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Author Notes:

Address correspondence to Dr Feldman, University of Michigan, 109 Zina Pitcher Place, 5017 AAT-BSRB, Ann Arbor, MI 48109. E-mail: efeldman@umich.edu

E.L.F., N.M.B., and J.D.G. designed the study.

K.J. provided critical study design input.

N.M.B., T.F., M.P., J.B., and J.D.G. contributed to data acquisition.

E.L.F., N.M.B., J.H., S.B.R., S.A.S., and J.D.G. were responsible for data analysis and interpretation.

E.L.F. and S.A.S. drafted the manuscript.

All authors critically edited the content of the article and approved the final version.

We thank the study participants and their families for their trust and dedication to advancing the field of ALS therapeutics; the trial Data Safety Monitoring Board, chaired by Dr Z. Simmons; Dr T. G. Hazel for providing the CGMP stem cells; L. Shaw for help with subject assessments; Dr M. Gearing for assistance with neuropathology; the staff of the Emory ALS Center; and J. Duell for assistance with table preparation.

See publication for full list of disclosures.

Subjects:

Research Funding:

This phase 1 study was funded by Neuralstem; the phase 2 study is funded by the NIH National Institute of Neurological Disorders and Stroke (R01 NS077982; J.D.G., E.L.F., N.M.B., S.B.R.), the ALS Association (E.L.F.), and Neuralstem.

Additional support for tissue and data analysis was provided by the NIH National Institute on Aging (5P50AG025688; J.D.G.) and the A. Alfred Taubman Medical Research Institute (E.L.F., N.M.B.).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Clinical Neurology
  • Neurosciences
  • Neurosciences & Neurology
  • SOD1 TRANSGENIC RATS
  • SPINAL-CORD
  • DIFFERENTIATION
  • TECHNOLOGY
  • DELIVERY
  • DISEASES
  • GRAFTS
  • FETAL

Intraspinal neural stem cell transplantation in amyotrophic lateral sclerosis: Phase 1 trial outcomes

Journal Title:

Annals of Neurology

Volume:

Volume 75, Number 3

Publisher:

, Pages 363-373

Type of Work:

Article | Final Publisher PDF

Abstract:

Objective The US Food and Drug Administration-approved trial, "A Phase 1, Open-Label, First-in-Human, Feasibility and Safety Study of Human Spinal Cord-Derived Neural Stem Cell Transplantation for the Treatment of Amyotrophic Lateral Sclerosis, Protocol Number: NS2008-1," is complete. Our overall objective was to assess the safety and feasibility of stem cell transplantation into lumbar and/or cervical spinal cord regions in amyotrophic lateral sclerosis (ALS) subjects. Methods Preliminary results have been reported on the initial trial cohort of 12 ALS subjects. Here, we describe the safety and functional outcome monitoring results for the final trial cohort, consisting of 6 ALS subjects receiving 5 unilateral cervical intraspinal neural stem cell injections. Three of these subjects previously received 10 total bilateral lumbar injections as part of the earlier trial cohort. All injections utilized a novel spinal-mounted stabilization and injection device to deliver 100,000 neural stem cells per injection, for a dosing range up to 1.5 million cells. Subject assessments included detailed pre- and postsurgical neurological outcome measures. Results The cervical injection procedure was well tolerated and disease progression did not accelerate in any subject, verifying the safety and feasibility of cervical and dual-targeting approaches. Analyses on outcome data revealed preliminary insight into potential windows of stem cell biological activity and identified clinical assessment measures that closely correlate with ALS Functional Rating Scale-Revised scores, a standard assessment for ALS clinical trials. Interpretation This is the first report of cervical and dual-targeted intraspinal transplantation of neural stem cells in ALS subjects. This approach is feasible and well-tolerated, supporting future trial phases examining therapeutic dosing and efficacy.

Copyright information:

© 2014 Child Neurology Society/American Neurological Association.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License (http://creativecommons.org/licenses/by-nc/3.0/).

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