IP Library › