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Article History

Received: 16 February 2021

Accepted: 23 March 2021

First Online: 10 May 2021

Declarations

:

: All patients consented to off-label treatment with ATRA after previous treatment had failed and provided written informed consent for the provision of blood samples for research purposes. The protocol for processing and analyzing peripheral blood samples was approved by the Ethics Committee of the University of Tübingen, Germany (029/2014BO2). Ethics approval of individualized treatment with ATRA with a defined protocol (including ≤4 patients treated) was not necessary under German ethics legislation (“Individueller Heilversuch”). For control purpose, we used an internal cohort of progressive MS patients (<i>n</i> = 52) who presented in our outpatient clinic between 2014 and 2019 (ethics approval for retrospective analysis 329/2019B01 by Ethics Committee of the University of Tübingen).

: All patients provided written consent for publication.

: Christoph Ruschil is supported by fortüne/PATE (grant no 2536-0-0) from the medical faculty, Eberhard-Karls University of Tübingen; not related to this project. Evelyn Dubois reports no disclosures. Maria-Ioanna Stefanou reports no disclosures. Ulf Ziemann has received grants from European Research Council (ERC), German Research Foundation (DFG), German Federal Ministry of Education and Research (BMBF), Bristol Myers Squibb, Janssen Pharmaceutica NV, Servier, Biogen Idec GmbH, and personal fees from Bayer Vital GmbH, Pfizer GmbH, CorTec GmbH, all not related to this work. Markus C Kowarik receives financial support from Merck, Sanofi-Genzyme, Novartis, Biogen, Celgene and Roche, not related to this project. Marcus Schittenhelm receives financial support from Pfizer and Astellas, not related to this project. M S was supported by the IZKF Program of the medical faculty, Eberhard-Karls University of Tübingen. M. Krumbholz received travel funding and speaker honoraria from Merck, Novartis and Roche, and research support from Merck. F. Bischof served on the scientific advisory board for Genzyme, Novartis, and Roche, received speaker honoraria and travel funding from Biogen Idec, Genzyme, and Novartis, and received research support from Novartis, all unrelated to this work.