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Clinical Trial
. 2024 May 23;15(1):151.
doi: 10.1186/s13287-024-03765-6.

Efficacy of intrathecal mesenchymal stem cell-neural progenitor therapy in progressive MS: results from a phase II, randomized, placebo-controlled clinical trial

Violaine K Harris  1 , James Stark  1 , Armistead Williams  1 , Morgan Roche  1 , Michaela Malin  1 , Anjali Kumar  1 , Alyssa L Carlson  1 , Cara Kizilbash  1 , Jaina Wollowitz  1 , Caroline Andy  2 , Linda M Gerber  2 , Saud A Sadiq  3
Affiliations
Clinical Trial

Efficacy of intrathecal mesenchymal stem cell-neural progenitor therapy in progressive MS: results from a phase II, randomized, placebo-controlled clinical trial

Violaine K Harris et al. Stem Cell Res Ther. .

Abstract

Background: Mesenchymal stem cell-neural progenitors (MSC-NPs) are a bone marrow mesenchymal stem cell (MSC)-derived ex vivo manipulated cell product with therapeutic potential in multiple sclerosis (MS). The objective of this study was to determine efficacy of intrathecal (IT) MSC-NP treatment in patients with progressive MS.

Methods: The study is a phase II randomized, double-blind, placebo-controlled clinical trial with a compassionate crossover design conducted at a single site. Subjects were stratified according to baseline Expanded Disability Status Scale (EDSS) (3.0-6.5) and disease subtype (secondary or primary progressive MS) and randomized into either treatment or placebo group to receive six IT injections of autologous MSC-NPs or saline every two months. The primary outcome was EDSS Plus, defined by improvement in EDSS, timed 25-foot walk (T25FW) or nine-hole peg test. Secondary outcomes included the individual components of EDSS Plus, the six-minute walk test (6MWT), urodynamics testing, and brain atrophy measurement.

Results: Subjects were randomized into MSC-NP (n = 27) or saline (n = 27) groups. There was no difference in EDSS Plus improvement between the MSC-NP (33%) and saline (37%) groups. Exploratory subgroup analysis demonstrated that in subjects who require assistance for ambulation (EDSS 6.0-6.5) there was a significantly higher percentage of improvement in T25FW and 6MWT in the MSC-NP group (3.7% ± 23.1% and - 9.2% ± 18.2%) compared to the saline group (-54.4% ± 70.5% and - 32.1% ± 30.0%), (p = 0.030 and p = 0.036, respectively). IT-MSC-NP treatment was also associated with improved bladder function and reduced rate of grey matter atrophy on brain MRI. Biomarker analysis demonstrated increased MMP9 and decreased CCL2 levels in the cerebrospinal fluid following treatment.

Conclusion: Results from exploratory outcomes suggest that IT-MSC-NP treatment may be associated with a therapeutic response in a subgroup of MS patients.

Trial registration: ClinicalTrials.gov NCT03355365, registered November 14, 2017, https://clinicaltrials.gov/study/NCT03355365?term=NCT03355365&rank=1 .

Keywords: Cell therapy; Clinical trial; Intrathecal; MSC-NP; Mesenchymal stem cell; Multiple sclerosis; Progressive multiple sclerosis.

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Conflict of interest statement

VH and SS are listed as inventors on a US patent issued to the Tisch MS Research Center of New York and is considered a non-financial competing interest. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Trial design and enrollment IT, intrathecal; MSC-NP, mesenchymal stem cell-derived neural progenitor
Fig. 2
Fig. 2
Walking outcomes after MSC-NP treatment compared to saline. Percentage change in (a) T25FW time and (b) 6MWT distance after one year of MSC-NP or saline treatments compared to baseline. Subjects were grouped by low EDSS (EDSS 3.0-5.5) (top graphs) or high EDSS (EDSS 6.0-6.5) (bottom graphs). Values represent mean and standard deviation. ns, not significant
Fig. 3
Fig. 3
MSC-NP treatment was associated with improved bladder function and reduced PVR. (a) 76% (13/17) subjects treated with MSC-NPs demonstrated improved bladder function after one year, compared to 27% (3/11) subjects treated with saline. (b) PVR volume was measured before and after one year of either saline or MSC-NP injections. MSC-NP treatment was associated with a significant reduction in PVR volume (ml) compared to saline injections
Fig. 4
Fig. 4
MSC-NP treatment was associated with preservation of grey matter atrophy. Subjects were grouped into either (a) the upper percentile (50–100%) or (b) the lower percentile (0–50%) based on their normative grey matter volume at baseline. In the upper percentile group, there was a significant difference in the percentage change of grey matter volume after one year of MSC-NP treatment compared to saline treatment when calculated as absolute grey matter volume or as a percentage of intra-cranial volume (%ICV). Percentage change was not different between MSC-NP and saline in the lower percentile group. ns, not significant
Fig. 5
Fig. 5
Increased MMP9 and decreased CCL2 in CSF following MSC-NP treatment. (a) CSF MMP9 levels pre- and post-MSC-NP treatment in all 50 phase II subjects. (b) Longitudinal changes in CSF MMP9 levels in the 26 subjects who received saline in year one and MSC-NPs in year two. One outlier subject exhibited much higher CSF MMP9 levels and is graphed separately in (c). MMP9 levels were unchanged over year one (saline) and significantly increased after year two following MSC-NP treatment. Outlier was included in the statistical analysis. (d) CSF CCL2 levels pre- and post-MSC-NP treatment in all trial subjects divided into responder (n = 23) (left panel) and non-responder (n = 26) (right panel) subgroups. Biomarker values from one subject was removed from analysis due to missing outcome data. Decreased CCL2 was statistically significant in responders (left panel) but not in non-responders (right panel). (e) Longitudinal changes in CSF CCL2 levels in the 26 subjects who received placebo in year 1 and MSC-NPs in year 2. CCL2 levels were unchanged over year one (placebo) and significantly decreased in year two following MSC-NP treatment
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References

    1. Dobson R, Giovannoni G. Multiple sclerosis - a review. Eur J Neurol. 2019;26(1):27–40. doi: 10.1111/ene.13819. - DOI - PubMed
    1. Reich DS, Lucchinetti CF, Calabresi PA. Multiple sclerosis. N Engl J Med. 2018;378(2):169–80. doi: 10.1056/NEJMra1401483. - DOI - PMC - PubMed
    1. Bo L, Vedeler CA, Nyland HI, Trapp BD, Mork SJ. Subpial demyelination in the cerebral cortex of multiple sclerosis patients. J Neuropathol Exp Neurol. 2003;62(7):723–32. doi: 10.1093/jnen/62.7.723. - DOI - PubMed
    1. Correale J, Gaitan MI, Ysrraelit MC, Fiol MP. Progressive multiple sclerosis: from pathogenic mechanisms to treatment. Brain. 2017;140(3):527–46. - PubMed
    1. Kutzelnigg A, Lucchinetti CF, Stadelmann C, Bruck W, Rauschka H, Bergmann M, et al. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain. 2005;128(Pt 11):2705–12. doi: 10.1093/brain/awh641. - DOI - PubMed

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