{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:49:19Z","timestamp":1775868559544,"version":"3.50.1"},"reference-count":85,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lily Foundation","award":["LILY-2017.18 (APPLICATION 3 \u2013 BAX)"],"award-info":[{"award-number":["LILY-2017.18 (APPLICATION 3 \u2013 BAX)"]}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/K025406\/1"],"award-info":[{"award-number":["MR\/K025406\/1"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare disease for which there are currently no validated outcome measures for assessing therapeutic intervention efficacy. The aim of this study was to identify a plasma and\/or serum microRNA (miRNA) biomarker panel for MNGIE. Sixty-five patients and 65 age and sex matched healthy controls were recruited and assigned to one of four study phases: (i) discovery for sample size determination; (ii) candidate screening; (iii) candidate validation; and (iv) verifying the performance of the validated miRNA panel in four patients treated with erythrocyte-encapsulated thymidine phosphorylase (EE-TP), an enzyme replacement under development for MNGIE. Quantitative PCR (qPCR) was used to profile miRNAs in serum and\/or plasma samples collected for the discovery, validation and performance phases, and next generation sequencing (NGS) analysis was applied to serum samples assigned to the candidate screening phase. Forty-one differentially expressed candidate miRNAs were identified in the sera of patients (p &lt; 0.05, log2 fold change &gt; 1). The validation cohort revealed that of those, 27 miRNAs were upregulated in plasma and three miRNAs were upregulated in sera (p &lt; 0.05). Through binary logistic regression analyses, five plasma miRNAs (miR-192-5p, miR-193a-5p, miR-194-5p, miR-215-5p and miR-34a-5p) and three serum miRNAs (miR-192-5p, miR-194-5p and miR-34a-5p) were shown to robustly distinguish MNGIE from healthy controls. Reduced longitudinal miRNA expression of miR-34a-5p was observed in all four patients treated with EE-TP and coincided with biochemical and clinical improvements. We recommend the inclusion of the plasma exploratory miRNA biomarker panel in future clinical trials of investigational therapies for MNGIE; it may have prognostic value for assessing clinical status.<\/jats:p>","DOI":"10.3390\/ijms22073681","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T10:44:01Z","timestamp":1617273841000},"page":"3681","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Circulating miRNAs as Biomarkers for Mitochondrial Neuro-Gastrointestinal Encephalomyopathy"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2168-008X","authenticated-orcid":false,"given":"Mark","family":"Mencias","sequence":"first","affiliation":[{"name":"Molecular and Clinical Sciences, St. George\u2019s, University of London, London SW17 0RE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Levene","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences, St. George\u2019s, University of London, London SW17 0RE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6322-6571","authenticated-orcid":false,"given":"Kevin","family":"Blighe","sequence":"additional","affiliation":[{"name":"Clinical Bioinformatics Research Ltd., London W1B 3HH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6306-080X","authenticated-orcid":false,"given":"Bridget","family":"Bax","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences, St. George\u2019s, University of London, London SW17 0RE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the Project Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1212\/WNL.44.4.721","article-title":"Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE): Clinical, Biochemical, and Genetic Features of an Autosomal Recessive Mitochondrial Disorder","volume":"44","author":"Hirano","year":"1994","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1126\/science.283.5402.689","article-title":"Thymidine Phosphorylase Gene Mutations in MNGIE, a Human Mitochondrial Disorder","volume":"283","author":"Nishino","year":"1999","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0960-8966(00)00159-0","article-title":"MNGIE: From Nuclear DNA to Mitochondrial DNA","volume":"11","author":"Nishino","year":"2001","journal-title":"Neuromuscul. 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