Treatment of progressive multiple sclerosis with high-dose all-trans retinoic acid – no clear evidence of positive disease modifying effects

Author:

Ruschil ChristophORCID,Dubois Evelyn,Stefanou Maria-Ioanna,Kowarik Markus Christian,Ziemann Ulf,Schittenhelm Marcus,Krumbholz Markus,Bischof Felix

Abstract

Abstract Background All-trans retinoic acid (ATRA) is an acid derivative of vitamin A which is discussed as a promising candidate to ameliorate the disease course of multiple sclerosis (MS) by immunomodulation or even by promoting regeneration in progressive MS. Here we report a patient who significantly improved for MS related disability following administration of chemotherapy including ATRA for mitoxantrone-related acute promyelocytic leukemia and assess the effect of high-dose ATRA in three additional patients with progressive MS. Methods Patients with progressive MS who had failed previous therapies were treated with high-dose ATRA. Patients underwent clinical and routine laboratory monitoring. Additionally, PBMCs were analyzed by flow cytometry for lymphocyte subsets. Results ATRA was well tolerated and no pathological laboratory abnormalities were observed. After initial mild (not statistically significant) improvement of EDSS and mean MSFC z-score, ongoing disease progression was observed. One patient subacutely experienced severe cognitive and motor worsening. Cerebral MRI revealed persistent gadolinium-enhancing lesions. Flow cytometric alterations of peripheral blood naïve, central memory and effector memory CD4 and CD8 T cells, B lymphocytes, plasma cells, memory B cells, plasmablasts and natural killer (NK) cells did not reach statistical significance. Conclusions Stand-alone therapy with ATRA did not ameliorate progressive MS in our limited cohort and we did not observe consistent alterations of T and B cell subsets. Intriguingly, application of ATRA may have caused marked disease exacerbation in one patient.

Publisher

Springer Science and Business Media LLC

Subject

Automotive Engineering

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