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Treatment of progressive multiple sclerosis with high-dose all-trans retinoic acid - no clear evidence of positive disease modifying effects.
Ruschil, Christoph; Dubois, Evelyn; Stefanou, Maria-Ioanna; Kowarik, Markus Christian; Ziemann, Ulf; Schittenhelm, Marcus; Krumbholz, Markus; Bischof, Felix.
Afiliação
  • Ruschil C; Department of Neurology & Stroke, Eberhard-Karls University, Tübingen, Germany. Christoph.ruschil@uni-tuebingen.de.
  • Dubois E; Hertie Institute for Clinical Brain Research, Eberhard-Karls University, Tübingen, Germany. Christoph.ruschil@uni-tuebingen.de.
  • Stefanou MI; Department of Neurology & Stroke, Eberhard-Karls University, Tübingen, Germany.
  • Kowarik MC; Hertie Institute for Clinical Brain Research, Eberhard-Karls University, Tübingen, Germany.
  • Ziemann U; Department of Neurology & Stroke, Eberhard-Karls University, Tübingen, Germany.
  • Schittenhelm M; Hertie Institute for Clinical Brain Research, Eberhard-Karls University, Tübingen, Germany.
  • Krumbholz M; Department of Neurology & Stroke, Eberhard-Karls University, Tübingen, Germany.
  • Bischof F; Hertie Institute for Clinical Brain Research, Eberhard-Karls University, Tübingen, Germany.
Neurol Res Pract ; 3(1): 25, 2021 May 10.
Article em En | MEDLINE | ID: mdl-33966627
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Neurol Res Pract Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Alemanha País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Neurol Res Pract Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Alemanha País de publicação: Reino Unido