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

- We evaluated Pixantrone as immunosuppressant treatment in EAMG.
- Immunosuppressive activity of PIX can be efficiently evaluated in the sera.
- Only actively proliferating CD4+ Teff cells are inhibited by Pixantrone at low IC50.
- Dendritic cells and B cells are not affected by Tcell-suppressive doses of PIX.
- Pixantrone potential as therapeutic drug should be assessed in MG clinical trials.

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.