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Neurology. 2019 Jul 2;93(1):e77-e87. doi: 10.1212/WNL.0000000000007720. Epub 2019 May 31.

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

Author information

1
From 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.
2
From 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.

Abstract

OBJECTIVE:

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

METHODS:

Utilizing 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).

RESULTS:

Twenty-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, p = 0.004) with an apparent dose-dependent effect.

CONCLUSIONS:

Intrathecal 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.

PMID:
31152011
PMCID:
PMC6659003
[Available on 2020-07-02]
DOI:
10.1212/WNL.0000000000007720

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