Stem Cell Therapy Shows 2-year Benefit for Progressive MS Patients in Phase 1 Trial

Lesser or stable disability over two years was evident in most progressive multiple sclerosis (MS) patients given a stem cell treatment in a small Phase 1 clinical trial, supporting a larger study now underway, researchers report.

These results suggest that a treatment using mesenchymal stem cell-derived neural progenitors (MSC-NPs) can safely and effectively ease inflammation in progressive MS.

But for a subset of patients, particularly those with more advanced disease and greater disability, this treatment did not sufficiently counter a continued inflammatory response in the brain.

The study, “Mesenchymal stem cell-derived neural progenitors in progressive MS: Two-year follow-up of a phase I study,” was published in the journal Neurology: Neuroimmunology and Neuroinflammation.

MSC-NPs are seen as a possible way of treating people with progressive MS, who have few effective disease-modifying treatments available. They are essentially stem cells collected from a patient’s bone marrow that are expanded and matured to produce factors involved in modulating the immune response and in nervous tissue growth and survival.

An open-label Phase 1 trial (NCT01933802) investigated this stem cell treatment  in 20 adults with stable primary (four PPMS patients) or secondary progressive MS (16 SPMS patients) and significant disability.  

All received a total of three injections of MSC-NPs, given directly into the spinal canal three months apart. They were then evaluated at three and six months, and again at two years, after the final treatment to determine its long-term safety and tolerability, and for signs of potential effectiveness. 

An initial analysis at six months post-treatment found lesser disability in most trial participants (15 of the 20) and better muscle strength in 14 of them. Greater exercise capacity was also seen in four of the 10 patients able to walk at the study’s start, and two nonambulatory patients gained an ability to walk using assistive devices.

Researchers now reported clinical findings at two years after treatment. All 20 completed two-year follow-up assessments, but two who “were severely disabled” could not do a final in-person visit. They were examined via telemedicine and did not provide biomarker samples.

Disability was evaluated using the Expanded Disability Status Scale (EDSS), in which a higher score indicates more severe disability. The two who moved to telemedicine had EDSS scores of 8.0.

At six months, eight participants had an EDSS reduction of at least 0.5 points, including four with disability reductions of two or more points. At the two-year follow-up, seven of these eight people continued to show improvements in their EDSS scores, including two who showed a sustained 2.0 or more point reduction.

The eighth patient, whose disability had initially improved by one point, showed a worsening in disability at two years.

Of the 10 patients without initial improvements in EDSS scores, six had no evidence of disease progression throughout the study and follow-up. Two others worsened at each follow-up, and two showed worsening disease between the six-month and two-year examinations.

Of the 10 nonambulatory patients at the trial’s start, four showed improvements in walking speed greater than 20% at three months post-treatment. At two years, three had maintained these walking speed gains, while one fell just below the 20% improvement mark.

One of the two people unable to walk at the beginning of the study completed the walking test at both the three-month and two-year exams. One other patient, with an initial normal walking speed, maintained that speed throughout the trial and follow-up periods.

These results indicate that multiple MSC-NP treatments led to disability reduction for most progressive patients with long-standing disease. But those who sustained these gains at two years after treatment had “lower EDSS and ambulatory status at baseline” or the study’s start, the researchers wrote.

A subset of patients with initial improvement failed to maintain shown benefits, while others showed no disease progression throughout the follow-up.

Cerebrospinal fluid (CSF) levels of CCL2, a pro-inflammatory factor, were lower following treatment, while levels of the anti-inflammatory TGF beta 2 rose post-treatment, consistent with previous studies of similar treatments.

Interestingly, no difference here was observed between patients whose disability improved in response to the treatment (responders) and those who failed to improve (non-responders).

However, some inflammatory factors were seen to rise after treatment in non-responders, but not among those who responded to treatment. This suggests that a continued inflammatory response may hinder clinical response to MSC-NP use.

Neurofilament light chain (NfL) levels in the CSF, a marker of nerve cell degeneration and damage, can be elevated in MS patients. Among “a small number” of trial patients with high NfL levels prior to treatment, these levels rose further in nonresponders after treatment while they declined among responders.

“We observed that most subjects who received repeated [MSC-NP] injections exhibited either a reversal in disability or lack of disease progression that was sustained for 2 years after treatment,” the researchers wrote.

“The impact of any efficacy conclusion, however, are severely limited by the very small number of patients in the study and the lack of blinding and placebo controls,” they added.

An ongoing and placebo-controlled Phase 2 clinical trial (NCT03355365), which opened last year, is now investigating the safety and efficacy of repeat MSC-NP injections in progressive MS patients. The study is expected to have enrolled 50 adults with progressive MS (40 SPMS and 10 PPMS), being given a total of six injections of either MSC-NPs or a placebo every other month for a first year.

In its second year, those in the MSC-NP group cross to the placebo group and those previously on a placebo move to treatment — again for six total injections given every two months. This single-site trial at the Tisch MS Research Center of New York will run for three years, and is expected to finish in late 2023.