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.

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	ST002416
Study Title	Proteomics and metabolomics of multiple sclerosis (Part 2)
Study Summary	Multiple 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 Name	Facility
First Name	Core
Address	M32, SIMR, College of Pharmacy, Health Sciences, University of Sharjah
Email	tims-tof@sharjah.ac.ae
Phone	065057656
Submit Date	2022-12-19
Raw Data Available	Yes
Raw Data File Type(s)	d
Analysis Type Detail	LC-MS
Release Date	2023-06-01
Release Version	1

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Treatment:

Treatment ID:	TR002517
Treatment Summary:	From Normal, EAE vehicle-treated, and therapeutic SIMR1707 treated mice, the cerebellum part of the brain was cut, and immediately snap frozen using liquid nitrogen. The samples then were weighed, made in powder form and homogenized using pistol method under liquid nitrogen. The cerebellum sample was lysed using 400 uL RIBA lysis buffer and let to set for 5-10 minutes to allow lysis. 50 ul of the homogenized sample was taken for RNA extraction using norgen biotek RNA/DNA purification kit (cat#:47700) according to the manufacturer’s instructions. The remaining 350 uL was processed for metabolites and proteins extraction. First, it was centrifuged for 5 minutes at 4 C, 13000 rpm. The supernatant was collected in a new 1.5 mL eppendorf tube. The supernatant was centrifuged again for 1 minute at 4 C, at maximum speed (>13000 rpm), and the supernatant was collected again in a new 1.5 mL tube and kept on ice as it was used in the following steps, while the pellet was discarded.

Treatment ID:

TR002517

Treatment Summary:

From Normal, EAE vehicle-treated, and therapeutic SIMR1707 treated mice, the cerebellum part of the brain was cut, and immediately snap frozen using liquid nitrogen. The samples then were weighed, made in powder form and homogenized using pistol method under liquid nitrogen. The cerebellum sample was lysed using 400 uL RIBA lysis buffer and let to set for 5-10 minutes to allow lysis. 50 ul of the homogenized sample was taken for RNA extraction using norgen biotek RNA/DNA purification kit (cat#:47700) according to the manufacturer’s instructions. The remaining 350 uL was processed for metabolites and proteins extraction. First, it was centrifuged for 5 minutes at 4 C, 13000 rpm. The supernatant was collected in a new 1.5 mL eppendorf tube. The supernatant was centrifuged again for 1 minute at 4 C, at maximum speed (>13000 rpm), and the supernatant was collected again in a new 1.5 mL tube and kept on ice as it was used in the following steps, while the pellet was discarded.