Repeated Intrathecal Injection of NeuroGenesis’ Mesenchymal Stem Cell Therapy Reveals Potential Benefit in Progressive MS


A recent analysis of a phase 2 trial showed that repeated intrathecal injections of MSC therapy led to significant reductions in serum biomarkers and improvements in neurological function for progressive MS.

Dimitrios Karussis, MD, PhD, head of the MS Center at Hadassah Medical Center, in Jerusalem, Israe

Dimitrios Karussis, MD, PhD

Credit: Hadassah BrainLabs

In a new interim analysis of a phase 2 double-blind randomized trial (NCT02166021), findings showed patients with progressive MS maintained a continuous reduction of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) with repeated intrathecal injection (IT) of NeuroGenesis’ mesenchymal stem cell (MSC) therapy, NG-01. These results suggest repeated IT NG-01 has potential significant beneficial effects on cognition and serum biomarkers of neuroinflammation and neurodegeneration in progressive MS.1,2

In this open label extension trial of 23 patients, serum levels of NfL and GFAP showed a gradual and consistent significant reduction by a mean of approximately 20% in multiple measurements after receiving IT MSC. Investigators reported a mean reduction in NfL of 33.2% in 20 patients (P <.0008; Wilcoxon matched-pair test), and a mean reduction in GFAP of 22% in 23 patients both from baseline to the last observation after 2nd dosing (P <.00008; Wilcoxon matched pair test).

“We found that repeated intrathecal injections of autologous MSC-NG01 in patients with progressive MS induced a robust and consistent reduction of the serum levels of the 2 most reliable biomarkers of disease activity and neurodegeneration, NFL and GFAP, with a linear and cumulative effect, in multiple measurements,” senior author Dimitrios Karussis, MD, PhD, head of the MS Center at Hadassah Medical Center, in Jerusalem, Israel, told NeurologyLive®. “It was surprising that whilst several of the MS immunotherapies, were shown to reduce serum NFLs, their effects on GFAP levels are minimal (or absent).”

Top Clinical Takeaways

  • Repeated intrathecal injections of MSC therapy, NG-01, demonstrated consistent reductions in serum biomarkers associated with MS progression.
  • Improvements in neurological function, including cognitive function and walking ability, were observed alongside reductions in serum biomarkers.
  • The trial suggests the potential neuroprotective effects of NG-01 therapy in progressive MS, highlighting a promising avenue for treatment.

Presented at the 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, February 29 to March 2, in West Palm Beach, Florida, the interim analysis, originally intended to have 40 patients from the prior phase 2 study, included patients (men, n = 14; women, n = 9; mean Expanded Disability Status Scale [EDSS], 5.9 [+0.8]) with a follow up period of 12-18 months. Participants with progressive MS were treated with at least 2 intrathecal injections of MSC, 3-6 months apart. Investigators assessed the safety, tolerability, and efficacy measurements of NG-01, including EDSS Functional systems, 25-feet walk (25 FWT), cognitive functions as well as changes in the serum levels of the biomarkers NfL and GFAP.

READ MORE: Machine Learning Model Enhances Real-World Studies for Predicting Disability Progression in Multiple Sclerosis

“Our findings, taken together with the neurological benefits in other parameters of MS-progression (cognitive functions, walking ability, functional systems), provide an additional objective indication of neuroprotective or neurotrophic effects of treatment with MSC-NG01 in progressive MS, in which most of the currently available treatments do not have a significant effect,” Karussis, who also serves as the cofounder and chief scientific officer of NeuroGenesis, said.

In 16 of the participants with multiple measurements of 25 FWT, investigators observed a significant improvement by a median of 17% following the first injection and 4.5% after 1 year (mean reduction by 1 second at 12 months, P = .049). Notably, researchers reported a reduction in the sum of all functional systems at the final end-point of 12-18 months, from 10.86 (±3.14) to 9.98 ([±3.04]; P = .003). Additionally, patient’s scores on Symbol Digit Modalities Test (SDMT) cognitive test improved by a mean of approximately 2 degrees (from 42.9 [±11.9], to 45.0 [±12.3], P = .01) and patient reported outcomes all improved significantly by 12%-35%.

Authors noted participants reported no serious adverse events (AEs) with NG-01 and the only minor AEs reported during the study included headache in 9 patients and backache in 2 patients. These reported AEs were considered by the investigators as procedure-related and were resolved in 48 hours after the lumbar puncture.2

“Next steps include an extension of the current study with more patients (this was on 23 patients) and the preparation of a multi-center trial with MSC-NG01 in progressive MS, in which 6 major centers in USA have agreed to participate (and we have already FDA approval for this),” Karussis added.

In the previous phase 2 study, data showed that IT NG-01 significantly reduced NfL in a cohort of patients with progressive MS.3,4 In the trial, 44 participants were included randomized to either IT (n = 15) or intravenously (IV) injection (n = 15) of NG-01 or placebo (n = 14). Cerebrospinal fluid (CSF) samples collected at baseline showed that NfL concentrations were exceptionally high in almost all patients (more than 10,000 pg/mL in 8 of 15 in IT group, 7 of 15 in IV group, and 7 of 14 in placebo), indicating an aggressive disease behavior. Following 6 months of treatment with IT NG-01, patients demonstrated a median reduction of 63.5% in CSF NfL levels, whereas those in the placebo group showed an increase of 47.5%, indicating deterioration.

A smaller, more insignificant reduction was seen among patients who received NG-01 IV. Nine of 15 patients in the IT group showed a reduction in NfL levels of more than 50% (median decrease, –4449 pg/mL) compared with only 1 of 14 patients in the placebo group (X2 test, P = .001). Furthermore, 8 of 9 patients who demonstrated this reduction had either stable or improved EDSS scores, and 7 of 9 patients improved in the sum score of all the functional systems of the EDSS, at 6 months. At 12-month follow-up, 8 of 9 individuals continued to show an improved score.

Click here for more coverage of ACTRIMS 2024.

1. Petrou P, Kassis I, Yaghmour N, Epstein T, Ginzberg A, Karussis D. Effects of Repeated Autologous Mesenchymal Stem Cell Transplantation on Cognition and Serum Biomarkers in Progressive MS: Interim Analysis of an Open Label Extension Trial. Presented at ACTRIMS Forum 2024; February 29 to March 2; West Palm Beach, Florida. LB1 Session.
2. NeuroGenesis Reports Positive Results from Phase 2 Extension Study in Progressive Multiple Sclerosis Treated with NG-01 Cell Therapy. News Release. NeuroGenesis. Published March 12, 2024. Accessed March 12, 2024.
3. NeuroGenesis and Hadassah Medical Center report positive NF-L biomarker results from a phase 2 study in progressive multiple sclerosis treated with NG-01 cells therapy. News release. NeuroGenesis. March 1, 2022. Accessed March 13, 2024.
4. Petrou P, Kassis I, Ginzberg A, Hallimi M, Karussis D. Effects of mesenchymal stem cell transplantation on cerebrospinal fluid biomarkers in progressive multiple sclerosis. Stem Cells Transl Med. Published online February 15, 2022. doi:10.1093/stcltm.szab017
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