NIB02
Nurown (MSC-NTF) Phase 2 Clinical Trial in Progressive MS: Effects on CSF Inflammatory Biomarkers
MSC-NTF cells (NurOwn®) are autologous bone-marrow derived mesenchymal stem cells (MSC) induced to secrete high levels of neurotrophic factors (NTFs) while maintaining their intrinsic immunomodulatory properties. MSC-NTF cells were evaluated in a phase 2 clinical trial in progressive MS (NCT 03799718). Safety, consistent improvements in MS functional outcomes and biomarker results were collected. CSF inflammatory biomarkers such as Osteopontin (OPN), soluble CD27 (sCD27) and stromal derived factor (SDF-1a), shown in recent studies to be relevant to progressive MS natural history and treatment outcomes.1,2,3,4
Objectives:
We performed analyses on the effects of MSC-NTF cell treatment on these and other key inflammatory biomarkers in the phase 2 clinical trial.
Methods:
Eligible participants had baseline Expanded Disability Status Scale (EDSS) scores between 3-6.5, no clinical relapses within 6 months of study enrollment, and were able to walk 25 feet in 60 seconds or less. Participants received 100-125M intrathecal MSC-NTF cells by lumbar puncture at weeks 0, 8, and 16 and then were followed to week 28. CSF was collected at weeks 0, 8 and 16 (just prior to third treatment).
Inflammatory biomarkers (OPN, sCD27, MCP-1 SDF-1, and CHIT-1) were detected with a highly sensitive, customized ProcartaPlex multiplex immunoassay (Thermo Fisher Scientific, Waltham, MA; and an ELISA kit from MBL for CHIT-1). The assays were thoroughly validated by matrix evaluation including spike recovery, parallelism, and sample stability. Biomarker data were log transformed for analysis and percent changes were graphed in the original units. We present geometric means and the first (Q1) and third (Q3) quartiles.
Results:
At week 16 following 2 MSC-NTF cell treatments we observed % reductions [geometric mean, (Q1,Q3)] from baseline of 30 (-42,13), 9 (-13,3), 8 (-27,10) and 6 (-14,1) in CSF OPN, sCD27, MCP-1 and SDF-1a, respectively. CHIT-1 was increased by 18 (4,33)% from baseline at week 16.
Conclusions:
In this phase 2 clinical trial, MSC-NTF cell treatment resulted in consistent reductions in CSF inflammatory biomarkers (OPN, sCD27, and SDF-1a) that may be relevant to disease progression and treatment response in progressive MS. These observations may guide future efforts to optimize this innovative autologous mesenchymal cellular therapy in progressive MS.
References:
- Christensen 2014
- Christensen 2019
- Milstein 2019
- Marastoni 2021