{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:21:31Z","timestamp":1792178491807,"version":"4.4.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100005632","name":"Narodowe Centrum Bada\u0144 i Rozwoju","doi-asserted-by":"publisher","award":["STRATEGMED1\/233368\/1\/NCBR\/2014"],"award-info":[{"award-number":["STRATEGMED1\/233368\/1\/NCBR\/2014"]}],"id":[{"id":"10.13039\/501100005632","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BioDrugs"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1007\/s40259-020-00462-7","type":"journal-article","created":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T06:14:51Z","timestamp":1609827291000},"page":"47-60","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Administration of CD4+CD25highCD127\u2212FoxP3+ Regulatory T Cells for Relapsing-Remitting Multiple Sclerosis: A Phase 1 Study"],"prefix":"10.1007","volume":"35","author":[{"given":"Kamil","family":"Chwojnicki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Iwaszkiewicz-Grze\u015b","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Jankowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Zieli\u0144ski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"\u0141owiec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"Gliwi\u0144ski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Grzywi\u0144ska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamil","family":"Kowalczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Konarzewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Glasner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna","family":"Sakowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Kulczycka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Ja\u017awi\u0144ska-Cury\u0142\u0142o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlena","family":"Kubach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartosz","family":"Karaszewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walenty","family":"Nyka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edyta","family":"Szurowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5287-5210","authenticated-orcid":false,"given":"Piotr","family":"Trzonkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,5]]},"reference":[{"key":"462_CR1","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1038\/nri3871","volume":"15","author":"CA Dendrou","year":"2015","unstructured":"Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol. 2015;15:545.","journal-title":"Nat Rev Immunol"},{"key":"462_CR2","first-page":"879","volume":"113","author":"J Havla","year":"2016","unstructured":"Havla J, Warnke C, Derfuss T, Kappos L, Hartung HP, Hohlfeld R. Interdisciplinary risk management in the treatment of multiple sclerosis. Dtsch Arztebl Int. 2016;113:879\u201386.","journal-title":"Dtsch Arztebl Int."},{"key":"462_CR3","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/ni.2554","volume":"14","author":"AK Abbas","year":"2013","unstructured":"Abbas AK, Benoist C, Bluestone JA, Campbell DJ, Ghosh S, Hori S, Jiang S, Kuchroo VK, Mathis D, Roncarolo MG, Rudensky A, Sakaguchi S, Shevach EM, Vignali DA, Ziegler SF. Regulatory T cells: recommendations to simplify the nomenclature. Nat Immunol. 2013;14:307\u20138.","journal-title":"Nat Immunol"},{"key":"462_CR4","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1111\/imr.12169","volume":"259","author":"M Kleinewietfeld","year":"2014","unstructured":"Kleinewietfeld M, Hafler DA. Regulatory T cells in autoimmune neuroinflammation. Immunol Rev. 2014;259:231\u201344.","journal-title":"Immunol Rev"},{"key":"462_CR5","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1038\/nri2785","volume":"10","author":"S Sakaguchi","year":"2010","unstructured":"Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol. 2010;10:490\u2013500.","journal-title":"Nat Rev Immunol"},{"key":"462_CR6","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1016\/j.autrev.2011.05.004","volume":"10","author":"M Miyara","year":"2011","unstructured":"Miyara M, Gorochov G, Ehrenstein M, Musset L, Sakaguchi S, Amoura Z. Human FoxP3+ regulatory T cells in systemic autoimmune diseases. Autoimmun Rev. 2011;10:744\u201355.","journal-title":"Autoimmun Rev"},{"key":"462_CR7","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1002\/cyto.a.20659","volume":"75","author":"P Trzonkowski","year":"2009","unstructured":"Trzonkowski P, Szmit E, My\u015bliwska J, My\u015bliwski A. Ex vivo expansion of CD4(+)CD25(+) T regulatory cells for immunosuppressive therapy. Cytometry A. 2009;75:175\u201388.","journal-title":"Cytometry A"},{"key":"462_CR8","doi-asserted-by":"publisher","first-page":"2507","DOI":"10.4049\/jimmunol.1500801","volume":"195","author":"DJ Campbell","year":"2015","unstructured":"Campbell DJ. Control of regulatory T cell migration, function, and homeostasis. J Immunol. 