Stem cell treatment for progressive MS shows potential to protect the brain
Long-term trial data show therapy may safely slow brain shrinkage
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New data show treatment with stem cells is safe and may protect the brain in people with progressive forms of MS. (Image from iStock)
- Neural stem cell therapy for progressive multiple sclerosis appears safe in the long term, according to new data.
- The treatment showed potential to slow brain shrinkage and stabilize cognitive function, though physical disability did worsen.
- Researchers say the long-term findings warrant further clinical trials in people with progressive MS.
Treatment with neural stem cells — cells that have the ability to mature into supportive cells of the brain and spinal cord — showed early signs of neuroprotection in people with progressive forms of multiple sclerosis (MS), according to long-term follow-up data from a small early clinical trial.
The data show that the use of these specialized self-renewing cells, which can develop into neurons, or nerve cells, remained safe after nearly six years among MS patients who completed the two-year Phase 1 study, called STEMS (NCT03269071). That study was designed to evaluate the feasibility, safety, and tolerability of the experimental therapy, given directly into the spinal canal.
Among participants, cognitive function remained stable, and rates of brain tissue loss slowed to levels similar to those seen in healthy adults and people with early-stage MS, the data show. Still, physical disability among the trial’s participants continued to worsen over time, the researchers noted.
“These findings provide the rationale for a [Phase 2] clinical trial evaluating the efficacy of [this stem cell therapy] in a larger [group of progressive MS patients],” the team wrote, also noting that “no serious adverse events related to cell transplantation occurred, confirming long-term safety.”
“Although exploratory in nature, the stability of cognitive function, reduced brain atrophy [shrinkage], and consistent biomarker profiles support the hypothesis of a possible neuroprotective effect that warrants further investigation in a controlled clinical trial setting,” the researchers wrote.
The findings were described in the study “Neural stem cell transplantation in progressive multiple sclerosis: STEMS study long-term outcomes,” which was published in the journal Stem Cell Research & Therapy.
Progressive MS (PMS), which includes primary progressive MS (PPMS) and secondary progressive MS (SPMS), is a form of the chronic neurodegenerative condition in which disability gradually worsens over time. There are few treatments now available that can slow this steady decline.
Data came from 12 people with PPMS, SPMS
Scientists have been exploring whether neural precursor cells, which can develop into different types of cells in the brain and nervous system, might help protect the brain when transplanted into people with progressive MS.
In a preclinical MS model, these cells did not necessarily replace damaged tissue directly. Instead, they released substances that reduce inflammation and support the brain’s own repair processes.
The Phase 1 STEMS study was designed to evaluate the two-year safety and effectiveness of four doses of a treatment using neural precursor cells derived from human fetuses. The study involved 12 people with progressive MS: seven with PPMS and five with SPMS.
The participants received the cell transplant through an injection into the cerebrospinal fluid (CSF), the liquid surrounding the brain and spinal cord, done at a single center in Italy. Trial data showed that the treatment was safe and showed promising signs of reduced inflammatory markers in the CSF and slower brain atrophy.
Now, a team of researchers reported on the long-term outcomes of 11 of the dozen study participants who were followed at the same center for a median of 5.7 years after their cell transplant.
The data showed that the participants’ physical disability, as measured using the standard Expanded Disability Status Scale (EDSS), continued to worsen over the long-term follow-up. Scores reached a median score of 8.5, indicating patients were bedridden, compared with 7.25, meaning wheelchair-restricted, at the study’s start.
The rate at which disability worsened during long-term follow-up — an increase of 0.24 points on the EDSS scale per year — was similar to the rate before treatment and did not show improvement compared with the first two years after treatment. Hand coordination, tested with a pegboard task, also showed a decline among most of the patients.
Cognitive function, as measured by the Symbol Digit Modalities Test, which assesses how quickly a person can process information, remained fairly stable compared with before treatment but declined relative to the two-year mark.
The researchers suggested the earlier improvement seen at two years might have reflected patients getting more practice with the test rather than a true benefit. Also, this improvement faded once testing became less frequent during long-term follow-up, the data showed.
On brain scans, five participants (45%) developed new or enlarged areas of inflammation during long-term follow-up, a proportion similar to what was seen at the two-year mark. No patients showed active inflammatory lesions during this longer follow-up period.
Rate of brain shrinkage slowed significantly over time
The data did show that the rate of shrinkage in the brain’s gray matter (nerve cell bodies) slowed significantly between the two-year assessment and long-term follow-up.
Over the long-term period, the atrophy rates of gray and white matter (nerve fibers) per year were similar to those previously reported for healthy older adults and for people with early-stage MS, the researchers noted.
These rates also tended to be lower than those seen for a “reference [group] of PMS patients — who had comparable age and disease duration but lower disability,” the team wrote. According to the researchers, this “may represent an encouraging preliminary signal that warrants further investigation.”
Blood tests showed that a marker of brain injury and inflammation, called GFAP, had decreased over time, while other markers of nerve damage remained stable.
No adverse events were found to be related to the cell transplant procedure itself.
Because there was no information about patients’ pretransplant brain atrophy trajectories and no control group of patients not receiving the transplant, it remains uncertain whether the transplant caused the slower brain shrinkage or stable cognition, the researchers noted. Such observations may just reflect the natural course of the disease at this stage, the team noted.
“Although hfNPC transplantation appears safe in the medium term, its efficacy remains to be consistently demonstrated,” the researchers concluded. The team noted that “preliminary data supporting a potential for reducing neurodegeneration in PMS patients” should be studied further.
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