title: Intraspinal stem cell transplantation in amyotrophic lateral sclerosis:  a phase I safety trial, technical note, and lumbar safety outcomes.
abstract: BACKGROUND
  No United States-based clinical trials have attempted delivery of biological therapies directly to the spinal cord for treatment of amyotrophic lateral sclerosis (ALS) because of the lack of a meaningful US Food and Drug Administration-authorized cell candidate and a validated delivery approach.
  
  
  OBJECTIVE
  To assess safety of delivery of a neural stem cell-based treatment into the upper lumbar segments of the ALS spinal cord in the first US Food and Drug Administration-authorized phase I trial.
  
  
  METHODS
  Each microinjection series comprised 5 injections (10 μL/injection) separated by 4 mm. Each injection deposited 100,000 neural stem cells derived from a fetal spinal cord. Twelve patients were treated with either unilateral or bilateral injections. Group A, nonambulatory patients, underwent unilateral (n = 3) or bilateral (n = 3) lumbar microinjections. Groups B and C were ambulatory (n = 3 each) and, respectively, received unilateral or bilateral injections. Patients are followed clinically and radiologically to assess potential toxicity of the procedure.
  
  
  RESULTS
  Twelve patients have received a transplant. There was one instance of transient intraoperative somatosensory-evoked potentials depression. In the immediate postoperative period, there was 1 episode of urinary retention requiring Foley catheter reinsertion. By discharge, none had a documented motor function decrement. Two patients required readmission and reoperation for cerebrospinal fluid leak or suprafascial wound dehiscence (n = 1 each). Two deaths occurred at 8 and 13 months postsurgery; neither was related to the surgical transplant.
  
  
  CONCLUSIONS
  Our experience in 12 patients supports the procedural safety of unilateral and bilateral intraspinal lumbar microinjection. Completion of this phase I safety trial is planned by proceeding to cervical and combined cervical + lumbar microinjections in ALS patients.
authors.affiliation: Department of Neurosurgery, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Riley
authors.forename: Thais
authors.initials: T
authors.lastname: Federici
authors.forename: Meraida
authors.initials: M
authors.lastname: Polak
authors.forename: Crystal
authors.initials: C
authors.lastname: Kelly
authors.forename: Jonathan
authors.initials: J
authors.lastname: Glass
authors.forename: Bethwel
authors.initials: B
authors.lastname: Raore
authors.forename: Jason
authors.initials: J
authors.lastname: Taub
authors.forename: Vita
authors.initials: V
authors.lastname: Kesner
authors.forename: Eva L
authors.initials: EL
authors.lastname: Feldman
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Boulis
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000175:diagnosis / Q000601:surgery*; D005260:Female; D006801:Humans; D007278:Injections, Spinal / Q000009:adverse effects; D008159:Lumbar Vertebrae / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000209:etiology* / Q000517:prevention & control; D033581:Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods*; D016896:Treatment Outcome