2015;195:2507\u201313.","journal-title":"J Immunol"},{"key":"462_CR9","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/s40259-017-0228-3","volume":"31","author":"M Gliwi\u0144ski","year":"2017","unstructured":"Gliwi\u0144ski M, Iwaszkiewicz-Grze\u015b D, Trzonkowski P. Cell-based therapies with T regulatory cells. BioDrugs. 2017;31:335\u201347.","journal-title":"BioDrugs"},{"key":"462_CR10","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1126\/scitranslmed.aaa7721","volume":"7","author":"P Trzonkowski","year":"2015","unstructured":"Trzonkowski P, Bacchetta R, Battaglia M, Berglund D, Bohnenkamp HR, ten Brinke A, Bushell A, Cools N, Geissler EK, Gregori S, Marieke van Ham S, Hilkens C, Hutchinson JA, Lombardi G, Madrigal JA, Marek-Trzonkowska N, Martinez-Caceres EM, Roncarolo MG, Sanchez-Ramon S, Saudemont A, Sawitzki B. Hurdles in therapy with regulatory T cells. Sci Transl Med. 2015;7:304\u201318.","journal-title":"Sci Transl Med"},{"key":"462_CR11","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.clim.2009.06.001","volume":"133","author":"P Trzonkowski","year":"2009","unstructured":"Trzonkowski P, Bieniaszewska M, Ju\u015bci\u0144ska J, Dobyszuk A, Krzystyniak A, Marek N, My\u015bliwska J, Hellmann A. First-in-man clinical results of the treatment of patients with graft versus host disease with human ex vivo expanded CD4+CD25+CD127- T regulatory cells. Clin Immunol. 2009;133:22\u20136.","journal-title":"Clin Immunol"},{"key":"462_CR12","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.2337\/dc12-0038","volume":"35","author":"N Marek-Trzonkowska","year":"2012","unstructured":"Marek-Trzonkowska N, My\u015bliwiec M, Dobyszuk A, Grabowska M, Techmanska I, Juscinska J, Wujtewicz MA, Witkowski P, Mlynarski W, Balcerska A, Mysliwska J, Trzonkowski P. Administration of CD4+CD25highCD127- regulatory T cells preserves \u03b2-cell function in type 1 diabetes in children. Diabetes Care. 2012;35:1817\u201320.","journal-title":"Diabetes Care"},{"key":"462_CR13","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1186\/s12967-016-1090-7","volume":"14","author":"N Marek-Trzonkowska","year":"2016","unstructured":"Marek-Trzonkowska N, My\u015bliwiec M, Iwaszkiewicz-Grze\u015b D, Gliwi\u0144ski M, Derkowska I, \u017bali\u0144ska M, Zieli\u0144ski M, Grabowska M, Zieli\u0144ska H, Piekarska K, Ja\u017awi\u0144ska-Cury\u0142\u0142o A, Owczuk R, Szadkowska A, Wyka K, Witkowski P, M\u0142ynarski W, Jarosz-Chobot P, Bossowski A, Siebert J, Trzonkowski P. Factors affecting long-term efficacy of T regulatory cell-based therapy in type 1 diabetes. J Transl Med. 2016;14:332.","journal-title":"J Transl Med"},{"key":"462_CR14","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.clim.2014.03.016","volume":"153","author":"N Marek-Trzonkowska","year":"2014","unstructured":"Marek-Trzonkowska N, My\u015bliwiec M, Dobyszuk A, Grabowska M, Derkowska I, Ju\u015bci\u0144ska J, Owczuk R, Szadkowska A, Witkowski P, M\u0142ynarski W, Jarosz-Chobot P, Bossowski A, Siebert J, Trzonkowski P. Therapy of type 1 diabetes with CD4+CD25highCD127- regulatory T cells prolongs survival of pancreatic islets\u2014results of one year follow-up. Clin Immunol. 2014;153:23\u201330.","journal-title":"Clin Immunol"},{"key":"462_CR15","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.3727\/096368911X566217","volume":"11\u201312","author":"N Marek","year":"2011","unstructured":"Marek N, Bieniaszewska M, Krzystyniak A, Juscinska J, Mysliwska J, Witkowski P, Hellmann A, Trzonkowski P. The time is crucial for ex vivo expansion of T regulatory cells for therapy. Cell Transplant. 2011;11\u201312:1747\u201358.","journal-title":"Cell Transplant"},{"key":"462_CR16","doi-asserted-by":"publisher","first-page":"2326","DOI":"10.1523\/JNEUROSCI.1815-18.2019","volume":"39","author":"SS Duffy","year":"2011","unstructured":"Duffy SS, Keating BA, Perera CJ, Lees JG, Tonkin RS, Makker PGS, Carrive P, Butovsky O, Moalem-Taylor G. Regulatory T cells and their derived cytokine, interleukin-35, reduce pain in experimental autoimmune encephalomyelitis. J Neurosci. 2011;39:2326\u201346.","journal-title":"J Neurosci."},{"key":"462_CR17","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1002\/ana.1032","volume":"50","author":"WI McDonald","year":"2001","unstructured":"McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121\u20137.","journal-title":"Ann Neurol"},{"key":"462_CR18","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1002\/ana.22366","volume":"69","author":"CH Polman","year":"2011","unstructured":"Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O\u2019Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69:292\u2013302.","journal-title":"Ann Neurol."