Inotropic antibodies and therapeutic uses thereof

摘要

Antibodies binding to sites on the alpha-subunit of the (Na++K+)-ATPase increase cardiac contraction of both ventricular myocytes and mouse heart. In particular, antibodies binding to the RSATEEEPPNDD (SEQ ID NO: 1) or DVEDSYGQQWTYEQR (SEQ ID NO: 2) peptides (or isoforms/derivatives thereof) of the alpha-subunit of the (Na++K+)-ATPase, have been found to be highly inotropic. Both the antibodies and the peptides are important for the treatment of human heart failure and other contractile disorders.

主权项

1. A method of producing a positive inotropic effect in a mammalian host comprising administering to said mammalian host a therapeutically effective amount of an antibody which binds to a peptide consisting of the amino acid sequence as set forth in RSATEEEPPNDD (SEQ ID NO:1), wherein said antibody binds (Na++K+)-ATPase to increase intracellular calcium, wherein the antibody enhances the velocity of shortening of the ventricular myocyte and increases the force of contraction of the heart cells.