title: Transplantation of spinal cord-derived neural stem cells for ALS: Analysis of phase 1 and 2 trials.
abstract: OBJECTIVE
  To test the safety of spinal cord transplantation of human stem cells in patients with amyotrophic lateral sclerosis (ALS) with escalating doses and expansion of the trial to multiple clinical centers.
  
  
  METHODS
  This open-label trial included 15 participants at 3 academic centers divided into 5 treatment groups receiving increasing doses of stem cells by increasing numbers of cells/injection and increasing numbers of injections. All participants received bilateral injections into the cervical spinal cord (C3-C5). The final group received injections into both the lumbar (L2-L4) and cervical cord through 2 separate surgical procedures. Participants were assessed for adverse events and progression of disease, as measured by the ALS Functional Rating Scale-Revised, forced vital capacity, and quantitative measures of strength. Statistical analysis focused on the slopes of decline of these phase 2 trial participants alone or in combination with the phase 1 participants (previously reported), comparing these groups to 3 separate historical control groups.
  
  
  RESULTS
  Adverse events were mostly related to transient pain associated with surgery and to side effects of immunosuppressant medications. There was one incident of acute postoperative deterioration in neurologic function and another incident of a central pain syndrome. We could not discern differences in surgical outcomes between surgeons. Comparisons of the slopes of decline with the 3 separate historical control groups showed no differences in mean rates of progression.
  
  
  CONCLUSIONS
  Intraspinal transplantation of human spinal cord-derived neural stem cells can be safely accomplished at high doses, including successive lumbar and cervical procedures. The procedure can be expanded safely to multiple surgical centers.
  
  
  METHODS
  This study provides Class IV evidence that for patients with ALS, spinal cord transplantation of human stem cells can be safely accomplished and does not accelerate the progression of the disease. This study lacks the precision to exclude important benefit or safety issues.
authors.affiliation: From the Departments of Neurology (J.D.G., M.P., J.B., C.F.) and Neurosurgery (N.M.B., J.R., T.F.), Emory University School of Medicine, Atlanta; Center for Nursing Data Science (V.S.H.), Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Neuralstem, Inc. (K.J., T.H.), Germantown, MD; Department of Neurology, Neurological Clinical Research Institute (M.C., N.A.), and Department of Neurosurgery (L.F.B.), Massachusetts General Hospital, Boston; Department of Neurology (S.B.R.), Beth Israel Hospital, Boston, MA; and Departments of Neurosurgery (P.G.P.) and Neurology (J.D., P.G.P., S.A.G., E.L.F.), University of Michigan, Ann Arbor, MI. Jglas03@emory.edu.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Glass
authors.affiliation: From the Departments of Neurology (J.D.G., M.P., J.B., C.F.) and Neurosurgery (N.M.B., J.R., T.F.), Emory University School of Medicine, Atlanta; Center for Nursing Data Science (V.S.H.), Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Neuralstem, Inc. (K.J., T.H.), Germantown, MD; Department of Neurology, Neurological Clinical Research Institute (M.C., N.A.), and Department of Neurosurgery (L.F.B.), Massachusetts General Hospital, Boston; Department of Neurology (S.B.R.), Beth Israel Hospital, Boston, MA; and Departments of Neurosurgery (P.G.P.) and Neurology (J.D., P.G.P., S.A.G., E.L.F.), University of Michigan, Ann Arbor, MI.
