Abstract: FGFR3-related chondrodysplasias represent a group of rare diseases. Among them, achondroplasia, a nonlethal form of chondrodysplasia, is the most common type of dwarfism. The mutation, which produce an increase of FGFR3 function, affects many tissues, most strikingly the cartilaginous growth plate and bone in the growing skeleton, leading to a variety of manifestations and complications. In attempt to find a new therapeutic approach for FGFR3-related chondrodysplasia, the inventors purified (?)-epicatechin from T. cacao and showed that (?)-epicatechin treatment significantly increases the length of the Fgfr3Y367C/+ femurs comparing to Fgfr3+/+ femurs and improves the whole growth plate cartilage. The present invention thus relates to the use of (?)-epicatechin for the treatment of FGFR3-related chondrodysplasias.

Abstract: Friedreich ataxia (FRDA) is caused by a GAA repeat expansion in FXN gene that encodes a mitochondrial protein, frataxin, involved in iron sulfur complex (ISC) assembly. Frataxin deficiency results in abnormal ISC containing proteins, namely respiratory chain complex I-III and aconitases and accumulation of iron in brain and heart of patients. Here, the inventors show that FRDA fibroblasts are unable to limit iron uptake inducing a massive cytosolic iron accumulation and to a lesser extent in mitochondria. The inventors also observed increased transferrin receptor (TfR1) steady state levels and membrane TfR1 accumulation that they ascribed to impaired post-translational modification by palmitoylation as well as delayed transferrin recycling. Finally, the inventors showed that artesunate, dichloroacetate and Coenzyme-A improved TfR1 palmitoylation and thus represent candidate molecules for the treatment of patients with Friedreich ataxia.

Abstract: The invention relates to an in vitro method to generate T cell progenitors, comprising the step of culturing CD34+ cells in a medium containing TNF-alpha and/or an antagonist of the Aryl hydrocarbon/Dioxin receptor, in particular StemRegenin 1 (SR1), in presence of a Notch ligand and optionally a fibronectin fragment.

Abstract: The present invention relates to an in vitro method of culturing a segmented filamentous bacterium strain, comprising co-culturing said segmented filamentous bacterium strain with a eukaryotic host cell, wherein the culture is performed at an O2 level inferior to 5% in a rich tissue culture liquid medium containing bacterial medium components including iron. The present invention also relates to methods for genetically modifying a segmented filamentous bacterium strain comprising a step a culturing the strain in vitro.

Abstract: The present invention relates to methods for performing antisense oligonucleotide-mediated exon skipping in the retina of a subject in need thereof. In particular, the present invention relates to a method for performing antisense oligonucleotide-mediated exon skipping in a retina cell of a subject comprising the step of injecting into the vitreous of the subject an amount of the antisense oligonucleotide.

Abstract: A topical composition including erlotinib and a pharmaceutically acceptable excipient for use in the treatment of a keratoderma in a child, preferably a palmoplantar keratoderma (PPK), wherein the composition is topically administered. The composition may further include a penetration enhancer. The treated subject may be younger than three years old. Also, woven or non-woven fabric support including erlotinib and to dressings, patches, gloves and socks having the support useful in the treatment of a PPK.

Abstract: The present invention relates to methods and pharmaceutical compositions for the treatment of diseases mediated by the NRP-1/OBR complex signaling pathway. In particular, the present invention relates to a method for treating a disease selected from the group consisting of cancers, obesity and obesity related diseases, anorexia, autoimmune diseases and infectious diseases in a subject in need thereof comprising administering the subject with a therapeutically effective amount of an antagonist of the NRP-1/OBR signaling pathway.

Abstract: The inventors demonstrate for the first time the activation of the Hedgehog (HH) signaling pathway in normal and abnormal human mast cells (MCs). These results prompt the inventors to explore the consequence of the inhibition of the HH pathway, especially the canonical pathway, on MC proliferation. They demonstrate that Hedgehog inhibitors inhibit proliferation and induces apoptosis of mast cells. Accordingly the present invention relates to a method of treating a mast cell disease in a patient in need there of comprising administering to the patient a therapeutically effective amount of a Hedgehog inhibitor.

Abstract: 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 ? 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.

Abstract: The invention relates to an in vitro method to generate T cell progenitors, comprising the step of culturing CD34+ cells in a medium containing TNF-alpha and/or an antagonist of the Aryl hydrocarbon/Dioxin receptor, in particular StemRegenin 1 (SR1), in presence of a Notch ligand and optionally a fibronectin fragment.

Abstract: The invention relates to an in vitro method to generate T cell progenitors, comprising the step of culturing CD34+ cells in a medium containing TNF-alpha and/or an antagonist of the Aryl hydro-carbon/Dioxin receptor, in particular StemRegenin 1 (SR1), in presence of a Notch ligand and optionally a fibronectin fragment.

Abstract: The invention relates to an in vitro method to generate T cell progenitors, comprising the step of culturing CD34+ cells in a medium containing TNF-alpha and/or an antagonist of the Aryl hydro-carbon/Dioxin receptor, in particular StemRegenin 1 (SR1), in presence of a Notch ligand and optionally a fibronectin fragment.

Abstract: The present invention relates to methods and pharmaceutical compositions for treating rhabdomyolysis.

Abstract: The present invention relates to agents capable of inhibiting the binding between Leptin and Neuropilin-1 (NRP1) and uses thereof in the therapeutic field.

Abstract: The invention relates to an in vitro method to generate T cell progenitors, comprising the step of culturing CD34+ cells in a medium containing TNF-alpha and/or an antagonist of the Aryl hydro-carbon/Dioxin receptor, in particular StemRegenin 1 (SR1), in presence of a Notch ligand and optionally a fibronectin fragment.

Abstract: The present invention relates to an in vitro method of culturing a segmented filamentous bacterium strain, comprising co-culturing said segmented filamentous bacterium strain with a eukaryotic host cell, wherein the culture is performed at an O2 level inferior to 5% in a rich tissue culture liquid medium containing bacterial medium components including iron. The present invention also relates to methods for genetically modifying a segmented filamentous bacterium strain comprising a step a culturing the strain in vitro.

Abstract: The invention relates to the field of cell therapy and to an in vitro method for generating T-cell progenitors, comprising the step of exposing CD34+ cells in a medium containing a Notch ligand, a soluble domain of the Delta-like ligand 4, joined to an Fc region of a protein IgG, in the presence of a fragment of fibronectin comprising the motifs RGDS and CS-1 and a heparin-binding domain.

Abstract: 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.

Abstract: 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.

Abstract: Methods and compositions for the treatment of ?-thalassemia are provided. Methods and compositions restore or increase erythrocyte maturation in individuals afflicted with ?-TM by preventing proteolysis of GATA-1 protein. Screening methods for identifying agents which bind heat shock protein 70 (HSP-70) and inhibit HSP-70 ?-globin binding, but which allow GATA-1 protein-HSP-1 binding in a manner that prevents GATA-1 proteolysis.