Nurown (MSC-NTF Cells) Phase 2 Clinical Trial in Progressive MS: Effects on Monocular and Bionocular Low Contrast Letter Acuity (LCLA) Outcomes

Background:

MSC-NTF cells (NurOwn^®) are autologous bone-marrow derived mesenchymal stem cells induced to secrete high levels of neurotrophic factors while maintaining their intrinsic immunomodulatory properties. Both neuroprotection and neuroinflammation influence outcomes in the optic nerve transection¹ and EAE models². Intravitreal MSC-NTF cell administration was shown to improve survival of retinal ganglion cells in the optic nerve transection model³ and intracerebroventricular administration of MSC-NTF cells improves motor outcomes and survival in the EAE model⁴.

Objectives:

In this analysis, we evaluated the impact of MSC-NTF cell therapy on monocular and binocular LCLA outcomes in patients in a phase 2 clinical trial of progressive MS (NCT 03799718).

Methods:

Eligible participants had baseline Expanded Disability Status Scale (EDSS) scores between 3-6.5, no 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. LCLA was performed along with other standard MS functional and disability outcomes (and CSF biomarkers) at baseline and week 28. Monocular and binocular LCLA outcomes were compared to matched CLIMB registry patients (n=48) and matched placebo participants from NN-102 SPRINT-MS study (N=123)⁵.

Results:

Following MSC-NTF treatment at week 28, LCLA 2.5% threshold (n=15) improved (number of letters) from baseline by 5.8 (OD), 3.9 (OS), and 3.3 (Binocular), compared to -0.93, -0.41, and -1.07 reductions for matched CLIMB patients (N=48), and -0.5, -1.2, and -0.6 reductions for NN-102 SPRINT-MS placebo participants (N=123). Corresponding responder rates (≥8 letter improvement) over 28 weeks at 2.5% threshold were 40% (OD), 27% (OS), and 27% (binocular) inphase 2 participants treated with MSC-NTF cells, compared to 0% (OD), 6% (OS), and 6% (binocular) in CLIMB, and 14% (OD), 13% (OS) and 13% (binocular) in NN-102 SPRINT-MS placebo, respectively. At 1.25% threshold, LCLA improvements of 7.3 (OD), 7.1 (OS) and 5.0 (binocular) were observed, along with responder rates of 40%, 27% and 47% respectively. 1.25% threshold LCLA data were not available from CLIMB or NN-102 SPRINT-MS for comparison.

Conclusions:

MSC-NTF cell treatment resulted in improvements in both monocular and binocular LCLA assessments at 2.5% and 1.25% thresholds. These effects may be related to a combination of neuroinflammatory and neuroprotective mechanisms. Further studies are needed to confirm these promising observations and to further explore the putative mechanism of action of MSC-NTF cells in progressive MS and in disorders affecting the visual pathways.

References:

1. Chen, Development 2021
2. Horstmann, J Neuroinflamm 2013
3. Levkovitch-Verbin, Vis Sci 2010
4. Barhum, J Mol Neurosci 2010
5. Fox, NEJM 2018