ACTRIMS 2024: Progressive MS patients show gains in NG-01 OLE

Repeated treatment led to improvements in mobility, cognition

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A banner illustrates the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2024 conference.

Repeated treatment with the mesenchymal stem cell therapy NG-01 led to gains in mobility and cognition, along with patient-reported quality of life, for most people with progressive multiple sclerosis (MS) in an extension study. Markers of nerve damage were also reduced, indicating significant nerve-protecting effects.

Dimitrios Karussis, MD, PhD, of Hadassah University Hospital, Jerusalem, where the trial was conducted, discussed those findings last week in the talk “Effects of repeated autologous mesenchymal stem cell (MSC-NG01) transplantation on cognition and serum biomarkers in progressive MS: Interim analysis of an open label extension trial” at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2024, held virtually and in Florida.

NG-01 treatment involves collecting mesenchymal stem cells (MSCs) from a patient’s bone marrow. MSCs are able to grow into fat and connective tissue cells, and also secrete multiple signaling molecules that coordinate other cells’ activity. NG-01 is made of a specific population of MSCs that has anti-inflammatory and nerve-protective properties.

After collection and expansion, the cells in NG-01 are injected back into the patient where they should travel to areas of damage and inflammation in the brain and spinal cord, the hope being to reduce the inflammatory nerve damage that drives MS.

NG-01 was originally developed by Hadassah Medical Organization, which transferred the rights to NeuroGenesis for further development.

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A banner illustrates the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2024 conference.

ACTRIMS 2024: Progressive MS patients show gains in NG-01 OLE

Testing NG-01 in progressive MS

NG-01 was tested in a Phase 2 clinical trial (NCT02166021) against a placebo in people with secondary progressive MS and primary progressive MS who’d failed to respond to at least one line of MS therapy. The participants had MS for more than 12 years, on average, with moderate to severe disability.

The therapy was given intrathecally, that is, directly into the spinal canal, or intravenously into the bloodstream. The treatment group received a second NG-01 injection or a sham injection six months after the first dose and those on a placebo received NG-01 through either administration method.

The patients given NG-01 were less likely to have disability progression, although the intrathecal route resulted in greater benefits in a number of outcomes over the intravenous one.

Biomarker data also suggested the intrathecal treatment significantly reduced markers of nerve damage by 63.5% after six months, compared with a significant increase of 47.5% in the placebo group. No significant differences were observed in those who received the therapy into the vein.

Following the original trial, patients were allowed to enter an open-label extension where all received one to three intrathecal NG-01 injections, given three to six months apart. Karussis’ presentation covered interim data from 23 participants in the extension study, all of whom have received at least two injections into the spinal canal and have been followed for at least a year.

Effects of NG-01 in extension study

About two-thirds of them were male with average age of 52. Most had secondary progressive disease, 10 active and 10 nonactive, and three had primary progressive MS. Fourteen patients (60.9%) received other MS therapies in addition to NG-01, with most receiving Ocrevus (ocrelizumab).

NG-01 has been well tolerated so far. Seven patients (30%) have had mild headache, likely related to the intrathecal injection, Karussis said. There’s also been a few mild cases of COVID-19, but no “significant adverse events” were noticed.

Average scores on measures of physical and cognitive function tended to improve somewhat throughout the study, a notable contrast to progressive MS’s typical trajectory where symptoms steadily worsen over time.

Scores on the Expanded Disability Status Scale (EDSS) dropped from 6.15 points to 6.08 points, indicating most patients had stable or improved (reduced) disability levels at the latest follow-up. The average time patients took to walk 25 feet was also about a second faster at the final assessment than at the study’s start, and most patients improved by at least 3 degrees on the Single Digit Modalities Test (SDMT), a cognitive assessment.

Patient-reported quality of life, including both mental and physical well-being, also improved by 12% to 35% on average.

The most important finding has come from biomarker data, which showed a “robust reduction” in NfL and GFAP, two markers of brain damage that have been identified as powerful prognostic markers for progressive MS. NfL, or neurofilament light chain, is a marker of nerve damage. Its levels started decreasing from the first injection, an effect that “was strongly boosted by the second administration of the mesenchymal stem cells, indicating an additional effect,” Karussis said. After a year, NfL levels were 33.2% lower than before treatment, on average.

GFAP, or glial fibrillary acidic protein, is a marker of damage to astrocytes, star-shaped supportive cells in the brain and spinal cord. GFAP levels were reduced in all 23 patients, an effect that increased after the second injection. “There was not even a single patient that showed no change or increase in GFAP levels, which is a very strong indication of some efficacy of this treatment,” said Karussis, who noted that available anti-inflammatory therapies for MS have not been proven to affect GFAP.

The biomarker data, combined with changes in functional outcomes, support the idea that NG-01 could have neuroprotective effects in MS, he said.

Note: The Multiple Sclerosis News Today team is providing coverage of the ACTRIMS Forum 2024 Feb. 29-March 2. Go here to see the latest stories from the conference.