with bulbar amyotrophic lateral sclerosis required perioperative reintubation.
CONCLUSION: Delivery of a cellular payload to the cervical or thoracolumbar spinal cord was well tolerated by the spinal cord in this vulnerable population. This encouraging finding supports consideration of this delivery approach for neurodegenerative, oncologic, and traumatic spinal cord afflictions.

Entities:  

Mesh:

Year:  2014        PMID: 24018694     DOI: 10.1227/NEU.0000000000000156

Source DB:  PubMed          Journal:  Neurosurgery        ISSN: 0148-396X            Impact factor:   4.654


  34 in total

Review 1.  Intraspinal stem cell transplantation for amyotrophic lateral sclerosis.

Authors:  Kevin S Chen; Stacey A Sakowski; Eva L Feldman
Journal:  Ann Neurol       Date:  2016-02-12       Impact factor: 10.422

2.  Transplantation of spinal cord-derived neural stem cells for ALS: Analysis of phase 1 and 2 trials.

Authors:  Jonathan D Glass; Vicki S Hertzberg; Nicholas M Boulis; Jonathan Riley; Thais Federici; Meraida Polak; Jane Bordeau; Christina Fournier; Karl Johe; Tom Hazel; Merit Cudkowicz; Nazem Atassi; Lawrence F Borges; Seward B Rutkove; Jayna Duell; Parag G Patil; Stephen A Goutman; Eva L Feldman
Journal:  Neurology       Date:  2016-06-29       Impact factor: 9.910

Review 3.  Concise review: Stem cell therapies for amyotrophic lateral sclerosis: recent advances and prospects for the future.

Authors:  J Simon Lunn; Stacey A Sakowski; Eva L Feldman
Journal:  Stem Cells       Date:  2014-05       Impact factor: 6.277

Review 4.  Stem cell treatments for amyotrophic lateral sclerosis: a critical overview of early phase trials.

Authors:  Stephen A Goutman; Masha G Savelieff; Stacey A Sakowski; Eva L Feldman
Journal:  Expert Opin Investig Drugs       Date:  2019-06-12       Impact factor: 6.206

5.  Magnetic Resonance Imaging-Guided Transplantation of Neural Stem Cells into the Porcine Spinal Cord.

Authors:  Jason J Lamanna; Lindsey N Urquia; Carl V Hurtig; Juanmarco Gutierrez; Cody Anderson; Pete Piferi; Thais Federici; John N Oshinski; Nicholas M Boulis
Journal:  Stereotact Funct Neurosurg       Date:  2017-01-28       Impact factor: 1.875

6.  Amelioration of Penetrating Ballistic-Like Brain Injury Induced Cognitive Deficits after Neuronal Differentiation of Transplanted Human Neural Stem Cells.

Authors:  Markus S Spurlock; Aminul I Ahmed; Karla N Rivera; Shoji Yokobori; Stephanie W Lee; Pingdewinde N Sam; Deborah A Shear; Michael P Hefferan; Thomas G Hazel; Karl K Johe; Shyam Gajavelli; Frank C Tortella; Ross M Bullock
Journal:  J Neurotrauma       Date:  2017-03-23       Impact factor: 5.269

Review 7.  Recent Advances and the Future of Stem Cell Therapies in Amyotrophic Lateral Sclerosis.

Authors:  Stephen A Goutman; Kevin S Chen; Eva L Feldman
Journal:  Neurotherapeutics       Date:  2015-04       Impact factor: 7.620

Review 8.  Advances in stem cell therapy in Alzheimer's disease: a comprehensive clinical trial review.

Authors:  Nikolaos Karvelas; Samuel Bennett; Georgios Politis; Nikolaos-Iasonas Kouris; Christo Kole
Journal:  Stem Cell Investig       Date:  2022-02-21

Review 9.  Stem cells in the nervous system.

Authors:  Angel R Maldonado-Soto; Derek H Oakley; Hynek Wichterle; Joel Stein; Fiona K Doetsch; Christopher E Henderson
Journal:  Am J Phys Med Rehabil       Date:  2014-11       Impact factor: 2.159

Review 10.  Stem cell transplantation for amyotrophic lateral sclerosis: therapeutic potential and perspectives on clinical translation.

Authors:  Irene Faravelli; Giulietta Riboldi; Monica Nizzardo; Chiara Simone; Chiara Zanetta; Nereo Bresolin; Giacomo P Comi; Stefania Corti
Journal:  Cell Mol Life Sci       Date:  2014-04-04       Impact factor: 9.261

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