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)

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.