{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:34:52Z","timestamp":1792787692886,"version":"4.5.0"},"reference-count":97,"publisher":"SAGE Publications","issue":"13-15","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Melbourne School of Health Sciences at the University of Melbourne","id":[{"id":"https:\/\/ror.org\/01ej9dk98","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Medical Research Future Fund Stem Cell Therapies Mission","id":[{"id":"https:\/\/ror.org\/0513v5k17","id-type":"ROR","asserted-by":"crossref"}]},{"name":"School of Health Sciences at Swinburne University of Technology","id":[{"id":"https:\/\/ror.org\/031rekg67","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Friedreich ataxia Research Alliance"},{"name":"University of Wollongong","id":[{"id":"https:\/\/ror.org\/00jtmb277","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2026,11,1]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>\n                      Friedreich ataxia (FRDA) is a neurodegenerative disorder typically caused by autosomal recessive inheritance of expanded guanine\u2013adenine\u2013adenine (GAA) repeats (&gt;56) in both alleles of the frataxin (\n                      <jats:italic toggle=\"yes\">FXN<\/jats:italic>\n                      ) gene, leading to FXN protein deficiency. Omaveloxolone (Omav) is the only approved therapy. Therefore, further therapeutic options are essential. Previously, we showed that sulforaphane (SF) increases FXN expression and modulates epigenetic, inflammatory, and oxidative stress pathways in sensory neurons from a patient induced pluripotent stem cells (iPSCs) with 550 GAA1 repeats (FA2). Here, we compared SF, Omav, and dimethyl fumarate (DMF) treatment in sensory neurons derived from three patient iPSC lines with varying GAA1 repeats: FA1 (867), FA2, and FA3 (450).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>In FA1, SF treatment improved cell viability and reduced oxidative stress and inflammation. In FA3, SF increased cell viability, FXN protein levels, and gene and protein expression of redox markers, while targeting dysregulated epigenetic mechanisms and inflammation. All three lines showed SF\u2019s consistent anti-oxidant and anti-inflammatory effects. Responses to Omav and DMF varied across the FA lines with less pronounced effects than when treated with SF. Overall, SF was more effective than Omav and DMF in improving cell viability and regulating FXN expression and epigenetic, redox, and inflammatory pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation:<\/jats:title>\n                    <jats:p>These findings reveal variability in drug responses based on FRDA genetic profiles and position SF as a promising drug to address multiple pathological processes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      Our preclinical data support SF as a strong FRDA drug candidate. Clinical evaluation is warranted to confirm its full therapeutic potential.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      45, 561\u2013580.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15230864261470377","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T09:34:49Z","timestamp":1784540089000},"page":"561-580","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Unlocking Sulforaphane\u2019s Potential in Friedreich Ataxia: Further Evidence from Preclinical Investigations Using Induced Pluripotent Stem Cell-Derived Sensory Neurons"],"prefix":"10.1177","volume":"45","author":[{"given":"Wenyao","family":"Yang","sequence":"first","affiliation":[{"name":"School of Health Sciences, Swinburne University of Technology, Hawthorn, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Thompson","sequence":"additional","affiliation":[{"name":"Melbourne School of Health Sciences, The University of Melbourne, Parkville, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Miellet","sequence":"additional","affiliation":[{"name":"School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marnie","family":"Maddock","sequence":"additional","affiliation":[{"name":"School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Napierala","sequence":"additional","affiliation":[{"name":"Peter O\u2019Donnell Jr. Brain Institute, UT Southwestern Medical Center, Dallas, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirella","family":"Dottori","sequence":"additional","affiliation":[{"name":"School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9702-0563","authenticated-orcid":false,"given":"Faith A.A.","family":"Kwa","sequence":"additional","affiliation":[{"name":"School of Health Sciences, Swinburne University of Technology, Hawthorn, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00188"},{"key":"e_1_3_3_3_1","unstructured":"Applied Biosystems. High capacity cDNA reverse transcription kits user guide. 2018. Available from: https:\/\/assets.thermofisher.com\/TFS-Assets\/LSG\/manuals\/MAN0017977_highcap_cDNA_RT_UG.pdf [Last accessed: December13 2025]."},{"key":"e_1_3_3_4_1","unstructured":"Applied Biosystems. TaqMan\u2122 fast advanced master mix USER GUIDE. 2021. Available from: https:\/\/assets.thermofisher.com\/TFS-Assets\/LSG\/manuals\/MAN0025706_TaqManFastAdvMM_UG.pdf [Last accessed: December13 2025]."},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00099-20"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370219890873"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5254.1423"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt115"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2020.07.019"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104994"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0944-x"},{"key":"e_1_3_3_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/ldx034"},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27020502"},{"key":"e_1_3_3_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2019.104606"},{"key":"e_1_3_3_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.1.1"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaf190"},{"key":"e_1_3_3_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.805508"},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874467211666180125163009"},{"key":"e_1_3_3_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.614234"},{"key":"e_1_3_3_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000200234"},{"key":"e_1_3_3_21_1","unstructured":"FARA. Approved treatment. 2025a. Available from: https:\/\/www.curefa.org\/understanding-fa\/managing-fa\/approved-treatment\/ [Last accessed: December13 2025]."},{"key":"e_1_3_3_22_1","unstructured":"FARA. Omaveloxolone early compassionate access program now open in Australia! 2025b. Available from: https:\/\/www.fara.org.au\/news\/omaveloxolone-early-compassionate-access-program-now-open-in-australia [Last accessed: December13 2025]."},{"key":"e_1_3_3_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-022-03201-x"},{"key":"e_1_3_3_24_1","unstructured":"FACLR. Friedreich\u2019s ataxia cell line repository. 2025. Available from: https:\/\/labs.utsouthwestern.edu\/napierala-lab\/cell-line-repository [Last accessed: April18 2025]."