authors.forename: Vicki S
authors.initials: VS
authors.lastname: Hertzberg
authors.affiliation: From the Departments of Neurology (J.D.G., M.P., J.B., C.F.) and Neurosurgery (N.M.B., J.R., T.F.), Emory University School of Medicine, Atlanta; Center for Nursing Data Science (V.S.H.), Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Neuralstem, Inc. (K.J., T.H.), Germantown, MD; Department of Neurology, Neurological Clinical Research Institute (M.C., N.A.), and Department of Neurosurgery (L.F.B.), Massachusetts General Hospital, Boston; Department of Neurology (S.B.R.), Beth Israel Hospital, Boston, MA; and Departments of Neurosurgery (P.G.P.) and Neurology (J.D., P.G.P., S.A.G., E.L.F.), University of Michigan, Ann Arbor, MI.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Boulis
authors.affiliation: From the Departments of Neurology (J.D.G., M.P., J.B., C.F.) and Neurosurgery (N.M.B., J.R., T.F.), Emory University School of Medicine, Atlanta; Center for Nursing Data Science (V.S.H.), Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Neuralstem, Inc. (K.J., T.H.), Germantown, MD; Department of Neurology, Neurological Clinical Research Institute (M.C., N.A.), and Department of Neurosurgery (L.F.B.), Massachusetts General Hospital, Boston; Department of Neurology (S.B.R.), Beth Israel Hospital, Boston, MA; and Departments of Neurosurgery (P.G.P.) and Neurology (J.D., P.G.P., S.A.G., E.L.F.), University of Michigan, Ann Arbor, MI.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Riley
authors.affiliation: From the Departments of Neurology (J.D.G., M.P., J.B., C.F.) and Neurosurgery (N.M.B., J.R., T.F.), Emory University School of Medicine, Atlanta; Center for Nursing Data Science (V.S.H.), Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Neuralstem, Inc. (K.J., T.H.), Germantown, MD; Department of Neurology, Neurological Clinical Research Institute (M.C., N.A.), and Department of Neurosurgery (L.F.B.), Massachusetts General Hospital, Boston; Department of Neurology (S.B.R.), Beth Israel Hospital, Boston, MA; and Departments of Neurosurgery (P.G.P.) and Neurology (J.D., P.G.P., S.A.G., E.L.F.), University of Michigan, Ann Arbor, MI.
authors.forename: Thais
authors.initials: T
authors.lastname: Federici
authors.affiliation: From the Departments of Neurology (J.D.G., M.P., J.B., C.F.) and Neurosurgery (N.M.B., J.R., T.F.), Emory University School of Medicine, Atlanta; Center for Nursing Data Science (V.S.H.), Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Neuralstem, Inc. (K.J., T.H.), Germantown, MD; Department of Neurology, Neurological Clinical Research Institute (M.C., N.A.), and Department of Neurosurgery (L.F.B.), Massachusetts General Hospital, Boston; Department of Neurology (S.B.R.), Beth Israel Hospital, Boston, MA; and Departments of Neurosurgery (P.G.P.) and Neurology (J.D., P.G.P., S.A.G., E.L.F.), University of Michigan, Ann Arbor, MI.
authors.forename: Meraida
authors.initials: M
authors.lastname: Polak
authors.affiliation: From the Departments of Neurology (J.D.G., M.P., J.B., C.F.) and Neurosurgery (N.M.B., J.R., T.F.), Emory University School of Medicine, Atlanta; Center for Nursing Data Science (V.S.H.), Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Neuralstem, Inc. (K.J., T.H.), Germantown, MD; Department of Neurology, Neurological Clinical Research Institute (M.C., N.A.), and Department of Neurosurgery (L.F.B.), Massachusetts General Hospital, Boston; Department of Neurology (S.B.R.), Beth Israel Hospital, Boston, MA; and Departments of Neurosurgery (P.G.P.) and Neurology (J.D., P.G.P., S.A.G., E.L.F.), University of Michigan, Ann Arbor, MI.
authors.forename: Jane
authors.initials: J
authors.lastname: Bordeau
authors.affiliation: From the Departments of Neurology (J.D.G., M.P., J.B., C.F.) and Neurosurgery (N.M.B., J.R., T.F.), Emory University School of Medicine, Atlanta; Center for Nursing Data Science (V.S.H.), Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Neuralstem, Inc. (K.J., T.H.), Germantown, MD; Department of Neurology, Neurological Clinical Research Institute (M.C., N.A.), and Department of Neurosurgery (L.F.B.), Massachusetts General Hospital, Boston; Department of Neurology (S.B.R.), Beth Israel Hospital, Boston, MA; and Departments of Neurosurgery (P.G.P.) and Neurology (J.D., P.G.P., S.A.G., E.L.F.), University of Michigan, Ann Arbor, MI.
