公开(公告)号：WO2021245224A1

公开(公告)日：2021-12-09

申请号：PCT/EP2021/064988

申请日：2021-06-04

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITÉ DE PARIS ,  FONDATION IMAGINE ,  ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP)

发明人： ROZET, Jean-Michel ,  FARES TAIE, Lucas ,  NEDELEC, Brigitte ,  ANGEE, Clémentine ,  KAPLAN, Josseline

IPC分类号： A61K48/00 ,  C12N15/86 ,  A61P27/02 ,  C12N15/113 ,  C12N2310/20 ,  C12N2750/14143

摘要： The present invention relates to a method for treating ocular disease in a subject in need thereof comprising a step of administering to said subject a therapeutically amount of an inhibitor of SOX21 gene expression and/or activity. By studying a mouse model of congenital microcoria, the inventors demonstrate that this ultra-rare and purely ocular disease is due to unanticipated complex mechanisms linked with 3D regulation of gene expression. They propose that the disease is due to the illegitimate expression of a transcription factor, SOX21, induced by the adoption of a DCT enhancer(s). They show that SOX21 binds to a regulatory region of the Tgfß2 gene and the inventors demonstrate overexpression of this trophic factor in the iris and accumulation of its product in the aqueous humor of the mouse carrying the minimal MCOR deletion which recapitulates the observed accumulation in patients with POAG and one of our patient with MCOR.

公开(公告)号：WO2021156369A1

公开(公告)日：2021-08-12

申请号：PCT/EP2021/052668

申请日：2021-02-04

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP) ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  FONDATION IMAGINE ,  UNIVERSITÉ DE PARIS

发明人： DE LONLAY-DEBENEY, Pascale ,  VAN ENDERT, Peter ,  MONTEALEGRE, Sebastian ,  TUCHMANN-DURAND, Caroline ,  CACCAVELLI, Laure ,  MADRANGE, Marine ,  RENARD, Perrine

IPC分类号： A61K31/4706 ,  A61P21/00

摘要： Lipin-1 deficiency is a rare, life-threatening condition that causes severe rhabdomyolysis episodes (RM) triggered by febrile illness and effort. Now, the inventors treated 10 patients with LPIN1 mutations with hydroxychloroquine (HCQ) in an off open-label use phases 1 and 2 study, to assess safety, clinical, and biological effects of the drug. A first inclusion group of patients were treated with oral HCQ at a dose of 6.5 mg/Kg/day in one intake, not exceeding 400 mg/day. Five patients have not presented any new acute RM under treatment, except for 2 patients experimented one and two episodes of RM respectively despite HCQ in a context of gastroenteritis. Plasma levels of HCQ were in the range of 400 ng/ml except in the two patients who experimented RM, in whom the plasma HCQ levels were higher (1000 ng/ml). With a therapeutic adjustment, in order to maintain plasma levels of HCQ under 700 ng/ml, in a new group of patients, two patients did not suffer from new acute RM under treatment. HCQ had not seem to have benefit effect for one patient.Thus, the inventors describe the first human experience with HCQ for Lipin-1 disease. The results allow the inventors to propose low doses of HCQ as a long-term treatment to prevent further relapses in this severe disease.

公开(公告)号：WO2021009336A1

公开(公告)日：2021-01-21

申请号：PCT/EP2020/070244

申请日：2020-07-17

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  FONDATION IMAGINE ,  ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP) ,  UNIVERSITÉ DE PARIS ,  UNIVERSITÉ TOULOUSE III – PAUL SABATIER

发明人： LAGRESLE-PEYROU, Chantal ,  OLICHON, Aurélien ,  SADEK-ROCK, Hanem ,  ANDRE, Isabelle ,  CAVAZZANA, Marina

IPC分类号： A61K38/17 ,  A61K31/713 ,  A61P35/02 ,  C07K14/00 ,  A61K48/00

摘要： The inventors have identified an autosomal dominant (AD) missense mutation in the RAC2 gene (coding for Ras-related C3 botulinum toxin substrate 2 (RAC2)) in three Severe combined immunodeficiencies (SCID) patients whose clinical presentation overlaps with the RD SCID form but who lack AK2 mutations and deafness. Using biochemical and in vitro differentiation assays, the inventors demonstrated that the RAC2 mutation was closely related to an impairment in cell differentiation capacity and defects in cellular and mitochondrial networks. Taken as a whole, the data demonstrate that a dominant gain-of-function (GOF) mutation in the RAC2 protein's GDP/GTP binding site inhibits HSPC differentiation and leads to a severe AD form of SCID with a clinical presentation of RD. Accordingly, the results prompt to consider that introduction of the identified RAC2 mutein in the hematopoietic lineage would be suitable for inducing full ablation of hematopoiesis.