},{"key":"e_1_3_3_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-023-01621-6"},{"key":"e_1_3_3_26_1","doi-asserted-by":"publisher","DOI":"10.2147\/DNND.S180027"},{"key":"e_1_3_3_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-019-00764-x"},{"key":"e_1_3_3_28_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2020.264"},{"key":"e_1_3_3_29_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/4564471"},{"key":"e_1_3_3_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-023-01574-x"},{"key":"e_1_3_3_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2021.11.015"},{"key":"e_1_3_3_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.600895"},{"key":"e_1_3_3_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29687"},{"key":"e_1_3_3_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0217776"},{"key":"e_1_3_3_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.952950"},{"key":"e_1_3_3_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1913416117"},{"key":"e_1_3_3_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.09.014"},{"key":"e_1_3_3_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2023.103718"},{"key":"e_1_3_3_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101791"},{"key":"e_1_3_3_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00356"},{"key":"e_1_3_3_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2019.101871"},{"key":"e_1_3_3_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-023-01874-9"},{"key":"e_1_3_3_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.827527"},{"key":"e_1_3_3_44_1","doi-asserted-by":"publisher","DOI":"10.1089\/bio.2015.0117"},{"key":"e_1_3_3_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.7392"},{"key":"e_1_3_3_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-025-13487-1"},{"key":"e_1_3_3_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics16091167"},{"key":"e_1_3_3_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0189990"},{"key":"e_1_3_3_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.679355"},{"key":"e_1_3_3_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51897"},{"key":"e_1_3_3_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29286"},{"key":"e_1_3_3_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25934"},{"key":"e_1_3_3_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.660"},{"key":"e_1_3_3_54_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2024.2310617"},{"key":"e_1_3_3_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15030718"},{"key":"e_1_3_3_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2022.175025"},{"key":"e_1_3_3_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2022.103385"},{"key":"e_1_3_3_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2019.03.022"},{"key":"e_1_3_3_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17954-3"},{"key":"e_1_3_3_60_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-024-03558-0"},{"key":"e_1_3_3_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2024.103477"},{"key":"e_1_3_3_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2024.103312"},{"key":"e_1_3_3_63_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy198"},{"key":"e_1_3_3_64_1","unstructured":"OLGA_Group. Prostaphane\u00ae: A formula developed in Brittany. 2015. Available from: https:\/\/www.prostaphane.com\/ [Last accessed: December31 2025]."},{"key":"e_1_3_3_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-022-05784-9"},{"key":"e_1_3_3_66_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1260977"},{"key":"e_1_3_3_67_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X19858888"},{"key":"e_1_3_3_68_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20205211"},{"key":"e_1_3_3_69_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18102173"},{"key":"e_1_3_3_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2023.12.002"},{"key":"e_1_3_3_71_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2023.2173063"},{"key":"e_1_3_3_72_1","unstructured":"Promega. CellTiter 96 AQueous one solution cell proliferation assay. 2023. Available from: https:\/\/www.promega.com.au\/products\/cell-health-assays\/cell-viability-and-cytotoxicity-assays\/celltiter-96-aqueous-one-solution-cell-proliferation-assay-_mts_\/?catNum=G3582#protocols [Last accessed: November23 2025]."},{"key":"e_1_3_3_73_1","unstructured":"Qiagen. RNA isolation and purification. 2025. Available from: https:\/\/www.qiagen.com\/us\/knowledge-and-support\/knowledge-hub\/bench-guide\/rna\/rna-purification\/rna-isolation-sample-source-considerations [Last accessed: April18 2025]."},{"key":"e_1_3_3_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2015.04.013"},{"key":"e_1_3_3_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(21)00027-2"},{"key":"e_1_3_3_76_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaa267"},{"key":"e_1_3_3_77_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000683"},{"key":"e_1_3_3_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-05472-z"},{"key":"e_1_3_3_79_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.30302"},{"key":"e_1_3_3_80_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200913"},{"key":"e_1_3_3_81_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10102383"},{"key":"e_1_3_3_82_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.606069"},{"key":"e_1_3_3_83_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.124.038505"},{"key":"e_1_3_3_84_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12242773"},{"key":"e_1_3_3_85_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins14060367"},{"key":"e_1_3_3_86_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-8-7"},{"key":"e_1_3_3_87_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678707.2016.1215910"},{"key":"e_1_3_3_88_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24260"},{"key":"e_1_3_3_89_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11051293"},{"key":"e_1_3_3_90_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcad020"},{"key":"e_1_3_3_91_1","doi-asserted-by":"publisher","DOI":"10.1089\/jmf.2018.0024"},{"key":"e_1_3_3_92_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.042317"},{"key":"e_1_3_3_93_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18122772"},{"key":"e_1_3_3_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-46678-8"},{"key":"e_1_3_3_95_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2024.0756"},{"key":"e_1_3_3_96_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2020.1821654"},{"key":"e_1_3_3_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.05.029"},{"key":"e_1_3_3_98_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-021-00447-5"}],"container-title":["Antioxidants &amp; Redox Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15230864261470377","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/15230864261470377","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15230864261470377","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:58:49Z","timestamp":1790564329000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/15230864261470377"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":97,"journal-issue":{"issue":"13-15","published-print":{"date-parts":[[2026,11,1]]}},"alternative-id":["10.1177\/15230864261470377"],"URL":"https:\/\/doi.org\/10.1177\/15230864261470377","relation":{},"ISSN":["1523-0864","1557-7716"],"issn-type":[{"value":"1523-0864","type":"print"},{"value":"1557-7716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]}}}