Evidence map›Paper›PMID 31152011›Full record

Trial reportNeurology2019

Intrathecal administration of autologous mesenchymal stem cells in multiple system atrophy.

Wolfgang Singer, Allan B Dietz, Anita D Zeller, Tonette L Gehrking, James D Schmelzer, Ann M Schmeichel, Jade A Gehrking, Mariana D Suarez, David M Sletten, Karla V Minota Pacheco and 11 more

Open access · bronzeAbstract readClinical Trial, Phase IClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
8.1field-weighted citation impact, top 2% 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

57 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Review
  6. Multiple system atrophy: cure and care.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Recent Advances in Clinical Trials in Multiple System Atrophy.Current neurology and neuroscience reports · 2024
    Review
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 1 institution in 1 country.

Wolfgang SingerFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN. singer.wolfgang@mayo.edu.
Allan B DietzFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.ORCID 0000-0003-3410-9621
Anita D ZellerFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.
Tonette L GehrkingFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.
James D SchmelzerFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.
Ann M SchmeichelFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.
Jade A GehrkingFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.
Mariana D SuarezFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.
David M SlettenFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.
Karla V Minota PachecoFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.
Elizabeth A CoonFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.
Paola SandroniFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.
Eduardo E BenarrochFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.
Robert D FealeyFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.
Joseph Y MatsumotoFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.
James H BowerFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.
Anhar HassanFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.
Andrew McKeonFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.
Anthony J WindebankFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.
Jay N MandrekarFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.
Phillip A LowFrom the Departments of Neurology (W.S., A.D.Z., T.L.G., J.D.S., A.M.S., J.A.G., M.D.S., D.M.S., K.V.M.P., E.A.C., P.S., E.E.B., R.D.F., J.Y.M., J.H.B., A.H., A.M., A.J.W., P.A.L.), Laboratory Medicine and Pathology (A.B.D.), and Biomedical Statistics and Informatics (J.N.M.), Mayo Clinic, Rochester, MN.
MACOM (United States) · US

Funding

Mayo Clinic Center for Translational Science ActivitiesUL1TR000135 · NCATS · MAYO CLINIC ROCHESTER · PI KHOSLA, SUNDEEP · 2012 to 2015
$41.2M
Studies on Diagnosis, Pathophysiology, and Treatment of Autonomic Failure in MSAP01NS044233 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MASLIAH, ELIEZER · 2003 to 2014
$12.4M
Training CoreU54NS065736 · NINDS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI KAUFMANN, HORACIO · 2009 to 2018
$11.6M
Synucleinopathies – Novel Targets in Early Diagnosis, Pathophysiology, and Therapeutic ApproachR01NS092625 · NINDS · MAYO CLINIC ROCHESTER · PI SINGER, WOLFGANG, VEMURI, PRASHANTHI · 2015 to 2025
$6.6M
Differential Approach to the Postural Tachycardia SyndromeK23NS075141 · NINDS · MAYO CLINIC ROCHESTER · PI SINGER, WOLFGANG · 2012 to 2016
$872k
Phase 1 Study of Autologous Mesenchymal Stem Cell in Multiple System AtrophyR01FD004789 · FDA · MAYO CLINIC ROCHESTER · PI LOW, PHILLIP A · 2014 to 2016
$600k
FDA HHS R01 FD004789NCATS NIH HHS UL1 TR000135NINDS NIH HHS K23 NS075141NINDS NIH HHS P01 NS044233NINDS NIH HHS R01 NS092625NINDS NIH HHS U54 NS065736
6 · The paper itself

Abstract

objectiveThis phase I/II study sought to explore intrathecal administration of mesenchymal stem cells (MSCs) as therapeutic approach to multiple system atrophy (MSA).

methodsUtilizing a dose-escalation design, we delivered between 10 and 200 million adipose-derived autologous MSCs intrathecally to patients with early MSA. Patients were closely followed with clinical, laboratory, and imaging surveillance. Primary endpoints were frequency and type of adverse events; key secondary endpoint was the rate of disease progression assessed by the Unified MSA Rating Scale (UMSARS).

resultsTwenty-four patients received treatment. There were no attributable serious adverse events, and injections were generally well-tolerated. At the highest dose tier, 3 of 4 patients developed low back/posterior leg pain, associated with thickening/enhancement of lumbar nerve roots. Although there were no associated neurologic deficits, we decided that dose-limiting toxicity was reached. A total of 6 of 12 patients in the medium dose tier developed similar, but milder and transient discomfort. Rate of progression (UMSARS total) was markedly lower compared to a matched historical control group (0.40 ± 0.59 vs 1.44 ± 1.42 points/month,

conclusionsIntrathecal MSC administration in MSA is safe and well-tolerated but can be associated with a painful implantation response at high doses. Compelling dose-dependent efficacy signals are the basis for a planned placebo-controlled trial. CLASSIFICATION OF EVIDENCE: This phase I/II study provides Class IV evidence that for patients with early MSA, intrathecal MSC administration is safe, may result in a painful implantation response at high doses, and is associated with dose-dependent efficacy signals.

Indexed as

Mesenchymal Stem Cell TransplantationDisease ProgressionFemaleFollow-Up StudiesHumansInjections, SpinalMaleMiddle AgedMultiple System AtrophyTreatment Outcome

Identifiers

PMID31152011
PMCPMC6659003
OpenAlexW2946930832

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.