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 mesenchymal stem cell-derived population of cells with trophic and immunomodulatory properties with therapeutic potential in multiple sclerosis (MS). Early phase clinical trials have investigated the safety and efficacy of intrathecal administration of autologous MSC-NPs in people with progressive MS. To better understand the biological response to MSC-NP treatment, we analyzed cerebrospinal fluid (CSF) biomarkers in 2 separate cohorts of trial subjects with secondary progressive or primary 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 4 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 and glial fibrillary acidic protein were unchanged following treatment but correlated with age, and both age and Expanded Disability Status Scale (EDSS), respectively. The specific biomarker changes observed following MSC-NP injections suggest distinct biological effects following MSC-NP treatment. These biomarkers help define the pharmacodynamic response to MSC-NP treatment as well as guide the design of future clinical studies.