Evidence map›Paper›PMID 27358335›Full record

Trial reportNeurology2016

Transplantation of spinal cord-derived neural stem cells for ALS: Analysis of phase 1 and 2 trials.

Jonathan D Glass, Vicki S Hertzberg, Nicholas M Boulis, Jonathan Riley, Thais Federici, Meraida Polak, Jane Bordeau, Christina Fournier, Karl Johe, Tom Hazel and 8 more

Erratum issuedOpen access · bronzeAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 83 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 4 pooled it
13.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

83 citing papers in PubMed, 4 syntheses or guidelines pooled it, 158 citations in OpenAlex.

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23 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 5 institutions in 1 country.

Jonathan D GlassFrom 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.
Vicki S HertzbergFrom 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.
Nicholas M BoulisFrom 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.
Jonathan RileyFrom 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.
Thais FedericiFrom 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.
Meraida PolakFrom 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.
Jane BordeauFrom 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.
Christina FournierFrom 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.
Karl JoheFrom 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.
Tom HazelFrom 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.
Merit CudkowiczFrom 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.
Nazem AtassiFrom 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.
Lawrence F BorgesFrom 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.
Seward B RutkoveFrom 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.
Jayna DuellFrom 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.
Parag G PatilFrom 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.
Stephen A GoutmanFrom 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.
Eva L FeldmanFrom 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.
Neural Signals (United States) · USEmory University · USMassachusetts General Hospital · USClinical Research Institute · USBeth Israel Deaconess Hospital · US

Funding

Phase 1b Trial of stem cells in ALSR01NS077982 · NINDS · EMORY UNIVERSITY · PI BOULIS, NICHOLAS M, FELDMAN, EVA LUCILLE · 2012 to 2015
$2.5M
NINDS NIH HHS R01 NS077982
6 · The paper itself

Abstract

objectiveTo 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.

methodsThis 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.

resultsAdverse 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.

conclusionsIntraspinal 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. CLASSIFICATION OF EVIDENCE: 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.

Indexed as

AdultAge of OnsetAmyotrophic Lateral SclerosisCervical VertebraeFemaleHumansImmunosuppressive AgentsLumbosacral RegionMaleMiddle AgedNeural Stem CellsSpinal CordStem Cell TransplantationTreatment OutcomeImmunosuppressive Agents

Identifiers

PMID27358335
PMCPMC4977116
OpenAlexW2462775742

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.