Effect of Intrathecal Injection of Mesenchymal Stem Cell-Neural Progenitors on Cerebrospinal Fluid Biomarkers in Progressive Multiple Sclerosis

Mesenchymal stem cell-neural progenitors (MSC-NP) are a bone marrow-derived population of cells with trophic and immunomodulatory properties with therapeutic potential in multiple sclerosis (MS). Early phase clinical trials have demonstrated safety and efficacy of intrathecal administration of autologous MSC-NPs in people with progressive MS. To better understand the mechanisms and clinical effects of MSC-NP treatment, we analyzed cerebrospinal fluid (CSF) biomarkers in two separate cohorts of trial subjects with nonactive progressive MS from both a phase 2 trial (n = 50) and an expanded access trial (n = 43) who received repeated administrations of autologous MSC-NPs. Candidate biomarkers identified through proteomic screening were validated in both cohorts, revealing a panel of four biomarkers (CCL2, C-C motif chemokine ligand-2; MMP9, matrix metalloproteinase-9; SCF, stem cell factor/c-kit ligand; and CHIT1, chitotriosidase-1) that were significantly changed in CSF but not serum following treatment. Other MS biomarkers neurofilament light (NfL) and glial acidic fibrillary protein (GFAP) were unchanged following treatment but correlated with age, and both age and EDSS, respectively. The specific biomarker changes together with the clinical benefits observed following MSC-NP injections suggest distinct biological effects following MSC-NP treatment. These biomarkers may help explain the basis of MSC-NP therapy therapeutic effects as well as guide dose optimization.