公开(公告)号：WO2020245210A1

公开(公告)日：2020-12-10

申请号：PCT/EP2020/065369

申请日：2020-06-03

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITÉ DE PARIS ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP) ,  FONDATION IMAGINE ,  CONSERVATOIRE NATIONAL DES ARTS ET MÉTIERS (CNAM) ,  PSB PARIS SCHOOL OF BUSINESS

发明人： LEPELLETIER, Yves ,  MONTES, Matthieu ,  DEMANGE, Luc ,  RAYNAUD, Françoise ,  RIGNAULT-BRICARD, Rachel ,  HERMINE, Olivier ,  LOPEZ, Nicolas

IPC分类号： A61K31/4184 ,  A61K31/437 ,  A61P35/00 ,  A61K45/06

摘要： Neuropilin-1 is henceforth a relevant target in cancer treatment, however way-of-action is remains partly elusive and the development of small inhibitory molecules is therefore required for its study. Here, the inventors report that two neuropilin small-sized antagonists (NRPa-47, NRPa-48), VEGF-A165/NRP-1 binding inhibitors, are able to decrease VEGF-Rs phosphorylation and to modulate their downstream cascades in triple negative breast cancer cell line (MDA-MB-231). In particular, the inventors showed for the first time, how NRPa may altered tumor cell signaling and contributed in the down-modulation of the cancer therapeutic key factor p38α-kinase phosphorylation. More importantly, the association of NRPa with a p38α inhibitor leads to additional and/or synergistic effect of these drugs (depending of the dose used) for significantly reducing breast cancer cell proliferation Thus, the efficient association of NRPa and p38α-kinase inhibitors are thus credible for the treatment of cancer.

公开(公告)号：WO2020212395A1

公开(公告)日：2020-10-22

申请号：PCT/EP2020/060543

申请日：2020-04-15

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  FONDATION IMAGINE ,  UNIVERSITÉ DE PARIS ,  ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP)

发明人： BODEMER, Christine ,  DELMAS, Patrick ,  GRECO, Céline

IPC分类号： A61K31/407 ,  A61K31/506 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/553 ,  A61P29/02

摘要： An increasing body of evidence suggests that Nav1.7 encoded by SCN9A gene may play a key role in various pain states, including acute, inflammatory and/or neuropathic pain. The inventors now report an efficient treatment for severe cases of primary erythromelagia linked to a specific SCN9A mutation. In particular the inventors demonstrated that the inhibition of JAK2 produces a rightward shift in the voltage dependent activation of mutant Nav1.7 channels, thereby normalizing the function of mutant Nav1.7 channels. On this basis, the inventors treated a patient suffering from PE with very severe refractory pain with a JAK2 inhibitor (ruxolitinib) and showed the therapy leads to considerable reduction of pain. Accordingly, the present invention relates to the use of JAK inhibitors for the treatment of painful conditions involving Nav1.7 channels.

公开(公告)号：WO2020079162A1

公开(公告)日：2020-04-23

申请号：PCT/EP2019/078241

申请日：2019-10-17

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  FONDATION IMAGINE ,  UNIVERSITÉ PARIS DESCARTES ,  ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP)

发明人： CAVAZZANA, Marina ,  ANDRE, Isabelle ,  LAGRESLE-PEYROU, Chantal ,  SADEK-ROCK, Hanem

IPC分类号： A61K31/713 ,  C12N15/113 ,  A61P35/02

摘要： Conditioning regimens aiming at preparing a subject to hematopoietic stem cell transplantation are associated with immediate and delayed toxicities. Accordingly, there is a need for new method that will allow full ablation of hematopoiesis. The inventors identify such a novel target. Indeed, the inventors get interested in three patients presenting a severe SCID form at birth associated with septicaemia. Genetic studies of patients' fibroblasts lead them to identify the same mutation in the Ras-related C3 botulinum toxin substrate 2 (RAC2) gene. More particularly, they showed that introduction of the mutation in hematopoietic stem and progenitor cell (HSPC) leads to a drastic decrease of the proliferation and differentiation toward different lineages (T cells, granulocytes, and monocytes). These results thus suggest that inhibition of RAC2 would be suitable for inducing ablation of hematopoiesis.

