Kinetics of serum NFL and GFAP and changes in cognitive functions, in MS patients treated with repeated administrations of autologous mesenchymal stem cells (MSC-NG01)

J Neuroimmunol. 2025 Jun 15:403:578613. doi: 10.1016/j.jneuroim.2025.578613. Epub 2025 Apr 8.

Abstract

Background: Intrathecal injection (IT) of autologous mesenchymal stem cells (MSC) showed robust beneficial effects a previous randomized study from our center, in patients with progressive multiple sclerosis (MS) (NCT02166021). We evaluated here the effect of repeated MSC-NG01 transplantations on serum biomarkers of neuroinflammation and neurodegeneration, namely, neurofilaments light chains (NFL) and glial fibrillary acidic protein (GFAP), in an open-label extension trial.

Methods: 23 patients with progressive types of MS, who participated in the NCT02166021-trial, were included. Patients were treated with 2-3 intrathecal injections of MSC-NG01 and followed up for a period of >12 months. Safety/tolerability and various efficacy measurements, including EDSS/FS, timed 25-ft (T25FW) walking, cognitive functions, and serum levels of the biomarkers NFL and GFAP, were assessed.

Results: Serum levels of NFL and GFAP showed a gradual and consistent reduction after the intrathecal treatments with MSC-NG01, in multiple measurements. The mean NFL reduction at last observation after one year was 33.2 % (p < 0.001, Wilcoxon-paired test). Serum levels of GFAP were reduced in all tested patients (p < 0.0004, Wilcoxon-paired test). A significant improvement was observed in T25-FW and in the sum of all functional systems (FS) at the final visit of 12 months. SDMT cognitive test was also improved by a mean of >3 degrees (p = 0.0008).

Conclusion: Treatment of progressive MS patients with IT injections of autologous MSC-NG01 induced a reduction in both NFL and GFAP biomarkers levels, paralleled by beneficial effects on cognition, neurological functional tests and quality of life. These data indicate significant effects of MSC-transplantation on neurodegeneration and neuroinflammation.

Keywords: Biomarkers; Mesenchymal stem cells; Multiple sclerosis.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Biomarkers / blood
  • Cognition* / physiology
  • Female
  • Glial Fibrillary Acidic Protein* / blood
  • Humans
  • Injections, Spinal
  • Male
  • Mesenchymal Stem Cell Transplantation* / methods
  • Middle Aged
  • Multiple Sclerosis* / blood
  • Multiple Sclerosis* / therapy
  • Multiple Sclerosis, Chronic Progressive* / blood
  • Multiple Sclerosis, Chronic Progressive* / psychology
  • Multiple Sclerosis, Chronic Progressive* / therapy
  • Neurofilament Proteins* / blood
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • Biomarkers
  • GFAP protein, human
  • Glial Fibrillary Acidic Protein
  • neurofilament protein L
  • Neurofilament Proteins