authors.forename: Christina
authors.initials: C
authors.lastname: Fournier
authors.affiliation: From the Departments of Neurology (J.D.G., M.P., J.B., C.F.) and Neurosurgery (N.M.B., J.R., T.F.), Emory University School of Medicine, Atlanta; Center for Nursing Data Science (V.S.H.), Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Neuralstem, Inc. (K.J., T.H.), Germantown, MD; Department of Neurology, Neurological Clinical Research Institute (M.C., N.A.), and Department of Neurosurgery (L.F.B.), Massachusetts General Hospital, Boston; Department of Neurology (S.B.R.), Beth Israel Hospital, Boston, MA; and Departments of Neurosurgery (P.G.P.) and Neurology (J.D., P.G.P., S.A.G., E.L.F.), University of Michigan, Ann Arbor, MI.
authors.forename: Karl
authors.initials: K
authors.lastname: Johe
authors.affiliation: From the Departments of Neurology (J.D.G., M.P., J.B., C.F.) and Neurosurgery (N.M.B., J.R., T.F.), Emory University School of Medicine, Atlanta; Center for Nursing Data Science (V.S.H.), Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Neuralstem, Inc. (K.J., T.H.), Germantown, MD; Department of Neurology, Neurological Clinical Research Institute (M.C., N.A.), and Department of Neurosurgery (L.F.B.), Massachusetts General Hospital, Boston; Department of Neurology (S.B.R.), Beth Israel Hospital, Boston, MA; and Departments of Neurosurgery (P.G.P.) and Neurology (J.D., P.G.P., S.A.G., E.L.F.), University of Michigan, Ann Arbor, MI.
authors.forename: Tom
authors.initials: T
authors.lastname: Hazel
authors.affiliation: From the Departments of Neurology (J.D.G., M.P., J.B., C.F.) and Neurosurgery (N.M.B., J.R., T.F.), Emory University School of Medicine, Atlanta; Center for Nursing Data Science (V.S.H.), Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Neuralstem, Inc. (K.J., T.H.), Germantown, MD; Department of Neurology, Neurological Clinical Research Institute (M.C., N.A.), and Department of Neurosurgery (L.F.B.), Massachusetts General Hospital, Boston; Department of Neurology (S.B.R.), Beth Israel Hospital, Boston, MA; and Departments of Neurosurgery (P.G.P.) and Neurology (J.D., P.G.P., S.A.G., E.L.F.), University of Michigan, Ann Arbor, MI.
authors.forename: Merit
authors.initials: M
authors.lastname: Cudkowicz
authors.affiliation: From the Departments of Neurology (J.D.G., M.P., J.B., C.F.) and Neurosurgery (N.M.B., J.R., T.F.), Emory University School of Medicine, Atlanta; Center for Nursing Data Science (V.S.H.), Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Neuralstem, Inc. (K.J., T.H.), Germantown, MD; Department of Neurology, Neurological Clinical Research Institute (M.C., N.A.), and Department of Neurosurgery (L.F.B.), Massachusetts General Hospital, Boston; Department of Neurology (S.B.R.), Beth Israel Hospital, Boston, MA; and Departments of Neurosurgery (P.G.P.) and Neurology (J.D., P.G.P., S.A.G., E.L.F.), University of Michigan, Ann Arbor, MI.
authors.forename: Nazem
authors.initials: N
authors.lastname: Atassi
authors.affiliation: From the Departments of Neurology (J.D.G., M.P., J.B., C.F.) and Neurosurgery (N.M.B., J.R., T.F.), Emory University School of Medicine, Atlanta; Center for Nursing Data Science (V.S.H.), Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Neuralstem, Inc. (K.J., T.H.), Germantown, MD; Department of Neurology, Neurological Clinical Research Institute (M.C., N.A.), and Department of Neurosurgery (L.F.B.), Massachusetts General Hospital, Boston; Department of Neurology (S.B.R.), Beth Israel Hospital, Boston, MA; and Departments of Neurosurgery (P.G.P.) and Neurology (J.D., P.G.P., S.A.G., E.L.F.), University of Michigan, Ann Arbor, MI.
