STOCKHOLM A new trial of autologous mesenchymal stem cells in progressive multiple sclerosis (MS) has shown encouraging results, with significant benefits vs placebo in several measures of disability.

The double-blind placebo-controlled phase 2 study described as "very pioneering" and "provocative" by outside commentators was presented at the recent 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2019.

Both intravenous and intrathecal administration of the stem cells showed beneficial clinical effects compared with placebo in terms of Expanded Disability Status Scale (EDSS) changes and several other functional outcomes, but the intrathecal route appeared superior to intravenous administration, reported Dimitrios Karussis, Hadassah University Hospital, Jerusalem, Israel.

Benefits were also noted mainly in the intrathecal group in relapse rates and several other secondary endpoints vs placebo, including timed 25-foot walk test, 9-hole peg test, several measures of cognitive function, and the rate of change of T2 lesion load on magnetic resonance imaging (MRI), as well as newer biomarkers including optimal coherence tomography, retinal nerve fiber layer thickness, and functional MRI motor network.

The study showed both intravenous and intrathecal administration of the cells appeared safe with no serious adverse events observed vs placebo.

"A phase 3 trial is warranted to confirm these findings," Karussis concluded.

Commenting for Medscape Medical News, Robert Fox, MD, Cleveland Clinic, co-chair of the session at which the study was presented, said the study was "provocative" as it showed "quite a robust change in disability trajectory and inflammatory markers despite only including a small number of patients."

"The data suggested a marked impact on these patients with progressive MS," Fox noted. "We've seen other stem cell trials but this is the one with the most provocative results which need to be understood further," he added.

Karussis explained that two small open-label clinical trials of mesenchymal stem cells have previously shown some indications of clinical benefits in MS and amyotrophic lateral sclerosis (ALS) patients in terms of stabilization of disability and some functional improvements.

"This third study is a double-blind, placebo-controlled trial to try and establish safety and the optimal route of administration intrathecal or intravenous injection in progressive MS," he said.

The study included 48 progressive MS patients with activity who had failed on at least one MS therapy and had an EDSS score of 3.0 to 6.5.

Mesenchymal stem cells were aspirated from the bone marrow of each patient, expanded in vivo, and then transplanted back into the patient intrathecally or intravenously at a dose of 1 million stem cells per kg body weight.

Each patient received two injections. For the first injection, 16 patients received stem cells by intrathecal injection, 16 received stem cells by intravenous injection, and 16 received placebo.

After 6 months the patients were crossed over and all patients who first got placebo were given stem cells (half by intrathecal and half by intravenous injection); those who first received stem cells were divided into two subgroups half received a second injection with the same route of administration as the first injection and the other half received placebo.

There was no major difference in baseline demographics in the three groups. Most patients had secondary progressive MS, with about 20% having primary progressive MS. The average EDSS at baseline was about 5.8 with an average progression over the previous year of around +0.7.

Efficacy results showed statistically significant benefits in patients receiving intrathecal stem cell injections vs placebo, with EDSS scores reducing by 0.2 vs an increase of 0.3 in the placebo group. The ambulation score improved by 0.8 points in the intrathecal stem cell group vs an increase of 1.3 with placebo.

The sum of functional scores improved by 3 points in the intrathecal stem cell group vs a worsening by 1 point in the placebo group. The mean number of relapses per patient were 0.06 in the intrathecal stem cell group vs 0.56 in the placebo group, and 94% of the intrathecal stem cell group was relapse free at the end of the study vs 53% of the placebo group.

There were also some smaller but significant improvements in some of the endpoints in the intravenous stem cell group vs placebo but not in the relapse rates, Karussis reported.

For the secondary endpoints patients receiving intrathecal stem cells had significant benefits in the 25-foot walk test, an improvement of 6% to 10% in walking speed vs a deterioration in the placebo group. The 9-hole peg test also showed positive results in the intrathecal stem cell group.

When comparing two treatments vs one treatment, only intrathecally treated patients showed superiority in each of the primary efficacy parameters compared with one treatment.

When asked how much of the effect was thought to be anti-inflammatory, Karussis replied that there appeared to be some dissociation between anti-inflammatory and other effects. "Gadolinium enhancing lesions were much less affected than some other disability parameters, including walking and functional MRI, which may indicate that the main effect was not immunomodulatory," he said.

Fox commented: "It will take a bit of diving into the data to understand how much might have been from an anti-inflammatory effect and how much was truly addressing the progressive facet of the disease."

"One concern was that the second 6 months of treatment patients who then went on placebo seemed to decline quite dramatically," Fox added. "So this begs the question of whether this is just a short-lived benefit and how often will these stem cells treatments need to be given."

Karussis and Fox have disclosed no relevant financial relationships.

35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2019: Abstract 157. Presented September 12, 2039.

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'Provocative' Results With Stem Cells in Progressive MS - Medscape