Summary of Study ST002416

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 PR001555. The data can be accessed directly via it's Project DOI: 10.21228/M8PT4W This work is supported by NIH grant, U2C- DK119886.

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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.

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Study IDST002416
Study TitleProteomics and metabolomics of multiple sclerosis (Part 2)
Study SummaryMultiple sclerosis (MS) is a chronic autoimmune disease that affects the myelination of the neurons present in the central nervous system (CNS). The exact etiology of MS development is unclear, but various environmental and genetic factors might play a role in initiating the disease. Current treatments for MS enhance the quality of life and reduce the symptoms. One of these treatments is dimethyl fumarate (DMF), commercially known as Tecfidera. Experimental autoimmune encephalomyelitis (EAE) is a mouse model that is used to study the pathophysiology of MS disease as well as the effects of possible therapeutic agents. In this study, we investigated the effects of SIMR1707 which is a novel compound designed at Sharjah Institute for Medical Research (SIMR). . Single and multiple doses of SIMR1707 demonstrated high safety in mice studies. Treatment of EAE mice with SIMR1707 was able to reduce the EAE clinical scores and maintain their body weight similar to the MS FDA-approved (DMF, Tecfidera), when they were used preventively, prophylactically, or therapeutically. The histological and immunohistochemistry evaluations showed reduced clinical features such as signs of inflammation, demyelination, and infiltration of CD3-positive T cells into the brains of the EAE mice, as compared to vehicle-treated, or untreated EAE mice. Moreover, multi-OMICS experiments including Transcriptomics, Proteomics and Metabolomics were performed to gain insights into the relevant mechanism of action of the SIMR1707 in EAE and thus its therapeutic efficacy to treat MS. Same tissue samples extracted from the cerebellum part of the brain of normal, EAE vehicle-treated, and therapeutic SIMR1707 treated mice, were subjected for the whole RNA-sequencing for transcriptomics, Nano MS for proteomics analysis and LC-MS metabolomics analysis. The multi-OMICs integrative analysis showed that the treatment with SIMR1707 downregulated key biomarkers functionally associated with top pathways including calcium signaling, PI3K/AKT, and mTOR signaling pathways, which may play important roles in EAE and MS pathophysiology. Additionally, the metabolomics-based enriched-for-action pathway analysis showed that the top significantly activated metabolites (FC > 2, p < 0.05) are cholic acid, propionic acid, sphinganine, and nutriacholic acid. Consisting with the functional enrichment pathway analysis, two potent markers, Snta1 and Fscn1, involved in the actin-binding and cytoskeleton are commonly shared between transcriptomics and proteomics and showed mRNA-protein expression correlation in SIMR1707 treated compared to vehicle EAE mice. Importantly, these two markers are involved in the MT2/AKT/GSK3 pathway and may potentially play role in MS and EAE disease
Institute
Sharjah Institute for Medical Research
Last NameFacility
First NameCore
AddressM32, SIMR, College of Pharmacy, Health Sciences, University of Sharjah
Emailtims-tof@sharjah.ac.ae
Phone065057656
Submit Date2022-12-19
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2023-06-01
Release Version1
Core Facility Core Facility
https://dx.doi.org/10.21228/M8PT4W
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Group
SA242049N03-02_9_1_1408Normal
SA242050N03-03_9_1_1409Normal
SA242051N02-03_8_1_1406Normal
SA242052N01-01_7_1_1401Normal
SA242053N03-01_9_1_1407Normal
SA242054N01-02_7_1_1402Normal
SA242055N02-01_8_1_1404Normal
SA242056N01-03_7_1_1403Normal
SA242057N02-02_8_1_1405Normal
SA242058Prev1707-03-01_22_1_1446Preventative1707
SA242059Prev1707-03-02_22_1_1447Preventative1707
SA242060Prev1707-03-03_22_1_1448Preventative1707
SA242061Prev1707-02-03_21_1_1445Preventative1707
SA242062Prev1707-01-02_20_1_1441Preventative1707
SA242063Prev1707-01-01_20_1_1440Preventative1707
SA242064Prev1707-02-02_21_1_1444Preventative1707
SA242065Prev1707-01-03_20_1_1442Preventative1707
SA242066Prev1707-02-01_21_1_1443Preventative1707
SA242067Proph1707-02-03_29_1_1469Prophylactic1707
SA242068Proph1707-02-02_29_1_1468Prophylactic1707
SA242069Proph1707-01-01_28_1_1464Prophylactic1707
SA242070Proph1707-02-01_29_1_1467Prophylactic1707
SA242071Proph1707-01-02_28_1_1465Prophylactic1707
SA242072Proph1707-01-03_28_1_1466Prophylactic1707
SA242073Ther-1707-02-02_35_1_1486Therapeutic1707
SA242074Ther-1707-02-01_35_1_1485Therapeutic1707
SA242075Ther-1707-02-03_35_1_1487Therapeutic1707
SA242076Ther-1707-01-03_34_1_1484Therapeutic1707
SA242077Ther-1707-01-01_34_1_1482Therapeutic1707
SA242078Ther-1707-01-02_34_1_1483Therapeutic1707
SA242079Veh02-03_14_1_1424Vehicle
SA242080Veh02-02_14_1_1423Vehicle
SA242081Veh01-03_13_1_1421Vehicle
SA242082Veh01-01_13_1_1419Vehicle
SA242083Veh01-02_13_1_1420Vehicle
SA242084Veh02-01_14_1_1422Vehicle
Showing results 1 to 36 of 36
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