Centre National De La Recherche Scientifique

Institut National De La Sante Et De La Recherche Medicale

UniversitÉ Paris Descartes

Fondation Imagine

Assistance Publique - Hopitaux De Paris (aphp)

Assistance Publique-hopitaux De Paris

Université De Caen Normandie

Centre Hospitalier Regional Universitaire De Caen

Universite Paris Cité

Inserm

Flavia Guillem

Olivier Hermine

Jean-Benoit Arlet

Michaela Fontenay

Genevieve Courtois

Sophia Ladraa

Gandhi Damaj

Genevève Courtois

Geneviève Courtois

Jean-Benoît Arlet

The present invention relates to methods and pharmaceutical compositions for the treatment of systemic mastocytosis. The inventors showed the effect of KPT-251 treatment on SCF-dependent human Mast cell (MC) line without KIT mutation (WT ROSA) and on two factor-independent MC lines with KIT mutations : ROSA &#x394; 417-419 insY and ROSA D816V. KPT is a Selective Inhibitor of Nuclear Export (SINE) that specifically inhibits the activity of the exportin-1 (XPO1). KPT-251 treatment induces minimal toxicity in non-cancerous hematopoietic cells both in vitro and in vivo. In particular, the present invention relates a method of treating systemic mastocytosis in patient in need thereof comprising administering to the patient a therapeutically effective amount of a XPO1 inhibitor.

Methods and pharmaceutical compositions for the treatment of systemic mastocytosis

The present invention relates to methods and pharmaceutical compositions for the treatment of beta-thalassemias. In particular, the present invention relates to an XPO1 inhibitor for use in a method for treating beta-thalassemia in a subject in need thereof.

Methods and pharmaceutical compositions for the treatment of beta-thalassemias

The present invention provides methods and pharmaceutical compositions designed to intervene in this defective process and to promote or restore erythrocyte maturation in individuals suffering from a myelodysplastic syndrome. The methods involve maintaining the activity of GATA-1 by preventing sequestration of Hsp70 in the cytoplasm. Accordingly, it is an object of this invention to provide methods of restoring or increasing erythrocyte maturation in a subject suffering from a myelodysplastic syndrome by preventing proteolytic inactivation of GATA-1. In some embodiments, preventing is achieved by administering to the subject a compound that inhibits the XPO1 nuclear transporter.

Methods and pharmaceutical compositions for the treatment of myelodysplastic syndromes

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Paris, France

Flavia Guillem