title: Intraspinal neural stem cell transplantation in amyotrophic lateral sclerosis: phase 1 trial outcomes.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Neurology, University of Michigan, Ann Arbor, MI.
authors: Eva L
authors: EL
authors: Feldman
authors: Nicholas M
authors: NM
authors: Boulis
authors: Junguk
authors: J
authors: Hur
authors: Karl
authors: K
authors: Johe
authors: Seward B
authors: SB
authors: Rutkove
authors: Thais
authors: T
authors: Federici
authors: Meraida
authors: M
authors: Polak
authors: Jane
authors: J
authors: Bordeau
authors: Stacey A
authors: SA
authors: Sakowski
authors: Jonathan D
authors: JD
authors: Glass
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000628:therapy*; D002574:Cervical Vertebrae / Q000601:surgery; D005260:Female; D006801:Humans; D008159:Lumbar Vertebrae / Q000601:surgery; D008297:Male; D008875:Middle Aged; D058953:Neural Stem Cells / Q000637:transplantation*; D020127:Recovery of Function; D013116:Spinal Cord / Q000601:surgery*; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome