Differential targeting of immune-cells by Pixantrone in experimental myasthenia gravis

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• 作者：Roberta Marolda^a ; ¹ ; Chiara Ruocco^a ; ¹ ; ² ; Chiara Cordiglieri^a ; Chiara Toscani^a ; Carlo Antozzi^b ; Renato Mantegazza^b ; Fulvio Baggi^a ; ^{baggi@istituto-besta.it}
• 关键词：AChR ; acetylcholine receptor ; TAChR ; Torpedo acetylcholine receptor ; BZ ; Bortezomib ; ¦Á-BTX ; ¦Á-bungarotoxin ; Ct ; cycle threshold ; EAMG ; experimental autoimmune myasthenia gravis ; LNCs ; lymph node cells ; MTX ; mitoxantrone ; MG ; myasthenia gravis ; MMF ; myco
• 刊名：Journal of Neuroimmunology
• 出版年：2013
• 出版时间：15 May, 2013
• 年：2013
• 卷：258
• 期：1-2
• 页码：41-50
• 全文大小：1275 K

文摘

Pixantrone was shown to reduce the severity of clinical manifestation in experimental myasthenia gravis. In the present work we further studied its therapeutic effect. Our results demonstrate that a single administration suppressed AChR-specific immune-responses in primed rats. However, clinical symptoms could be improved only by repeated drug administrations (q7dx6 protocol¡ª8.12 mg/kg); this treatment allowed stable serum drug levels for at least 7 days, as assessed by a functional T-cell bioassay. Pixantrone exerted strong in vitro inhibitory effect only on proliferating T-cells without impairing dendritic cell differentiation and B-cell viability. Our data further demonstrate that Pixantrone is a promising immunosuppressant drug that should be investigated in myasthenia gravis.