Use of a small native peptide activator of SERCA pump for treatment of heart failure and other disorders characterized by cytosolic calcium overload
The present disclosure describes a new native peptide designated herein as Dwarf Open Reading Frame, or DWORF. This peptide enhances the apparent activity of the SERCA pump, is positively inotropic and lusitropic, and therefore is provided as a therapeutic agent for disorders characterized by cytosolic calcium overload.
1. A polynucleotide, comprising a polynucleotide sequence encoding a Dwarf open reading frame (DWORF) consisting of SEQ ID NO: 3, operatively linked to a heterologous cardiac-specific promoter.
2. The polynucleotide of claim 1 , wherein the heterologous cardiac-specific promoter is a cardiomyocyte-specific α-myosin heavy chain (αMHC) promoter.
3. The polynucleotide of claim 1 , wherein the polynucleotide is in a viral expression construct.
4. A vector, comprising a polynucleotide sequence encoding a Dwarf open reading frame (DWORF) consisting of SEQ ID NO: 3, operatively linked to a heterologous cardiac-specific promoter.
5. The vector of claim 4 , wherein the vector is a viral vector.
6. A method of promoting the activity of the SERCA calcium pump in a subject suffering from dilated cardiomyopathy, comprising administering to the subject a viral particle comprising the polynucleotide of claim 1 .
7. The method of claim 6 , wherein the heterologous cardiac-specific promoter is a cardiomyocyte-specific α-myosin heavy chain (αMHC) promoter.