公开(公告)号：WO2018178007A1

公开(公告)日：2018-10-04

申请号：PCT/EP2018/057634

申请日：2018-03-26

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  FONDATION IMAGINE ,  UNIVERSITÉ PARIS DESCARTES ,  ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP)

发明人： LATOUR, Sylvain ,  FISCHER, Alain ,  WINTER, Sarah

IPC分类号： A61K31/00 ,  A61P37/00 ,  A61K35/02

摘要： The inventors report two siblings presenting recurrent EBV infection and Hodgkin lymphoma caused by a homozygous loss-of-function mutation in RASGRPl, a T-cell specific nucleotide exchange factor (GEF) known to activate the RAS-induced MAPK/ERK kinases pathway. In response to TCR stimulation, RASGRP 1 -deficient T cells exhibited defective ERK kinases activation and impaired proliferation that was restored by expression of wild-type RASGRPl. Thus, these results identify a novel primary immunodeficiency that highlights T- cell proliferation and offers the opportunity to develop RASGRPl inhibitor for inhibiting T cell proliferation in a subject in need thereof.

公开(公告)号：WO2016142385A1

公开(公告)日：2016-09-15

申请号：PCT/EP2016/054927

申请日：2016-03-08

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  ASSISTANCE PUBLIQUE HOPITAUX DE PARIS ,  UNIVERSITE PARIS DESCARTES ,  FONDATION IMAGINE

发明人： ROZET, Jean-Michel ,  FARES TAIE, Lucas ,  KAPLAN, Josseline ,  ROCHE, Olivier

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6883 ,  C12Q2600/156

摘要： The present invention relates to a method for diagnosing ocular anterior chamber dysgenesis.

摘要翻译： 本发明涉及一种诊断眼前房发育不良的方法。

公开(公告)号：WO2015193480A1

公开(公告)日：2015-12-23

申请号：PCT/EP2015/063829

申请日：2015-06-19

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  UNIVERSITÉ PARIS DESCARTES ,  FONDATION IMAGINE ,  UNIVERSITÉ PARIS DIDEROT - PARIS 7 ,  UNIVERSITÉ PARIS-SUD ,  ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP)

发明人： CRUZ-MOURA, Ivan ,  HERMINE, Olivier ,  PAUBELLE, Etienne ,  DUSSIOT, Michaël ,  TROVATI MACIEL, Thiago ,  ZYLBERSZTEJN, Florence

IPC分类号： A61K31/593 ,  A61K31/341 ,  A61K31/53

CPC分类号： A61K31/706 ,  A61K31/341 ,  A61K31/53 ,  A61K31/593 ,  A61K45/06 ,  A61K2300/00

摘要： The present invention concerns a combination of (i) a DNA methylation inhibitor, and (ii) a Vitamin D receptor agonist, for simultaneous or sequential use in the treatment of a drug resistant cancer and/or in prevention of tumor relapse in a patient suffering from cancer. The present invention also relates to a combination of (i) a DNA methylation inhibitor, and (ii) a Vitamin D receptor agonist, for increasing, restoring or enhancing sensitivity of a patient suffering from cancer to a chemotherapeutic drug in a patient suffering from cancer.

摘要翻译： 本发明涉及（i）DNA甲基化抑制剂和（ii）维生素D受体激动剂的组合，用于同时或顺序用于治疗耐药性癌症和/或预防患者的肿瘤复发 从癌症。 本发明还涉及（i）DNA甲基化抑制剂和（ii）维生素D受体激动剂的组合，用于在患有癌症的患者中增加，恢复或增强患有癌症的患者对化学治疗药物的敏感性 。

公开(公告)号：WO2015189186A1

公开(公告)日：2015-12-17

申请号：PCT/EP2015/062807

申请日：2015-06-09

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  FONDATION IMAGINE ,  ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP) ,  UNIVERSITÉ PARIS DESCARTES ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS)

发明人： HERMINE, Olivier

IPC分类号： A61K31/165 ,  A61P35/02

CPC分类号： A61K31/422 ,  A61K31/00 ,  A61K31/366

摘要： 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 syndromeby 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.

摘要翻译： 本发明提供了设计用于干预该缺陷过程并促进或恢复患有骨髓增生异常综合征的个体的红细胞成熟的方法和药物组合物。 该方法涉及通过防止细胞质中Hsp70的螯合来维持GATA-1的活性。 因此，本发明的目的是提供通过预防GATA-1的蛋白水解失活来恢复或增加患有骨髓增生异常综合征的受试者的红细胞成熟的方法。 在一些实施方案中，通过向受试者施用抑制XPO1核转运蛋白的化合物来实现预防。