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Cardiac glycosides as treatments for inflammatory and autoimmune diseases



Technology:
Cardiac glycosides inhibit production of interferon-beta

Markets Addressed


Scientists at Harvard University have discovered that cardiac glycosides, a diverse family of sodium pump blockers that are used to treat heart failure and atrial arrhythmia, are also able to inhibit production of interferon-beta. The findings suggest that glycosides could be repurposed to treat inflammatory and autoimmune diseases, including lupus, that are characterized by aberrant production of interferons.

Innovations and Advantages


Bufalin and other cardiac glycoside inhibitors of the sodium-potassium ATPase (sodium pump) potently inhibit the induction of the interferon-beta (IFN-beta) gene by virus, double-stranded RNA or double-stranded DNA. Cardiac glyco¬sides increase the intracellular sodium concentration, which appears to inhibit the ATPase activity of the RNA sensor RIG-I, an essential and early component in the IFN-beta activation pathway. This, in turn, prevents the activation of the critical transcription factors IRF3 and NFkB. Bufalin inhibition can be overcome by expressing a drug-resistant variant of the sodium pump and knocking down the pump by short hairpin RNA inhibits IFNb expression. Thus, bufalin acts exclusively through the sodium pump. We also show that bufalin inhibits tumor necrosis factor (TNF) signaling, at least in part by interfering with the nuclear translocation of NFkB. These findings suggest that bufalin could be used to treat inflammatory and autoimmune diseases in which IFN or TNF are hyperactivated.

Additional Information


Publication:
Ye J, Chen S, Maniatis T. 2011. Cardiac glycosides are potent inhibitors of interferon-beta gene expression. Nat Chem Biol. 7(1):25-33. PubMed PMID: 21076398. doi:10.1038/nchembio.476



Inventor(s):
    Chen, Shuibing
    Maniatis, Thomas
    Ye, Junqiang

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For further information, please contact:
Debra Peattie, Director of Business Development
(617) 495-3067
Reference Harvard Case #3787