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Differential targeting of immune-cells by Pixantrone in experimental myasthenia gravis
Roberta Marolda1, Chiara Ruocco, Chiara Cordiglieri
1Preclinical Neuroimmunology Laboratory, Neurology IV, Neurological Institute Carlo Besta, Milan, Italy.
Abstract:
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-8.12 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.
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