MSC Therapy Shows Improvements in Open-Label Extension Trial for Patients With Multiple Sclerosis


Among 15 tested patients, who received at least 2 IT injections of the MSC therapy, improvements of between 5% and 18% in 25 feet walking were observed.

This article previously appeared on our sister site, NeurologyLive™.

A mesenchymal stem cell (MSC) therapy consisting of autologous MSCs has demonstrated significant beneficial effects on cognition and on objective biomarkers of neuroinflammation and neurodegeneration in patients with progressive multiple sclerosis (MS).1 The interim analysis, from an open-label extension trial, was presented at 2023 MSMilan, the 9th Joint ECTRIMS-ACTRIMS meeting, held October 11–13, in Milan, Italy.

Among 15 tested patients, who received at least 2 intrathecal (IT) injections of the MSC therapy, improvements of between 5% and 18% in 25 feet walking were observed. It was additionally noted that, after 3 MSC injections received over the course of 1 year, the average standard score of 4 cognitive tests taken by patients improved from 0.11 at baseline to 0.33. Furthermore, for 13 of 22 patients who received at least 1 MSC injection, improvements in Symbol Digit Modalities Test (SDMT) scores were observed. Improvements of more than 4 degrees in SDMT in 3 consecutive tests over the course of 1 year were seen in 6 of 17 treated patients were also noted.

The primary focus of this analysis was to evaluate the effect of repeated MSC transplantations on cognition in patients with progressive MS. Lead author, Petrou Panayiota, MD, senior neurologist, Unit of Neuroimmunology and Multiple Sclerosis Center and The Agnes-Ginges Center for Neurogenetics at Hadassah University Hospital in Jerusalem, Israel, and colleagues also looked at objective serum biomarkers of neuroinflammation and neurodegeneration, specifically neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), with the MSC therapy.

Patients with either secondary progressive MS or primary progressive MS who participated in the previous phase 2 double-blind clinical trial (NCT02166021) for the MSC therapy were eligible to participate in the study, and 48 were enrolled. At baseline, patients' conditions were assessed with the SDMT, California Verbal Learning Test, Brief Visuospatial Memory Test, and Controlled Oral Word Association Test. After the first administration of the therapy, patients' conditions were again assessed with these 4 tests at 4 to 5 time points. Simultaneously, Quanterix technology (SIMOA) was also used to measure the patients' serum NfL and GFAP levels.

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Among available data, 17 patients were treated with at least 2 intrathecal injections of MSC between 3 and 6 months apart, and 12 patients received 3 MSC injections. For treated patients, NfL levels reduced from a mean of 15.7 pmol/ml at baseline to 12.8 pmol/ml during the post-treatment year while GFAP levels also reduced from 191.4 pmol/ml at baseline to 155.4 pmol/ml.

In the previous double-blind randomized study conducted by Petrou and colleagues, IT injection of autologous bone marrow derived MSC showed robust clinical and radiological effects in patients with active and progressive MS.2 Enrolled patients had evidence of either clinical worsening or activity during the previous year between 2015 and 2018 and were randomized into 3 groups: IT or intravenous (IV) autologous MSCs (1×106/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 2 subgroups and treated with either MSC-IT or MSC-IV. After 14 months of the study, investigators did not observe any serious treatment-related safety adverse events. 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 = .0003 and P = .0008).

During the 1-year follow-up, 58.6% and 40.6% of patients treated with MSC-IT and MSC-IV, respectively, had no evidence of disease activity compared with 9.7% in the sham-treated group (P < .0001 and P < .0048, respectively). In addition, the 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 25-foot walking test, 9-hole peg test, optical coherence tomography, functional MRI and cognitive tests. Overall, treatment with MSCs was well-tolerated and induced short-term beneficial effects, especially in the patients with active disease. Notably, the IT administration was more efficacious than the intravenous in several parameters of the disease.

1. Panayiota P, Kassis I, Yaghmour NE, et al. effects of repeated autologous mesenchymal stem cells transplantation on cognition and serum biomarkers in progressive multiple sclerosis: interim analysis of an open label extension trial. Presented at: 2023 MSMilan; October 11-12; Milan, Italy. Abstract P377.
2. Petrou P, Kassis I, Levin N, et al. Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis. Brain. 2020;143(12):3574-3588. doi:10.1093/brain/awaa333
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