{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:25:05Z","timestamp":1790835905101,"version":"4.1.0"},"reference-count":19,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec id=\"abs1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Polyamine levels are intricately controlled by biosynthetic, catabolic enzymes and antizymes. The complexity suggests that minute alterations in levels lead to profound abnormalities. We described the therapeutic course for a rare syndrome diagnosed by whole exome sequencing caused by gain-of-function variants in the C-terminus of ornithine decarboxylase (ODC), characterized by neurological deficits and alopecia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs2\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      <jats:italic>N-<\/jats:italic>\n                      acetylputrescine levels with other metabolites were measured using ultra-performance liquid chromatography paired with mass spectrometry and Z-scores established against a reference cohort of 866 children.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs3\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>From previous studies and metabolic profiles, eflornithine was identified as potentially beneficial with therapy initiated on FDA approval. Eflornithine normalized polyamine levels without disrupting other pathways. She demonstrated remarkable improvement in both neurological symptoms and cortical architecture. She gained fine motor skills with the capacity to feed herself and sit with support.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs4\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>This work highlights the strategy of repurposing drugs to treat a rare disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs5\">\n                    <jats:title>Funding:<\/jats:title>\n                    <jats:p>No external funding was received for this work.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7554\/elife.67097","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T20:00:31Z","timestamp":1626724831000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.67097","source":"Crossref","is-referenced-by-count":37,"title":["Repurposing eflornithine to treat a patient with a rare ODC1 gain-of-function variant disease"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4430-006X","authenticated-orcid":true,"given":"Surender","family":"Rajasekaran","sequence":"first","affiliation":[{"name":"Pediatric Critical Care Medicine, Helen DeVos Children\u2019s Hospital, Grand Rapids, United States"},{"name":"Spectrum Health Office of Research and Education, Grand Rapids, United States"},{"name":"Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb P","family":"Bupp","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, United States"},{"name":"Medical Genetics, Spectrum Health and Helen DeVos Children\u2019s Hospital, Grand Rapids, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Leimanis-Laurens","sequence":"additional","affiliation":[{"name":"Pediatric Critical Care Medicine, Helen DeVos Children\u2019s Hospital, Grand Rapids, United States"},{"name":"Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankit","family":"Shukla","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Helen DeVos Children\u2019s Hospital, Grand Rapids, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Russell","sequence":"additional","affiliation":[{"name":"Spectrum Health Office of Research and Education, Grand Rapids, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Junewick","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology, Spectrum Health and Helen DeVos Children's Hospital, Grand Rapids, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Gleason","sequence":"additional","affiliation":[{"name":"Spectrum Health Office of Research and Education, Grand Rapids, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5504-9248","authenticated-orcid":true,"given":"Elizabeth A","family":"VanSickle","sequence":"additional","affiliation":[{"name":"Medical Genetics, Spectrum Health and Helen DeVos Children\u2019s Hospital, Grand Rapids, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Edgerly","sequence":"additional","affiliation":[{"name":"Spectrum Health Office of Research and Education, Grand Rapids, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan M","family":"Wittmann","sequence":"additional","affiliation":[{"name":"Metabolon, Morrisville, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy W","family":"Prokop","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, United States"},{"name":"Department of Pharmacology and Toxicology, College of Human Medicine, Michigan State University, East Lansing, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 S","family":"Bachmann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,7,20]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1093\/cid\/cis886","article-title":"Nifurtimox-Eflornithine Combination Therapy for Second-Stage Gambiense Human African Trypanosomiasis: M\u00e9decins Sans Fronti\u00e8res Experience in the Democratic Republic of the Congo","volume":"56","author":"Alirol","year":"2013","journal-title":"Clinical Infectious Diseases"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1177\/0883073813495959","article-title":"Clinical trials in rare disease: challenges and opportunities","volume":"28","author":"Augustine","year":"2013","journal-title":"Journal of Child