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Abstract Details

Cerebrospinal Fluid Biomarkers Associated with Intrathecal Cell Therapy in Patients with Progressive Multiple Sclerosis
Multiple Sclerosis
P1 - Poster Session 1 (8:00 AM-9:00 AM)

MSC-NPs are a bone marrow-derived population of cells with trophic and immunomodulatory properties with therapeutic potential in MS. A phase II randomized, double-blind, placebo-controlled clinical trial was performed to investigate whether multiple intrathecal (IT) injections of autologous MSC-NPs was associated with clinical efficacy. Study subjects received either 6 IT injections of autologous MSC-NPs or 6 placebo injections spaced 2 months apart. In the crossover study design, subjects treated with placebo in the first year were treated with MSC-NPs in the second year, and vice versa. Safety and clinical efficacy will be reported elsewhere. 

To identify cerebrospinal fluid (CSF) biomarkers of clinical response to intrathecal (IT) mesenchymal stem cell-neural progenitor (MSC-NP) treatment in patients with progressive multiple sclerosis (MS).

For biomarker discovery, CSF was collected from 36 study subjects at the time of their first and sixth IT-MSC-NP treatment reflecting pre-treatment and post-treatment timepoints, respectively. CSF supernatants were analyzed using SOMAScan multiplex proteomic assay. Differentially expressed proteins were identified using a multivariate linear mixed effect model. Biomarkers were validated using ELISA/Luminex assays. Treatment responders were defined by improvement in any of the following outcomes: EDSS, timed 25-foot walk, 9-hole peg test, 6-minute walk test, or muscle strength.

Proteomic analysis of CSF identified matrix metalloproteinase-9 (MMP-9), complement C3a and the chemokine CCL2 as potential biomarkers of IT-MSC-NP treatment. MMP-9 was significantly increased post-treatment and was observed independent of clinical response. Relative concentration of C3a, C3 and C3b were decreased post-treatment and subgroup analysis demonstrated significance only in the responder group. CCL2 was significantly decreased post-treatment with higher significance associated with clinical response. Decreased CCL2 was validated in an independent cohort of patients treated with IT-MSC-NPs. 

These results identify multiple CSF biomarkers of IT-MSC-NP treatment that may correlate with therapeutic response to this novel cell therapy in MS. 
Cara Kizilbash (Tisch MS Research Center of New York)
Miss Kizilbash has nothing to disclose.
Alyssa Carlson (Tisch MS Research Center of New York) Ms. Carlson has nothing to disclose.
Violaine K. Harris, PhD (Tisch Multiple Sclerosis Research Center of NY) No disclosure on file
Saud A. Sadiq, MD, MB, FAAN (Tisch Multiple Sclerosis Research Center of New York) Dr. Sadiq has nothing to disclose.