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| Status |
Public on Oct 26, 2022 |
| Title |
Circulating microRNAs in relapsing MS patients treated with dimethyl fumarate in the phase 4 TREMEND trial |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
Dimethyl fumarate (DMF) is an oral drug approved for relapsing multiple sclerosis (MS) that leads to reduction of neurofilament light (NFL). This may be related to dynamics and persistence of microRNA signatures in the peripheral blood of treatment-naïve MS patients before and after dimethyl fumarate (DMF) at different time points. 210 blood samples were collected from 51 treatment-naïve patients at baseline (BL) and after 1-3, 4-7, 9-15 and 21-27 months of DMF and from 22 controls from the phase IV TREMEND trial. Using microarray, 1,085 miRNAs were two-folds above the background and compared versus NFL. Altered miRNA profiles peaked after 4-7 months. MiR-16-5p and miR-4306, involved in the NF-kB-pathway, were upregulated in low NFL samples, while miR-940 and miR-4665-3p were upregulated in high NFL samples. NFL and miRNA correlations were strongest after 4-7 months DMF. In four patients with blood samples taken at all 5 time points, time-series analysis found miR-146a-5p, the inhibitor of the NF-kB-pathway, increased 1-3 months after treatment. DMF induces dynamic changes in composite miRNA profiles 4-7 months after initiation, several involved in the NF-kB-pathway. Upregulation of miR-16-5p and miR-4306 in low-NFL, while miR-940 and miR-4665-3p in high-NFL samples may indicate a response to DMF treatment.
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| Overall design |
210 blood samples from the TREMEND (Tecfidera in Relapsing-Remitting Multiple Sclerosis: Endothelial Dysfunction) phase IV clinical trial was divided into six different groups. Controls: blood 22 healthy controls. Baseline: 51 RRMS patients before Tecfidera (DMF) treatment. Early: 45 RRMS patients 1-3 month after DMF treatment. Intermediate: 20 RRMS patients 4-7 month after DMF treatment. 1-year: 49 RRMS patient after 1-year with DMF treatment. Long term: 23 RRMS patients 2 years after start of treatment with DMF. MicroRNA detections from RNA extracts of the whole blood samples were obtained with miRNA Microarray System.
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| Contributor(s) |
Elkjaer ML, Lohse RM, Burton M, Mendoza JP, Thomassen M, Sejbaek T, Illes Z |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Oct 13, 2022 |
| Last update date |
Oct 29, 2022 |
| Contact name |
Laura Catalini |
| E-mail(s) |
laura.catalini@studenti.unicam.it
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| Organization name |
Odense University Hospital
|
| Department |
Fertility clinic
|
| Street address |
Kløvervænget 23
|
| City |
Odense C |
| State/province |
Syddanmark |
| ZIP/Postal code |
DK-5000 |
| Country |
Denmark |
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| Platforms (1) |
| GPL25134 |
Agilent-070156 Human_miRNA_V21.0_Microarray 046064 (miRNA ID version) |
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| Samples (211)
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| Relations |
| BioProject |
PRJNA892969 |
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