Neurology"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"7804","DOI":"10.1073\/pnas.90.16.7804","article-title":"The ornithine decarboxylase gene is a transcriptional target of c-Myc","volume":"90","author":"Bello-Fernandez","year":"1993","journal-title":"PNAS"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"2548","DOI":"10.1002\/ajmg.a.40523","article-title":"Novel de novo pathogenic variant in the ODC1 gene in a girl with developmental delay, alopecia, and dysmorphic features","volume":"176","author":"Bupp","year":"2018","journal-title":"American Journal of Medical Genetics Part A"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.ymgme.2008.10.003","article-title":"Clinical research for rare disease: Opportunities, challenges, and solutions","volume":"96","author":"Griggs","year":"2009","journal-title":"Molecular Genetics and Metabolism"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1038\/s41586-019-1076-8","article-title":"Precise therapeutic gene correction by a simple nuclease-induced double-stranded break","volume":"568","author":"Iyer","year":"2019","journal-title":"Nature"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1056\/NEJMoa1706198","article-title":"Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy","volume":"377","author":"Mendell","year":"2017","journal-title":"New England Journal of Medicine"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1158\/1940-6207.CAPR-08-0042","article-title":"Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: a randomized placebo-controlled, double-blind trial","volume":"1","author":"Meyskens","year":"2008","journal-title":"Cancer Prevention Research"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/s41431-019-0508-0","article-title":"Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database","volume":"28","author":"Nguengang Wakap","year":"2020","journal-title":"European Journal of Human Genetics"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"6549","DOI":"10.1128\/MCB.21.19.6549-6558.2001","article-title":"The ornithine decarboxylase gene is essential for cell survival during early murine development","volume":"21","author":"Pendeville","year":"2001","journal-title":"Molecular and Cellular Biology"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/S0140-6736(09)61117-X","article-title":"Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial","volume":"374","author":"Priotto","year":"2009","journal-title":"The Lancet"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"2554","DOI":"10.1002\/ajmg.a.60677","article-title":"Gain-of-function variants in the ODC1 gene cause a syndromic neurodevelopmental disorder associated with macrocephaly, alopecia, dysmorphic features, and neuroimaging abnormalities","volume":"176","author":"Rodan","year":"2018","journal-title":"American Journal of Medical Genetics Part A"},{"key":"bib13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0127246","article-title":"A phase I trial of DFMO targeting polyamine addiction in patients with relapsed\/refractory neuroblastoma","volume":"10","author":"Saulnier Sholler","year":"2015","journal-title":"PLOS ONE"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"2047","DOI":"10.1042\/BCJ20190294","article-title":"Biochemical features of primary cells from a pediatric patient with a gain-of-function ODC1 genetic mutation","volume":"476","author":"Schultz","year":"2019","journal-title":"Biochemical Journal"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1111\/1523-1747.ep12340155","article-title":"Modulation of murine hair follicle function by alterations in ornithine decarboxylase activity","volume":"106","author":"Soler","year":"1996","journal-title":"Journal of Investigative Dermatology"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"2131","DOI":"10.1056\/NEJMoa1714458","article-title":"Effect of genetic diagnosis on patients with previously undiagnosed disease","volume":"379","author":"Splinter","year":"2018","journal-title":"New England Journal of Medicine"},{"key":"bib17","doi-asserted-by":"publisher","DOI":"10.32113\/cellr4_20198_2735","article-title":"A case of a mild wolfram syndrome with concomitant ATP7B mutation","volume":"7","author":"Squitti","year":"2019","journal-title":"CellR4"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"2246","DOI":"10.1056\/NEJMoa1515792","article-title":"Exome sequencing and the management of neurometabolic disorders","volume":"374","author":"Tarailo-Graovac","year":"2016","journal-title":"New England Journal of Medicine"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/s41586-020-2434-2","article-title":"Whole-genome sequencing of patients with rare diseases in a national health system","volume":"583","author":"Turro","year":"2020","journal-title":"Nature"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/67097\/elife-67097-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/67097\/elife-67097-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/67097","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:12:22Z","timestamp":1697058742000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/67097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,20]]},"references-count":19,"alternative-id":["10.7554\/eLife.67097"],"URL":"https:\/\/doi.org\/10.7554\/elife.67097","archive":["CLOCKSS"],"relation":{"has-review":[{"id-type":"doi","id":"10.7554\/eLife.67097.sa2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.67097.sa1","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,20]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e67097"}}