AAN 2023: MSC-NP aids walking in advanced progressive MS patients

Use of the cell therapy MSC-NP failed to show a significant effect on overall disability scores among people with progressive forms of multiple sclerosis (MS), according to data from a Phase 2 clinical trial.

Results, however, indicated that MSC-NP improved walking ability for people with more advanced disease — those who need an aid to walk short distances. Patients treated with MSC-NP also often reported fewer bladder problems following treatment.

“The findings of this study suggest that stem cells could have major implications for treating MS and reversing patient disability even after significant progression,” Violaine Harris, PhD, a principal trial investigator at the Tisch MS Research Center of New York, said in a center press release.

They “are unprecedented in the realm of researching stem cells as a treatment pathway for progressive MS patients,” added Saud Sadiq, the Tisch Center’s director and chief research scientist. For a first time, “we have seen a regenerative treatment improve patient outcomes in multiple areas, providing strong evidence of the potential efficacy of stem cells in patients with significant and varying disabilities.”

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Sadiq presented findings from the trial at the American Academy of Neurology (AAN) 2023 Annual Meeting, in a talk titled, “Efficacy of Intrathecal Mesenchymal Stem Cell-Neural Progenitor Therapy in Progressive MS: Results from a Phase II Clinical Trial.” The work was funded in part by Biogen and the National MS Society.

MSC-NP is a treatment strategy that involves collecting mesenchymal stem cells, or MSCs, from a patient. These cells then are engineered in a laboratory to grow into neural progenitor cells, or NPs — a more specialized type of stem cell that’s able to grow into neurons (nerve cells) and other types of cells critical for nervous system health.

The engineered cells are injected into the patient’s nervous system through the spinal canal, called an intrathecal injection. Data from laboratory studies suggest that MSC-NP can reduce the activity of inflammatory cells in the nervous system that drive MS. Findings from an earlier Phase 1 trial (NCT01933802) suggested long-lasting functional improvements for some patients treated with MSC-NP.

Tisch then launched a Phase 2 clinical trial (NCT03355365) to evaluate the efficacy of MSC-NP in 54 people with primary progressive MS or secondary progressive disease. These types of MS are marked by symptoms that gradually worsen over time, independent of relapses, or sudden attacks of new or worsening symptoms.

All study participants had relatively advanced disability, with a score of at least three points on the Expanded Disability Status Scale (EDSS), although all still retained some ability to walk with an assistive device. They also had relatively stable disease, and had been living with MS for less than two decades in total.

Patients were randomly assigned to either MSC-NP or a placebo, given by intrathecal injection every two months for one year (a total of six injections). After the first year, participants crossed over — those initially given a placebo received a year of MSC-NP injections, while those initially treated with MSC-NP received a placebo in the second year.

Potential for MSC-NP to make ‘life-altering difference’ in progressive MS

Findings suggested that MSC-NP treatment was generally well tolerated, with no serious treatment-related side effects reported during the study. Mild headaches or fever more commonly followed MSC-NP than placebo injections. Seven participants left the study due to unrelated medical issues or personal choice.

The trial’s main goal was to determine if MSC-NP treatment could improve functional ability in patients, as assessed by either a reduction in EDSS scores; a 20% or greater improvement in walking ability, measured with the timed 25-foot walk test (T25FW); or a 20% or better improvement in arm and hand dexterity, measured with the 9-hole peg test.

Results showed it failed to meet this goal. In the first year, about one-third (33%) of patients treated with MSC-NP experienced an improvement in any of these measures, as did a slightly higher proportion (37%) of those on a placebo.

“Our primary endpoint, disappointingly, was not met,” Sadiq said, noting that there was “a very big placebo effect,” which highlights the importance of placebo-controlled studies.

Of the 47 patients who completed the two-year study — with all receiving one year of MSC-NP treatment and one year of a placebo — 43% experienced an improvement in EDSS. Disability scores were stable in 34% of these patients, and worsened in the remaining 23%.

Analyses of T25FW scores showed no significance between MSC-NP and a placebo for patients who started the study with an EDSS score of 5.5 or lower, meaning they did not need an aid to walk short distances.

But among patients with an EDSS score of 6 or 6.5, who need an aid even for short distances, there was a significant difference: average T25FW scores remained largely stable for patients given MSC-NP in the first year, whereas it declined by about 60% for those given a placebo.

The six-minute walk test (6MWD), another test of walking ability, showed similar results. There was a significant difference between the MSC-NP and placebo group among patients with more substantial walking problems at the study’s start.

“We are particularly encouraged by the improvements in walking speed among patients who require assistance, which suggests that stem cells can make a potentially life-altering difference for these patients,” Sadiq said.

Among people with bladder function problems at the start of the study, 11 of 16 (69%) who were evaluated experienced improvements after treatment with MSC-NP, as compared to four of 11 (36%) patients who were given a placebo. Two patients given MSC-NP experienced any apparent worsening of bladder function.

Analyses of biomarkers in patients’ cerebrospinal fluid (the liquid around the brain and spinal cord) were generally indicative of less inflammation and more reparative processes in the brain, while markers of nerve cell damage remained low throughout the study. MRI data also suggested that MSC-NP significantly preserved brain volume in people with a higher initial brain volume.

“The biomarker changes observed in the study show biochemical evidence of the reparative nature of stem cell treatments and can provide a valuable metric for us to further study their impact,” Sadiq said.

“We look forward to building on these findings in future research and potentially studying the effects of increasing the dosage of stem cells administered to patients,” Harris said.

Note: The Multiple Sclerosis News Today team is providing coverage of the American Academy of Neurology (AAN) 2023 Annual Meeting, April 22-27. Go here to see the latest stories from the conference.