Abstract Details

Title Serum Neurofilament Light Chain in a Phase 1/2 Trial of Autologous Mesenchymal Stem Cell Transplantation in Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-039

Objective

To assess sNfL-c in MS patients versus controls, correlation of sNfL-c and measures of MS disease activity/severity, and treatment effect of MSC transplantation on sNfL-c in a phase 1/2 trial.

Background

Serum neurofilament light chain (sNfL-c) is a putative biomarker of axonal injury in multiple sclerosis (MS). Mesenchymal stem cells (MSCs) have anti-inflammatory and repair-promoting activities, making them of interest for potential MS treatment.

Design/Methods 24 patients with MS received one IV infusion of autologous culture-expanded MSCs. Clinical assessments (Expanded Disability Status Scale, MS Functional Composite-4), standard/advanced MRI, optical coherence tomography, and visual evoked potentials were performed at Months (M) -1, 0 (transplant), 1, 2, 3, and 6. Serum was collected from 22 of 24 trial participants at M0, 1, 3, 6 and once from age- and sex-matched healthy controls (n=10). sNfL-c was measured by single-molecule array. MS versus control sNfL-c was compared by Wilcoxon rank sum testing. Cross-sectional associations of sNfL-c with disease measures were analyzed by Spearman correlations. Pre-post transplant sNfL-c (M1/3/6 versus M0) was compared by Wilcoxon signed rank testing for paired samples.

Results sNfL-c was higher (p=0.0007) in MS patients (median 14.72 pg/ml) versus controls (6.92 pg/ml), and was similar in RRMS and SPMS. There were significant (p<0.01) correlations between increased sNfL-c and gadolinium-enhancing lesion number (rho=0.55) and volume (rho=0.65), and new/enlarged T2 lesions (rho=0.65). No significant correlations were observed between sNfL-c and advanced MRI, clinical, or vision measures. sNfL-c decreased at M1 (median -0.91 pg/ml), M3 (-0.11 pg/ml), and M6 (-0.75 pg/ml), but differences were not statistically significant.

Conclusions sNfL-c was higher in MS patients compared to controls, correlated with measures of MRI lesion activity, and trended downward following MSC transplantation. These results support the utility of sNfL-c as a clinical trial outcome and suggest possible benefit of autologous MSC transplantation in MS.

Authors/Disclosures
Laura E. Baldassari, MD, MHS (US Food and Drug Administration) PRESENTER	No disclosure on file
Sarah M. Planchon Pope, PhD, CCRP (Cleveland Clinic)	Dr. Planchon Pope has nothing to disclose.
	No disclosure on file
Robert A. Bermel, MD, FAAN (Cleveland Clinic)	Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi/Genzyme. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech/Roche. Dr. Bermel has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Bermel has received research support from Biogen. The institution of Dr. Bermel has received research support from Roche. The institution of Dr. Bermel has received research support from Novartis. Dr. Bermel has received intellectual property interests from a discovery or technology relating to health care.
Kunio Nakamura, PhD (Cleveland Clinic)	Dr. Nakamura has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for INmune Bio. The institution of Dr. Nakamura has received research support from Biogen. The institution of Dr. Nakamura has received research support from PCORI. The institution of Dr. Nakamura has received research support from NIH. The institution of Dr. Nakamura has received research support from Genzyme. The institution of Dr. Nakamura has received research support from NIH. The institution of Dr. Nakamura has received research support from Genzyme. The institution of Dr. Nakamura has received research support from Novartis. The institution of Dr. Nakamura has received research support from DOD. Dr. Nakamura has received intellectual property interests from a discovery or technology relating to health care.
Elizabeth Fisher	Elizabeth Fisher has received personal compensation for serving as an employee of Biogen. Elizabeth Fisher has stock in Biogen. Elizabeth Fisher has received intellectual property interests from a discovery or technology relating to health care.
Jenny J. Feng, MD (Ochsner Clinic)	Dr. Feng has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Feng has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Dr. Feng has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Feng has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon.
	No disclosure on file
Daniel Ontaneda, MD, PhD, FAAN (Cleveland Clinic)	Dr. Ontaneda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Ontaneda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech/Roche. Dr. Ontaneda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen Idec. Dr. Ontaneda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Ontaneda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. The institution of Dr. Ontaneda has received research support from NIH. The institution of Dr. Ontaneda has received research support from PCORI. The institution of Dr. Ontaneda has received research support from NMSS. The institution of Dr. Ontaneda has received research support from Genetech.
Jeffrey A. Cohen, MD (Cleveland Clinic)	Dr. Cohen has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Convelo. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astoria. Dr. Cohen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viatris. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PSI. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celltrion.

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