},{"key":"462_CR19","unstructured":"European Medicinal Agency (2005) Guideline on clinical trials in small populations. CHMP\/EWP\/83561\/2005s. https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-clinical-trials-small-populations_en.pdf. Accessed 14 Dec 2020"},{"key":"462_CR20","unstructured":"Clinical Study Measures. National Multiple Sclerosis Society. https:\/\/www.nationalmssociety.org\/For-Professionals\/Researchers\/Resources-for-Researchers\/Clinical-Study-Measures.  Accessed 14 Dec 2020"},{"key":"462_CR21","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1212\/WNL.33.11.1444","volume":"33","author":"JF Kurtzke","year":"1983","unstructured":"Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33:1444\u201352.","journal-title":"Neurology"},{"key":"462_CR22","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1177\/135245859900500409","volume":"5","author":"JS Fischer","year":"1999","unstructured":"Fischer JS, Rudick RA, Cutter GR, Reingold SC, for the National MS Society Clinical Outcomes Assessment Task Force. The multiple sclerosis functional composite measure (MSFC): an integrated approach to MS clinical outcome assessment. Multiple Sclerosis. 1999;5:244\u201350.","journal-title":"Multiple Sclerosis"},{"key":"462_CR23","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/0168-8510(90)90421-9","volume":"16","author":"EuroQol Group","year":"1990","unstructured":"EuroQol Group. EuroQol\u2014a new facility for the measurement of health-related quality of life. Health Policy. 1990;16:199\u2013208.","journal-title":"Health Policy"},{"key":"462_CR24","first-page":"597","volume":"11","author":"MP Wattjes","year":"2015","unstructured":"Wattjes MP, Rovira \u00c0, Miller D, Yousry TA, Sormani MP, de Stefano MP, Tintor\u00e9 M, Auger C, Tur C, Filippi M, Rocca MA, Fazekas F, Kappos L, Polman C, Barkhof F, Xavier M, MAGNIMS study group. Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis\u2013establishing disease prognosis and monitoring patients. Nat Rev Neurol. 2015;11:597\u2013606.","journal-title":"Nat Rev Neurol."},{"key":"462_CR25","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1038\/nrneurol.2015.106","volume":"11","author":"\u00c0 Rovira","year":"2015","unstructured":"Rovira \u00c0, Wattjes MP, Tintor\u00e9 M, Tur C, Yousry TA, Sormani MP, De Stefano N, Filippi M, Auger C, Rocca MA, Barkhof F, Fazekas F, Kappos L, Polman C, Miller D, Montalban X, MAGNIMS study group. Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-clinical implementation in the diagnostic process. Nat Rev Neurol. 2015;11:471\u201382.","journal-title":"Nat Rev Neurol."},{"key":"462_CR26","doi-asserted-by":"publisher","first-page":"3433","DOI":"10.4049\/jimmunol.0904028","volume":"184","author":"AM Thornton","year":"2010","unstructured":"Thornton AM, Korty PE, Tran DQ, Wohlfert EA, Murray PE, Belkaid Y, Shevach EM. Expression of helios, an ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J Immunol. 2010;184:3433\u20138.","journal-title":"J Immunol"},{"key":"462_CR27","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1038\/nature10251","volume":"476","author":"International Multiple Sclerosis Genetics Consortium","year":"2011","unstructured":"International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 2011;476:214\u20139.","journal-title":"Nature"},{"key":"462_CR28","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.4049\/jimmunol.1001543","volume":"187","author":"K Raddassi","year":"2011","unstructured":"Raddassi K, Kent SC, Yang J, Bourcier K, Bradshaw EM, Seyfert-Margolis V, Nepom GT, Kwok WW, Hafler DA. Increased frequencies of myelin oligodendrocyte glycoprotein\/MHC class II-binding CD4 cells in patients with multiple sclerosis. J Immunol. 2011;187:1039.","journal-title":"J Immunol"},{"key":"462_CR29","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1172\/JCI58649","volume":"122","author":"A Nylander","year":"2012","unstructured":"Nylander A, Hafler DA. Multiple sclerosis. J Clin Investig. 2012;122:1180\u20138.","journal-title":"J Clin Investig"},{"key":"462_CR30","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1093\/intimm\/dxh029","volume":"16","author":"X Zhang","year":"2004","unstructured":"Zhang X, Koldzic DN, Izikson L, Reddy J, Nazareno RF, Sakaguchi S, Kuchroo VK, Weiner HL. IL-10 is involved in the suppression of experimental autoimmune encephalomyelitis by CD25+CD4+ regulatory T cells. Int Immunol. 