A poster session from ACTRIMS 2020

P050: Beneficial Effects Of Autologous Mesenchymal Stem Cell (msc) Transplantation In Progressive Multiple Sclerosis: Report Of A Randomized Phase ii double blind trial

P. Petrou, I. Kassis, N. Levin, et al
Background: There is currently an unmet need for effective therapy in progressive multiple sclerosis(MS). Mesenchymal stem cells(MSCs) induce immune modulatory and neurotrophic effects.

Objectives: To evaluate the optimal way of administration, the safety and the clinical efficacy of MSC transplantation in patients with progressive MS.

Methods: A phase II randomized, placebo controlled, trial performed in a single referral center. 48 patients with active progressive MS and evidence of clinical activity during the previous year were enrolled. Patients were randomized into three groups and treated intrathecally (IT) or intravenously(IV) with autologous MSCs(1106/kg) or sham injections. After 6 months, half of the patients from the MSC-IT and MSC-IV groups were retreated with MSCs, and the other half, with sham injections. Patients initially assigned to sham treatment, were divided into two subgroups and treated with either MSC-IT or MSC-IV. The study duration was 14 months.Trial registration:NCT02166021.

Results: No serious, treatment related safety issues were detected. Significantly fewer patients experienced treatment failure in the MSC-IT and MSC-IV groups compared with those in the sham-treated group (6.7%, 9.7%, and 41.9%, respectively, p=0.0003 andp=0.0008). During the one-year follow up, 58.6% and 40.6% of patients treated with MSC-IT and MSC-IV, respectively, exhibited no evidence of disease activity(NEDA) compared with 9.7% in the sham-treated group (p<0.0001 and p<0.0048, respectively). MSC-IT transplantation induced additional benefits on the relapse rate, on the monthly changes of the T2 lesion load on MRI, and on the timed 25foot walking test, 9 hole peg test, optical coherence tomography, fMRI and cognitive tests.

Conclusions: Treatment with MSCs was well tolerated in progressive MS and induced beneficial effects regarding all primary endpoints. The IT administration was more efficacious, indicating that the observed effects may be mediated by neurotrophic/neuroprotective and central immunomodulatory mechanisms. A phase III trial is warranted to confirm these findings.