Summary of Study ST002858
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001789. The data can be accessed directly via it's Project DOI: 10.21228/M8G43R This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002858 |
| Study Title | Intracerebroventricular Transplantation of Foetal Allogeneic Neural Stem Cells in Patients with Secondary Progressive Multiple Sclerosis (hNSC-SPMS): a phase I dose-escalation clinical trial - Metabolomics Analysis of Human Serum |
| Study Summary | This is an open-label, first-in-human, dose-escalation phase I study (NCT03282760, EudraCT2015‐004855‐37) to determine the feasibility, safety, and tolerability of the transplantation of allogeneic human neural stem/progenitor cells (hNSCs) for the treatment of progressive multiple sclerosis. We report the analysis of 1 year of data from the first cohort of 15 patients from two trial sites that received increasing numbers of allogeneic hNSCs delivered via intracerebroventricular injection in combination with an immunosuppressive regimen. No treatment-related deaths nor serious adverse events (AEs) were observed over the 12-month follow-up. Participants displayed stability of clinical and laboratory parameters, as well as lesion load and activity at the brain MRIs, compared to study entry. Longitudinal metabolomics and lipidomics analyses of cerebrospinal fluid and serum from these patients identified time and dose-dependent responses, with increased levels of free fatty acids and acylcarnitines in the CSF, especially at the highest dose of injected hNSCs at the one-year follow-up time point. Finally, a significant inverse correlation was found between the highest dose of injected hNSCs and the smaller parenchymal brain volume change (PBVC; Spearman’s rho= -0.7, p= 0.03), clinical covariates that correlated with CSF levels of free fatty acids, acyl-carnitines, oxylipins, conjugated bile acids and purine breakdown and deamination products, such as hypoxanthine. The absence of AEs and the stability of functional and structural outcomes is reassuring in terms of risks and represent a main milestone to rigorously address the challenges for the safe translation of key principles of stem cell biology into effective regenerative medicines. |
| Institute | University of Colorado Anschutz Medical Campus |
| Last Name | Stephenson |
| First Name | Daniel |
| Address | Research 1 South L18-1303 12801 E. 17th Ave., Aurora, Colorado, 80045, USA |
| daniel.stephenson@cuanschutz.edu | |
| Phone | 303-724-3339 |
| Submit Date | 2023-09-11 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzXML |
| Analysis Type Detail | GC/LC-MS |
| Release Date | 2023-09-27 |
| Release Version | 1 |
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Sample Preparation:
| Sampleprep ID: | SP002976 |
| Sampleprep Summary: | Extraction of metabolites and lipids from serum and cerebrospinal fluid (CSF) was as follows: 40 µL CSF or serum was aliquoted into 2mL deep well plates followed by an addition of 360 µL cold MeOH:MeCN:H2O (5:3:2, v:v:v). Plates were then placed on a shaker at 4°C and plate shaker was set to 400 RPM for 30 minutes. Insoluble material was pelleted by centrifugation (4000 RPM, 10 min) and supernatants were isolated for analysis by UHPLC-MS. All 96-well plate pipetting was done using Integra MINI 96 (Integra Biosciences). |