2004;16:249\u201356.","journal-title":"Int Immunol"},{"key":"462_CR31","doi-asserted-by":"publisher","first-page":"3343","DOI":"10.1002\/eji.200526065","volume":"35","author":"J Haas","year":"2005","unstructured":"Haas J, Hug A, Vieh\u00f6ver A, Fritzsching B, Falk CS, Filser A, Vetter T, Milkova L, Korporal M, Fritz B, Storch-Hagenlocher B, Krammer PH, Suri-Payer E, Wildemann B. Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis. Eur J Immunol. 2005;35:3343\u201352.","journal-title":"Eur J Immunol"},{"key":"462_CR32","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1002\/jnr.20852","volume":"83","author":"K Venken","year":"2006","unstructured":"Venken K, Hellings N, Hensen K, Rummens JL, Medaer R, Dhooghe MB, Dubois B, Raus J, Stinissen P. Secondary progressive in contrast to relapsing-remitting multiple sclerosis patients show a normal CD4+CD25+ regulatory T-cell function and FOXP3 expression. J Neurosci Res. 2006;83:1432\u201346.","journal-title":"J Neurosci Res"},{"key":"462_CR33","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1111\/j.1365-2249.2006.03271.x","volume":"147","author":"U Feger","year":"2007","unstructured":"Feger U, Luther C, Poeschel S, Melms A, Tolosa E, Wiendl H. Increased frequency of CD4+ CD25+ regulatory T cells in the cerebrospinal fluid but not in the blood of multiple sclerosis patients. Clin Exp Immunol. 2007;147:412\u20138.","journal-title":"Clin Exp Immunol"},{"key":"462_CR34","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s13024-016-0116-1","volume":"11","author":"MJ Lee","year":"2016","unstructured":"Lee MJ, Bing SJ, Choi J, Jang M, Lee G, Lee H, Chang BS, Jee Y, Lee SJ, Cho IH. IKK\u03b2-mediated inflammatory myeloid cell activation exacerbates experimental autoimmune encephalomyelitis by potentiating Th1\/Th17 cell activation and compromising blood brain barrier. Mol Neurodegener. 2016;11:54.","journal-title":"Mol Neurodegener"},{"key":"462_CR35","doi-asserted-by":"publisher","first-page":"4260","DOI":"10.1182\/blood-2006-06-027409","volume":"108","author":"PER Hoffmann","year":"2006","unstructured":"Hoffmann PER, Boeld TJ, Doser K, Piseshka B, Andreesen R, Edinger M. Only the CD45RA+ subpopulation of CD4+CD25high T cells gives rise to homogeneous regulatory T-cell lines upon in vitro expansion. Blood. 2006;108:4260\u20137.","journal-title":"Blood"},{"key":"462_CR36","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1111\/imr.12160","volume":"259","author":"EM Shevach","year":"2014","unstructured":"Shevach EM, Thornton AM. tTregs, pTregs, and iTregs: similarities and differences. Immunol Rev. 2014;259:88\u2013102.","journal-title":"Immunol Rev"},{"key":"462_CR37","doi-asserted-by":"publisher","first-page":"2966","DOI":"10.1002\/eji.200940030","volume":"39","author":"MHP Edinger","year":"2009","unstructured":"Edinger MHP. Regulatory T cells for the prevention of graft-versus-host disease: professionals defeat amateurs. Eur J Immunol. 2009;39:2966\u20138.","journal-title":"Eur J Immunol"},{"key":"462_CR38","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1212\/WNL.43.4.655","volume":"43","author":"The IFNB Multiple Sclerosis Study Group","year":"1993","unstructured":"The IFNB Multiple Sclerosis Study Group. Interferon \u03b2-1b is effective in relapsing-remitting multiple sclerosis: I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology. 1993;43:655\u201361.","journal-title":"Neurology"},{"key":"462_CR39","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1212\/WNL.45.7.1277","volume":"45","author":"The IFNB Multiple Sclerosis Study Group and The University of British Columbia MS\/MRI Analysis Group","year":"1995","unstructured":"The IFNB Multiple Sclerosis Study Group and The University of British Columbia MS\/MRI Analysis Group. Interferon \u03b2-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. Neurology. 1995;45:1277\u201385.","journal-title":"Neurology"},{"key":"462_CR40","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1212\/WNL.41.4.533","volume":"41","author":"MB Bornstein","year":"1991","unstructured":"Bornstein MB, Miller AI, Slagle S. A placebo controlled, double blinded, randomized, two-center, pilot trial of Cop 1 in chronic progressive multiple sclerosis. Neurology. 1991;41:533\u20139.","journal-title":"Neurology"},{"key":"462_CR41","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.1007\/s00415-013-6954-7","volume":"260","author":"A Bar-Or","year":"2013","unstructured":"Bar-Or A, Gold R, Kappos L, Arnold DL, Giovannoni G, Selmaj K, O\u2019Gorman J, Stephan M, Dawson KT. Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: subgroup analyses of the DEFINE study. J Neurol. 2013;260:2297\u2013305.","journal-title":"J Neurol."