A - Human Necessities – 61 – K
Patent
A - Human Necessities
61
K
A61K 39/395 (2006.01) C12N 5/07 (2010.01) C12N 5/077 (2010.01) C12N 5/078 (2010.01) A61K 31/16 (2006.01) A61K 31/415 (2006.01) A61K 31/4164 (2006.01) A61K 31/7088 (2006.01)
Patent
CA 2742610
Compositions and methods are provided for modulating cell-cell fusion by using agents that modulate expression, activity, or function of intermediate- conductance calcium-activated potassium (SK4) channel. In some embodiments, the compositions and methods of the invention provide for inhibition of multi-nucleated osteoclastogenesis and cell-cell fusion, especially cell fusion involving macrophages. In such embodiments, the compositions can comprise inhibitory nucleic acids, monoclonal antibodies or small molecule inhibitors of the SK4 channels and find use in preventing and/or treating various diseases or disorders including bone loss, autoimmune and inflammatory diseases or disorders, implant and transplant rejection, and cancer metastasis. In other embodiments, the compositions and methods of the invention provide for activation of cell-cell fusion. Also provided are methods to screen for SK4 channel modulators (inhibitors or activators) that modulate cell-cell fusion, particularly macrophage cell fusion.
L'invention concerne des compositions et des procédés pour moduler une fusion cellule-cellule par le biais d'agents qui modulent l'expression, l'activité ou la fonction de canaux potassiques activés par le calcium (SK4) de conductance intermédiaire. Selon certaines variantes, les compositions et les procédés permettent d'inhiber l'ostéoclastogenèse multinucléée et la fusion cellule-cellule, en particulier la fusion cellulaire qui fait intervenir des macrophages. Selon ces variantes, les compositions peuvent comprendre des acides nucléiques inhibiteurs, des anticorps monoclonaux ou des inhibiteurs de molécules de petite taille des canaux SK4 et trouver une utilisation dans la prévention et/ou le traitement de divers maladies ou troubles, y compris la perte osseuse, les maladies ou affections autoimmunes et inflammatoires, le rejet d'implants et de greffons, et la métastase cancéreuse. Selon d'autres variantes, les compositions et les procédés permettent d'activer la fusion cellule-cellule On décrit aussi des procédés permettant de cribler les modulateurs (inhibiteurs ou activateurs) qui modulent la fusion cellule-cellule, en particulier la fusion cellulaire faisant intervenir des macrophages.
Li Jun
Vignery Agnes
Boehringer Ingelheim International Gmbh
Fetherstonhaugh & Co.
Yale University
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