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AssigneesYale University, Boehringer Ingelheim International GmbH
InventorsJun Li, Agncs Vignery
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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.
A method for modulating cell fusion of a cell expressing an intermediate-conductance calcium-activated potassium (SK4) channel, the method comprising the step of contacting the cell with an effective amount of an SK4 channel inhibitor or activator, wherein cell fusion is modulated.
A method for modulating osteoclast differentiation and function, the method comprising the step of contacting an osteoclast or an osteoclast precursor with an effective amount of an intermediate-conductance potassium-activated potassium (SK4) channel inhibitor or activator.
A method for preventing or treating bone loss in a subject susceptible to or having bone loss, the method comprising the step of administering to the subject a therapeutically effective amount of an intermediate-conductance calcium-activated potassium (SK4) channel inhibitor to inhibit osteoclast formation, wherein bone loss is prevented or decreased in the subject.
A method for preventing or treating an inflammatory or autoimmune disease characterized by giant cell formation in a subject susceptible to or having the inflammatory or autoimmune disease, the method comprising the step of administering to the subject a therapeutically effective amount of an intermediate-conductance calcium-activated potassium (SK4) channel inhibitor to inhibit giant cell formation, wherein the inflammatory or autoimmune disease is prevented or treated in the subject.
A method for preventing implant or transplant rejection in a subject having an implant or a transplant at a site located within the subject, the method comprising the step of administering to the subject a therapeutically effective amount of an intermediate-conductance calcium-activated potassium (K) channel inhibitor to inhibit giant cell formation at or in the vicinity of the site, wherein rejection of the implant or transplant is prevented in the subject.
A method to prevent cancer metastasis in a subject having cancer, the method comprising the step of administering to the subject a therapeutically effective amount of an intermediate-conductance calcium-activated potassium (SK4) channel inhibitor to inhibit metastatic cancer cell formation, wherein the cancer metastasis is prevented in the subject.
A method to identify an intermediate-conductance calcium-activated potassium (SK4) channel inhibitor that inhibits cell-cell fusion, the method comprising the steps of:
A composition comprising:
Dependencies are inferred from the claim text.