},{"key":"462_CR42","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1056\/NEJM198708133170703","volume":"317","author":"MB Bornstein","year":"1987","unstructured":"Bornstein MB, Miller A, Slagle S, Weitzman M, Crystal H, Drexler E, Keilson M, Merriam A, Wassertheil-Smoller S, Spada V. A pilot trial of Cop 1 in exacerbating-remitting multiple sclerosis. N Engl J Med. 1987;317:408\u201314.","journal-title":"N Engl J Med."},{"key":"462_CR43","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1056\/NEJMoa1206328","volume":"367","author":"RJ Fox","year":"2012","unstructured":"Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, Yang M, Raghupathi K, Novas M, Sweetser MT, Viglietta V, Dawson KT, CONFIRM Study Investigators. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med. 2012;367:1087\u201397.","journal-title":"N Engl J Med."}],"container-title":["BioDrugs"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40259-020-00462-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s40259-020-00462-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40259-020-00462-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T14:31:47Z","timestamp":1610548307000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s40259-020-00462-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["462"],"URL":"https:\/\/doi.org\/10.1007\/s40259-020-00462-7","relation":{},"ISSN":["1173-8804","1179-190X"],"issn-type":[{"value":"1173-8804","type":"print"},{"value":"1179-190X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"5 December 2020","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 January 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was supported by the National Centre for Research and Development, Poland (grant no STRATEGMED1\/233368\/1\/NCBR\/2014 to PT).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"PT and KC are co-inventors of patents related to the presented content. PT is a stakeholder and board member of POLTREG venture. Medical University of Gda\u0144sk received payment for the license to the presented content.\u00a0AJ, AJC, AK, BK, DIG, ES, JK, JS, KK, MG, MGrz, MK, MZ, PG, P\u0141, and WN have no conflicts of interest relevant to the contents of this article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was conducted according to the Declaration of Helsinki principles. The protocol has been registered in the EudraCT database under the number 2014-004320-22 and received approval from the Institutional Review Board of the Medical University of Gda\u0144sk (no. NKBBN\/414\/2012 and NKBBN\/414-163\/2017).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Written informed consent was received from all the participants at recruitment, before any medical procedure was commenced.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All the patients signed written consent that the data obtained in the study could be used for scientific publications, provided the data are anonymized.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The datasets used and\/or analyzed during the current study are available from the corresponding author on reasonable request.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of data and material"}},{"value":"Not applicable.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}},{"value":"KC was the principal investigator and contributed to the study design, protocol writing, data collection, analysis, interpretation, and writing and reviewing the report. DIG was a head of the R&D team and contributed to the study design, cell preparation, data collection, analysis, and writing and reviewing the report. AJ contributed to the study design, protocol writing, MRI data collection, analysis, interpretation, and writing and reviewing the report. MZ contributed to lab assays, data collection, and interpretation. P\u0141 contributed to patient care, data collection, and interpretation. MG contributed to the cell preparation, data collection, analysis, and reviewing the report. MGrz contributed to MRI data collection, analysis, and interpretation. KK contributed to patient care, data collection, and interpretation. AK contributed to MRI data collection, analysis, and interpretation. PG contributed to patient care, data collection, and interpretation. AJC contributed to clinical assessment, and data collection. JS\u00a0and JK contributed to the cell preparation, data collection, and analysis. MK contributed to patient care, data collection, and interpretation. BK, WN, and ES contributed to study design, data collection, and interpretation and reviewed the report. PT is the guarantor of the study, and supervised the whole process and contributed to the study design, protocol writing, cell preparation, data collection, analysis, interpretation, and writing and reviewing the report.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author contributions"}}]}}