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MicroRNAs as potential biomarkers of response to modified Atkins diet in treatment of adults with drug-resistant epilepsy: A proof-of-concept study

2024-11-08Journal article Restricted access
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dc.contributor.authorSamões, Raquel
dc.contributor.authorCavalheiro, Ana
dc.contributor.authorSantos, Cristina
dc.contributor.authorLopes, Joana
dc.contributor.authorTeixeira, Catarina
dc.contributor.authorTavares, Maria Manuel
dc.contributor.authorCarvalho, Cláudia
dc.contributor.authorLemos, Carolina
dc.contributor.authorCosta, Paulo Pinho e
dc.contributor.authorCavaco, Sara
dc.contributor.authorChaves, João
dc.contributor.authorLeal, Bárbara
dc.date.accessioned2025-04-04T15:40:26Z
dc.date.available2025-04-04T15:40:26Z
dc.date.issued2024-11-08
dc.description.abstractBackground: Accurate predictors of response to modified Atkins diet (MAD) are needed. MicroRNAs are potential biomarkers in epilepsy. This study aimed to explore the value of circulating miR-146a, miR-155, miR-22, miR-21 and miR-134 levels in predicting response to MAD. Methods: Patients who completed 3 months of MAD were selected from a prospective cohort of adults with DRE followed in a specialized MAD outpatient clinic. Patients were classified as responders if any reduction in seizure frequency at follow-up, calculated through seizure-calendars). The >50 % seizure reduction cut-off was also explored. Qualitative benefits in seizures and cognition were analysed. Blood samples were collected prior to initiate MAD and microRNAs were quantified by qRT-PCR. Results: Thirty-nine patients were included (56 %males, mean age=33.1±8.5yo, 62 %focal epilepsies, 59 %structural aetiology): 20(51 %) were responders [mean reduction in seizure frequency=54 %(17-100 %); 10 had ≥50 % reduction]; 25(64 %) reported qualitative benefit in seizures and 21(54 %) reported cognitive benefits. At pre-treatment baseline, a panel combining serum levels of all studied microRNAs predicted seizure reduction (AUC=0.839, p<0.0001), qualitative benefit in seizures (AUC=0.683, p=0.048) and in cognition (AUC=0.751, p<0.01) at 3months. miR-146a was the only significant microRNA when evaluated in isolation. There was no statistical correlation in the biomarkers when a ≥50 % seizure reduction was compared to <50 %. Conclusions: A panel combining pre-treatment serum levels of miR-146a, miR-155, miR-134, miR-21 and miR-22 predicted any reduction in seizures with MAD in adults with DRE at 3months. This panel may be a promising biomarker and a useful tool in the selection of patients.por
dc.description.abstractHighlights: - A microRNA (miR) panel predicted response to modified Atkins diet in patients with epilepsy; - miR-146a were higher in patients with benefits in seizures and cognition; - miR-22 were higher in patients who reported improvement in cognition; - miR are promising biomarkers to select patients for treatment with modified Atkins diet.por
dc.description.sponsorshipLiga Portuguesa contra a Epilepsia 2020 scientific grant; Centro Hospitalar Universitário do Porto 2020 grant for investigation projects; Unit for Multidisciplinary Research in Biomedicine (UMIB) is funded by FCT Portugal (grant numbers UIDB/00215/2020, and UIDP/00215/2020), and Laboratory for Integrative and Translational Research in Population Health (ITR) (LA/P/0064/2020); BICE Tecnifar grant
dc.identifier.citationEpilepsy Res. 2024 Dec:208:107478. doi: 10.1016/j.eplepsyres.2024.107478. Epub 2024 Nov 8
dc.identifier.doi10.1016/j.eplepsyres.2024.107478
dc.identifier.issn0920-1211
dc.identifier.pmid39536682
dc.identifier.urihttp://hdl.handle.net/10400.18/10488
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier
dc.relationUnit for Multidisciplinary Research in Biomedicine
dc.relationLaboratory for Integrative and Translational Research in Population Health
dc.relation.hasversionhttps://www.sciencedirect.com/science/article/pii/S0920121124001931?via%3Dihub
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectDrug Response Biomarkers
dc.subjectInflammation
dc.subjectKetogenic Diet
dc.subjectMechanism of Action
dc.subjectDoenças Genéticas
dc.titleMicroRNAs as potential biomarkers of response to modified Atkins diet in treatment of adults with drug-resistant epilepsy: A proof-of-concept studypor
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleUnit for Multidisciplinary Research in Biomedicine
oaire.awardTitleLaboratory for Integrative and Translational Research in Population Health
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F00215%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0064%2F2020/PT
oaire.citation.startPage107478
oaire.citation.titleEpilepsy Research
oaire.citation.volume208
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
relation.isProjectOfPublication3b59bbc6-7ac7-4600-b3e8-58aab73d3816
relation.isProjectOfPublication18ca3cb0-ef66-4dd8-b45e-4cb0654cd7e8
relation.isProjectOfPublication.latestForDiscovery3b59bbc6-7ac7-4600-b3e8-58aab73d3816

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