{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T09:08:51Z","timestamp":1779008931308,"version":"3.51.4"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100001594","name":"Dysautonomia Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001594","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Familial dysautonomia (FD) is a hereditary neurodevelopmental disorder caused by aberrant splicing of the\n                      <jats:italic>ELP1<\/jats:italic>\n                      gene, leading to a tissue\u2010specific reduction in ELP1 protein expression. Preclinical models indicate that increasing ELP1 levels can mitigate disease manifestations. A blood\u2010based ELP\u20101 protein assay may provide a reliable way to monitor gene target engagement.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and Methods<\/jats:title>\n                    <jats:p>Using a newly developed radioimmunoassay, we quantified ELP1 protein levels in peripheral blood samples collected from 59 homozygous FD patients carrying the IVS20\u2009+\u20096T&gt;C mutation and 66 heterozygous carriers. To assess the reproducibility of the measurement, replicate samples were collected in 43 participants. Longitudinal variability was evaluated in 22 participants who underwent repeat sampling 1\u2009year later.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ELP1 protein levels were significantly lower in FD patients compared to heterozygous carriers (244\u2009\u00b1\u200975 vs. 2210\u2009\u00b1\u20091031\u2009pg\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Replicate analysis of 43 paired samples showed strong consistency in ELP1 levels (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.000). Repeat measurements 1\u2009year after baseline showed longitudinal stability (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.827,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). An ELP1 threshold of 492\u2009pg\/mL yielded a sensitivity of 80.2% (CI of 70.6 to 87.2%) and a specificity of 98.2% (95% CI of 90%\u201399%) with a positive likelihood ratio of 46.5, indicating that individuals with FD were over 46 times more likely to have ELP1 levels below this threshold compared to non\u2010affected carriers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Blood ELP1 levels are robust and reproducible, with concentrations below 492\u2009pg\/mL strongly indicative of disease. Moreover, given their longitudinal stability, ELP1 can serve as a marker of target engagement to evaluate the efficacy of gene\u2010targeted therapies aimed at correcting ELP1 gene splicing and protein production.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70254","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T18:16:35Z","timestamp":1765563395000},"page":"942-947","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploratory Analysis of ELP1 Expression in Whole Blood From Patients With Familial Dysautonomia"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2434-9560","authenticated-orcid":false,"given":"Alejandra","family":"Gonz\u00e1lez\u2010Duarte","sequence":"first","affiliation":[{"name":"Department of Neurology New York University Grossman School of Medicine  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy","family":"Norcliffe\u2010Kaufmann","sequence":"additional","affiliation":[{"name":"Department of Neurology New York University Grossman School of Medicine  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Luisa","family":"Cotrina","sequence":"additional","affiliation":[{"name":"Department of Neurology New York University Grossman School of Medicine  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zenith","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Neurology New York University Grossman School of Medicine  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaia","family":"Dalamo","sequence":"additional","affiliation":[{"name":"Department of Neurology New York University Grossman School of Medicine  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricio Millar","family":"Vernetti","sequence":"additional","affiliation":[{"name":"Department of Neurology New York University Grossman School of Medicine  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Lawless","sequence":"additional","affiliation":[{"name":"Syneos Health  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Morini","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Salani","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marla","family":"Weetall","sequence":"additional","affiliation":[{"name":"PTC Therapeutics  Warren New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Narasimhan","sequence":"additional","affiliation":[{"name":"PTC Therapeutics  Warren New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agostino G.","family":"Rocha","sequence":"additional","affiliation":[{"name":"PTC Therapeutics  Warren New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan A.","family":"Slaugenhaupt","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Genomic Medicine Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Horacio","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Department of Neurology New York University Grossman School of Medicine  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.10499"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-023-00941-1"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2016.06.003"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.7247705"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.11.043"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181feb283"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhh.2011.107"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2012.10.012"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNO.0b013e318230feab"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-014-7258-2"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.02.009"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24705-5"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-45376-w"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.01.019"},{"key":"e_1_2_11_16_1","doi-asserted-by":"crossref","unstructured":"S.Yun 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