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    TREM-1 INHIBITORS FOR THE TREATMENT OF VASO-OCCLUSIONS AND TISSUE INJURIES IN PATIENTS SUFFERING FROM SICKLE CELL DISEASE
    5.
    发明申请
    TREM-1 INHIBITORS FOR THE TREATMENT OF VASO-OCCLUSIONS AND TISSUE INJURIES IN PATIENTS SUFFERING FROM SICKLE CELL DISEASE 有权

    公开(公告)号：US20230016187A1

    公开(公告)日：2023-01-19

    申请号：US17778571

    申请日：2020-11-24

    申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITÉ PARIS CITÉ ,  INOTREM

    发明人： Pierre-Louis THARAUX ,  Olivia LENOIR ,  Thomas MINTZ

    IPC分类号： A61K38/04 ,  A61P7/00

    摘要： Sickle cell disease (SCD) is a single gene disorder characterized by mutant hemoglobin-S(HbS) and chronic intravascular haemolysis. Painful vaso-occlusive crises (VOC) are typical of SCD and often associated to a further rise in hemolysis. VOC is the clinically painful form of vaso-occlusion, that is due to the aggregation of red blood cells in the capillaries and venules. Such event is promoted or aggravated by adhesion of polymorphonuclear neutrophils (PMNs) to red blood cells and the endothelium leading to tissue ischemia, inflammation and imperfect repair. Repeated vaso-occlusion and PMNs interactions with the vascular endothelium are thought to promote microvascular injuries in SCD patients. The inventors tested the effect of pharmacological inhibition of TREM-1 with LR12 peptide in two experimental vaso-occlusive crisis models. Additional validation of TREM-1 involvement in vaso-occlusion was verified using mice with sickle cell disease and Trem-1 gene deficiency. In particular, the inventors showed that TREM-1 inhibition is particular suitable for limiting the severity of vaso-occlusions. The results obtained by the inventors also suggest that plasmatic concentration of sTREM-1 could be a reliable biomarker for predicting vaso-occlusions and/or SCD-associated organ dysfunction and end-organ damage.

    USE OF SOLUBLE TREM-1 LEVELS FOR IDENTIFYING SUBJECTS SUSCEPTIBLE TO RESPOND TO AN ANTI-INFLAMMATORY THERAPY
    6.
    发明申请
    USE OF SOLUBLE TREM-1 LEVELS FOR IDENTIFYING SUBJECTS SUSCEPTIBLE TO RESPOND TO AN ANTI-INFLAMMATORY THERAPY 有权

    公开(公告)号：US20210364532A1

    公开(公告)日：2021-11-25

    申请号：US17280358

    申请日：2019-09-27

    申请人： INOTREM

    发明人： Marc DERIVE ,  Aurelie OLIVIER ,  Kevin CARRASCO ,  Martin KOCH ,  Margarita SALCEDO-MAGGUILLI ,  Amir BOUFENZER ,  Lucie JOLLY ,  Jean-Jacques GARAUD

    IPC分类号： G01N33/68 ,  A61K38/10

    摘要： A method for identifying human subjects suffering from an inflammatory disorder susceptible to respond to a therapy, in particular to a TREM-1 inhibitor. In particular, an in vitro method for identifying a human subject suffering from an inflammatory disorder, preferably an acute inflammatory disorder such as SIRS, sepsis or septic shock, susceptible to respond to a therapy, in particular to a TREM-1 inhibitor. The method includes the steps of a) measuring the level of soluble triggering receptors expressed on myeloid cells-1 (sTREM-1) in a biological sample from the human subject, comparing the level of sTREM-1 measured at step a) to a predetermined sTREM-1 value, and c) identifying a human subject suffering from an inflammatory disorder with a level of sTREM-1 measured at step a) higher than the predetermined sTREM-1 value of step b) as susceptible to respond to a therapy, in particular to a TREM-1 inhibitor.