Indications of neuroprotective effects in progressive multiple sclerosis following autologous mesenchymal stem cells (MSC) transplantation: report of a randomised phase IIb double blind trial
ECTRIMS Online Library. Petrou P. Sep 12, 2019; 279455; 157
Panayiota Petrou
Panayiota Petrou
Contributions
Abstract

Abstract: 157

Type: Scientific Session

Abstract Category: Therapy - Neuroprotection and Repair

P. Petrou1, I. Kassis1, N. Levin1, P. Friedemann2, O. Frederike Cosima2, M. Scheel2, M. Hallimi1, N. Yaghmour1, T. Ben Hur1, A. Ginzberg1, D. Karussis1

1Unit of Neuroimmunology and Multiple Sclerosis Center, Neurology department and The Agnes-Ginges Center for Neurogenetics, Hadassah University Hospital, Jerusalem, Ein-Kerem, Israel, 2NeuroCure Clinical Research Center, Charité University, Berlin, Germany

Background: Mesenchymal stem cells (MSC) induce immune-modulatory and neurotrophic effects and are safe when administered to patients with multiple sclerosis (MS) or amyotrophic lateral sclerosis (ALS). This study aimed to evaluate the safety and efficacy of transplantation of autologous MSC transplantation in active progressive MS.
Methods: This single-centre double-blind crossover trial enrolled 48 patients with progressive MS (EDSS range: 3.5-6.5, mean: 5.6±0.8). Patients were randomised into three groups and treated intrathecally (IT) or intravenously (IV) with autologous MSCs (1x106/Kg) or placebo. At 6-months, treatment groups were crossed over and patients re-treated with either MSC or placebo. During the 2-months run-in period and the 12-months after treatment, participants were followed using EDSS, 25-foot timed walking, 9-hole peg test, neurocognitive tests, quantitative magnetic resonance imaging (MRI), functional MRI, optic coherence tomography (OCT), visual evoked potentials(VEP), and dynamic visual tests.
Results: No serious, treatment-related adverse events were observed. One patient withdrew from the trial. Per-protocol analysis of the pre-determined primary endpoint showed that significantly fewer patients experienced treatment failure (increase in EDSS or deterioration in any functional system) in the MSC-IT and MSC-IV groups compared with the placebo-treated patients (6.7 %, 9.7 % and 48.4 %, respectively, p=0.0003, chi-square test, pooled data of the 6-month periods in both phases of the trial). Additionally, 58.6% of the patients treated with MSC-IT and 40.6% of those treated with MSC-IV, exhibited no evidence of disease activity (NEDA: no relapses, no EDSS progression, no new T2 activity, no gadolinium-enhancing lesions in MRI) for 6 months, compared with 9.7% in the placebo groups. Significant benefits were observed in monthly changes of T2 lesion load, 25-foot walking, 9-hole peg test, retinal nerve fiber layer OCT and in cognitive tests, in IT treated patients. A less significant effect was also observed in the MSC-IV group.
Conclusion: IT and IV administration of autologous MSCs was well-tolerated in progressive MS and induced robust benefits regarding all primary endpoints. IT administration was more efficacious, possibly indicating that not only peripheral immunomodulatory but also neuroprotective/neuroregenerative mechanisms are involved. A phase III trial is warranted to confirm these findings.
Disclosure: All authors have no conflict of interest related to this presented study.
All have received consultant fees for participation in advisory boards or for presentations/lectures by pharmaceutical companies, not related to the subject or the results of the trial

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