title: Intraspinal stem cell transplantation in amyotrophic lateral sclerosis: a phase I trial, cervical microinjection, and final surgical safety outcomes.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: *Department of Neurosurgery, Emory University, Atlanta, Georgia; ‡Department of Neurology, Emory University, Atlanta, Georgia; §Department of Neurology, University of Michigan, Ann Arbor, Michigan; ¶Neuralstem, Inc, Rockville, Maryland.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Riley
authors.forename: Jonathan
authors.initials: J
authors.lastname: Glass
authors.forename: Eva L
authors.initials: EL
authors.lastname: Feldman
authors.forename: Meraida
authors.initials: M
authors.lastname: Polak
authors.forename: Jane
authors.initials: J
authors.lastname: Bordeau
authors.forename: Thais
authors.initials: T
authors.lastname: Federici
authors.forename: Karl
authors.initials: K
authors.lastname: Johe
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Boulis
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000601:surgery*; D005260:Female; D053686:Fetal Stem Cells / Q000637:transplantation*; D006801:Humans; D007278:Injections, Spinal; D008297:Male; D008845:Microinjections; D008875:Middle Aged; D058953:Neural Stem Cells / Q000637:transplantation*; D011183:Postoperative Complications / Q000473:pathology; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*