authors.forename: Lawrence F
authors.initials: LF
authors.lastname: Borges
authors.affiliation: From the Departments of Neurology (J.D.G., M.P., J.B., C.F.) and Neurosurgery (N.M.B., J.R., T.F.), Emory University School of Medicine, Atlanta; Center for Nursing Data Science (V.S.H.), Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Neuralstem, Inc. (K.J., T.H.), Germantown, MD; Department of Neurology, Neurological Clinical Research Institute (M.C., N.A.), and Department of Neurosurgery (L.F.B.), Massachusetts General Hospital, Boston; Department of Neurology (S.B.R.), Beth Israel Hospital, Boston, MA; and Departments of Neurosurgery (P.G.P.) and Neurology (J.D., P.G.P., S.A.G., E.L.F.), University of Michigan, Ann Arbor, MI.
authors.forename: Seward B
authors.initials: SB
authors.lastname: Rutkove
authors.affiliation: From the Departments of Neurology (J.D.G., M.P., J.B., C.F.) and Neurosurgery (N.M.B., J.R., T.F.), Emory University School of Medicine, Atlanta; Center for Nursing Data Science (V.S.H.), Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Neuralstem, Inc. (K.J., T.H.), Germantown, MD; Department of Neurology, Neurological Clinical Research Institute (M.C., N.A.), and Department of Neurosurgery (L.F.B.), Massachusetts General Hospital, Boston; Department of Neurology (S.B.R.), Beth Israel Hospital, Boston, MA; and Departments of Neurosurgery (P.G.P.) and Neurology (J.D., P.G.P., S.A.G., E.L.F.), University of Michigan, Ann Arbor, MI.
authors.forename: Jayna
authors.initials: J
authors.lastname: Duell
authors.affiliation: From the Departments of Neurology (J.D.G., M.P., J.B., C.F.) and Neurosurgery (N.M.B., J.R., T.F.), Emory University School of Medicine, Atlanta; Center for Nursing Data Science (V.S.H.), Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Neuralstem, Inc. (K.J., T.H.), Germantown, MD; Department of Neurology, Neurological Clinical Research Institute (M.C., N.A.), and Department of Neurosurgery (L.F.B.), Massachusetts General Hospital, Boston; Department of Neurology (S.B.R.), Beth Israel Hospital, Boston, MA; and Departments of Neurosurgery (P.G.P.) and Neurology (J.D., P.G.P., S.A.G., E.L.F.), University of Michigan, Ann Arbor, MI.
authors.forename: Parag G
authors.initials: PG
authors.lastname: Patil
authors.affiliation: From the Departments of Neurology (J.D.G., M.P., J.B., C.F.) and Neurosurgery (N.M.B., J.R., T.F.), Emory University School of Medicine, Atlanta; Center for Nursing Data Science (V.S.H.), Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Neuralstem, Inc. (K.J., T.H.), Germantown, MD; Department of Neurology, Neurological Clinical Research Institute (M.C., N.A.), and Department of Neurosurgery (L.F.B.), Massachusetts General Hospital, Boston; Department of Neurology (S.B.R.), Beth Israel Hospital, Boston, MA; and Departments of Neurosurgery (P.G.P.) and Neurology (J.D., P.G.P., S.A.G., E.L.F.), University of Michigan, Ann Arbor, MI.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Goutman
authors.affiliation: From the Departments of Neurology (J.D.G., M.P., J.B., C.F.) and Neurosurgery (N.M.B., J.R., T.F.), Emory University School of Medicine, Atlanta; Center for Nursing Data Science (V.S.H.), Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Neuralstem, Inc. (K.J., T.H.), Germantown, MD; Department of Neurology, Neurological Clinical Research Institute (M.C., N.A.), and Department of Neurosurgery (L.F.B.), Massachusetts General Hospital, Boston; Department of Neurology (S.B.R.), Beth Israel Hospital, Boston, MA; and Departments of Neurosurgery (P.G.P.) and Neurology (J.D., P.G.P., S.A.G., E.L.F.), University of Michigan, Ann Arbor, MI.
authors.forename: Eva L
authors.initials: EL
authors.lastname: Feldman
mesh_terms: D000328:Adult; D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000628:therapy*; D002574:Cervical Vertebrae; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D008161:Lumbosacral Region; D008297:Male; D008875:Middle Aged; D058953:Neural Stem Cells / Q000637:transplantation*; D013116:Spinal Cord / Q000601:surgery*; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents