{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:46:06Z","timestamp":1790516766287,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,2,23]],"date-time":"2017-02-23T00:00:00Z","timestamp":1487808000000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/J012580\/1"],"award-info":[{"award-number":["MR\/J012580\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Friedreich's ataxia is a devastating neurological disease currently lacking any proven treatment. We studied the neuroprotective effects of the cytokines, granulocyte\u2010colony stimulating factor (G\u2010CSF) and stem cell factor (SCF) in a humanized murine model of Friedreich's ataxia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice received monthly subcutaneous infusions of cytokines while also being assessed at monthly time points using an extensive range of behavioral motor performance tests. After 6 months of treatment, neurophysiological evaluation of both sensory and motor nerve conduction was performed. Subsequently, mice were sacrificed for messenger RNA, protein, and histological analysis of the dorsal root ganglia, spinal cord, and cerebellum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cytokine administration resulted in significant reversal of biochemical, neuropathological, neurophysiological, and behavioural deficits associated with Friedreich's ataxia. Both G\u2010CSF and SCF had pronounced effects on frataxin levels (the primary molecular defect in the pathogenesis of the disease) and a regulators of frataxin expression. Sustained improvements in motor coordination and locomotor activity were observed, even after onset of neurological symptoms. Treatment also restored the duration of sensory nerve compound potentials. Improvements in peripheral nerve conduction positively correlated with cytokine\u2010induced increases in frataxin expression, providing a link between increases in frataxin and neurophysiological function. Abrogation of disease\u2010related pathology was also evident, with reductions in inflammation\/gliosis and increased neural stem cell numbers in areas of tissue injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>These experiments show that cytokines already clinically used in other conditions offer the prospect of a novel, rapidly translatable, disease\u2010modifying, and neuroprotective treatment for Friedreich's ataxia. Ann Neurol 2017;81:212\u2013226<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.24846","type":"journal-article","created":{"date-parts":[[2016,12,25]],"date-time":"2016-12-25T02:26:19Z","timestamp":1482632779000},"page":"212-226","source":"Crossref","is-referenced-by-count":29,"title":["Cytokine therapy\u2010mediated neuroprotection in a Friedreich's ataxia mouse model"],"prefix":"10.1002","volume":"81","author":[{"given":"Kevin C.","family":"Kemp","sequence":"first","affiliation":[{"name":"Multiple Sclerosis and Stem Cell Group, School of Clinical Sciences University of Bristol Bristol United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Cerminara","sequence":"additional","affiliation":[{"name":"Sensory and Motor Systems Group, School of Physiology, Pharmacology and Neuroscience University of Bristol Bristol United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Hares","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis and Stem Cell Group, School of Clinical Sciences University of Bristol Bristol United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Redondo","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis and Stem Cell Group, School of Clinical Sciences University of Bristol Bristol United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia J.","family":"Cook","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis and Stem Cell Group, School of Clinical Sciences University of Bristol Bristol United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry R.","family":"Haynes","sequence":"additional","affiliation":[{"name":"Brain Tumour Research Group, School of Clinical Sciences University of Bristol Bristol United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bronwen R.","family":"Burton","sequence":"additional","affiliation":[{"name":"Infection and Immunity, School of Cellular and Molecular Medicine University of Bristol Bristol United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Pook","sequence":"additional","affiliation":[{"name":"Synthetic Biology Theme, Institute of Environment, Health &amp; Societies, Biosciences, Dept. of Life Sciences, College of Health &amp; Life Sciences Brunel University London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Apps","sequence":"additional","affiliation":[{"name":"Sensory and Motor Systems Group, School of Physiology, Pharmacology and Neuroscience University of Bristol Bristol United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil J.","family":"Scolding","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis and Stem Cell Group, School of Clinical Sciences University of Bristol Bristol United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alastair","family":"Wilkins","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis and Stem Cell Group, School of Clinical Sciences University of Bristol Bristol United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,2,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.01.010"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/104.3.589"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5254.1423"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/301680"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.11.1771"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.009019"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12303"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-014-0184-7"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","first-page":"3378","DOI":"10.1182\/blood.V90.9.3378","article-title":"Enhanced levels and enhanced clonogenic capacity of blood progenitor cells following administration of stem cell factor plus granulocyte colony\u2010stimulating factor to humans","volume":"90","author":"Begley CG","year":"1997","journal-title":"Blood"},{"key":"e_1_2_8_11_1","first-page":"2491","article-title":"A randomized phase 3 study of peripheral blood progenitor cell mobilization with stem cell factor and filgrastim in high\u2010risk breast cancer patients","volume":"93","author":"Shpall EJ","year":"1999","journal-title":"Blood"},{"key":"e_1_2_8_12_1","doi-asserted-by":"crossref","first-page":"3422","DOI":"10.1182\/blood.V96.10.3422","article-title":"SCF and G\u2010CSF lead to the synergistic induction of proliferation and gene expression through complementary signaling pathways","volume":"96","author":"Duarte RF","year":"2000","journal-title":"Blood"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2006.12.001"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23559"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03319.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215251"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075562"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.563668"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017770"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2014.02.003"},{"key":"e_1_2_8_21_1","volume-title":"British national formulary: BNF.","author":"British Medical Association","year":"2015"},{"key":"e_1_2_8_22_1","first-page":"20","article-title":"The effect of short G\u2010CSF administration on the numbers and clonogenic efficiency of hematopoietic progenitor cells in bone marrow and peripheral blood of normal donors","volume":"5","author":"Zaucha JM","year":"2000","journal-title":"Ann Transplant"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.8.2736"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20101700"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.17"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2006.08.001"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2012.07.005"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws226"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2006.06.015"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0107416"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm271"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012286"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2014.08.043"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611133200"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.19.2061"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4537"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089488"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0317167100025518"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.66.1.93"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2014.143"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2003.028605"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3510"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60382-2"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-015-7719-2"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-015-2427-3"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.24066"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004253"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms14047853"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010025"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1515\/REVNEURO.1998.9.2.105"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-8-74"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1867"},{"key":"e_1_2_8_53_1","first-page":"124","article-title":"Mitochondrial dysfunction induced by frataxin deficiency is associated with cellular senescence and abnormal calcium metabolism","volume":"8","author":"Bolinches\u2010Amoros A","year":"2014","journal-title":"Front Cell Neurosci"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2011.07613.x"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-119073"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1702073"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.24846","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.24846","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T17:44:33Z","timestamp":1696009473000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.24846"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2]]},"references-count":55,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,2]]}},"alternative-id":["10.1002\/ana.24846"],"URL":"https:\/\/doi.org\/10.1002\/ana.24846","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2]]}}}