Pixantrone (BBR2778) reduces the severity of experimental autoimmune myasthenia gravis in Lewis rats

Federica Ubiali, Sara Nava, Valeria Nessi, Renato Longhi, Gabriella Pezzoni, Raffaella Capobianco, Renato Mantegazza, Carlo Antozzi, Fulvio Baggi

Research output: Contribution to journalArticlepeer-review

Abstract

Pixantrone (BBR2778) (PIX) and mitoxantrone share the same mechanism of action because both drugs act as DNA intercalants and inhibitors of topoisomerase II. PIX is an interesting candidate immunosuppressant for the treatment of autoimmune diseases because of its reduced cardiotoxicity compared with mitoxantrone. The clinical response to conventional immunosuppressive treatments is poor in some patients affected by myasthenia gravis (MG), and new but well-tolerated drugs are needed for treatmentresistant MG. PIX was tested in vitro on rat T cell lines specific for the immunodominant peptide 97-116 derived from rat acetylcholine receptor (AChR), and showed strong antiproliferative activity in the nanomolar range. We demonstrate in this study that PIX administration reduced the severity of experimental autoimmuneMGin Lewis rats. Biological and immunological analysis confirmed the effect of PIX, compared with vehicle-treated as well as mitoxantrone-treated experimental autoimmune MG rats. Anti-rat AChR Abs were significantly reduced in PIX-treated rats, and AChR content in muscles were found increased. Torpedo AChR-induced T cell proliferation tests were found reduced in both in vitro and ex vivo experiments. The effectiveness and the reduced cardiotoxicity make PIX a promising immunosuppressant agent suitable for clinical investigation in MG, although additional experiments are needed to confirm its safety profile in prolonged treatments.

Original languageEnglish
Pages (from-to)2696-2703
Number of pages8
JournalJournal of Immunology
Volume180
Issue number4
Publication statusPublished - Feb 15 2008

ASJC Scopus subject areas

  • Immunology

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