Please use this identifier to cite or link to this item:
http://bura.brunel.ac.uk/handle/2438/18519
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Jasoliya, M | - |
dc.contributor.author | Sacca, F | - |
dc.contributor.author | Sahdeo, S | - |
dc.contributor.author | Chedin, F | - |
dc.contributor.author | Pane, C | - |
dc.contributor.author | Brescia Morra, V | - |
dc.contributor.author | Filla, A | - |
dc.contributor.author | Pook, M | - |
dc.contributor.author | Cortopassi, G | - |
dc.date.accessioned | 2019-06-19T14:22:37Z | - |
dc.date.available | 2019-06-19T14:22:37Z | - |
dc.date.issued | 2019-06-03 | - |
dc.identifier | ORCID iD: Mark Pook https://orcid.org/0000-0003-1122-7748 | - |
dc.identifier | e0217776 | - |
dc.identifier.citation | Jasoliya, M. et al. (2019) 'Dimethyl fumarate dosing in humans increases frataxin expression: A potential therapy for Friedreich’s Ataxia', PloS ONE, 14 (6), e0217776, pp. 1 - 14. doi: 10.1371/journal.pone.0217776. | en_US |
dc.identifier.uri | https://bura.brunel.ac.uk/handle/2438/18519 | - |
dc.description | Data Availability Statement: All relevant data are within the manuscript and its Supporting Information files. | - |
dc.description.abstract | Friedreich’s Ataxia (FA) is an inherited neurodegenerative disorder resulting from decreased expression of the mitochondrial protein frataxin, for which there is no approved therapy. High throughput screening of clinically used drugs identified Dimethyl fumarate (DMF) as protective in FA patient cells. Here we demonstrate that DMF significantly increases frataxin gene (FXN) expression in FA cell model, FA mouse model and in DMF treated humans. DMF also rescues mitochondrial biogenesis deficiency in FA-patient derived cell model. We further examined the mechanism of DMF's frataxin induction in FA patient cells. It has been shown that transcription-inhibitory R-loops form at GAA expansion mutations, thus decreasing FXN expression. In FA patient cells, we demonstrate that DMF significantly increases transcription initiation. As a potential consequence, we observe significant reduction in both R-loop formation and transcriptional pausing thereby significantly increasing FXN expression. Lastly, DMF dosed Multiple Sclerosis (MS) patients showed significant increase in FXN expression by ~85%. Since inherited deficiency in FXN is the primary cause of FA, and DMF is demonstrated to increase FXN expression in humans, DMF could be considered for Friedreich's therapy. | en_US |
dc.description.sponsorship | FARA (Friedreich’s ataxia Research Alliance) and the NIH NS-077777; gift from the Packer-Wentz foundation. | en_US |
dc.format | Electronic-eCollection | - |
dc.format.extent | 1 - 14 | - |
dc.format.medium | Electronic | - |
dc.language | English | - |
dc.language.iso | en | en_US |
dc.publisher | Public Library of Science | en_US |
dc.rights | Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. | - |
dc.rights.uri | https://creativecommons.org/publicdomain/zero/1.0/ | - |
dc.title | Dimethyl fumarate dosing in humans increases frataxin expression: A potential therapy for Friedreich’s Ataxia | en_US |
dc.type | Article | en_US |
dc.identifier.doi | https://doi.org/10.1371/journal.pone.0217776 | - |
dc.relation.isPartOf | PloS one | - |
pubs.issue | 6 | - |
pubs.publication-status | Published | - |
pubs.volume | 14 | - |
dc.identifier.eissn | 1932-6203 | - |
dc.rights.holder | Jasoliya, M. et al | - |
Appears in Collections: | Dept of Life Sciences Research Papers |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
FullText.pdf | 1.41 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License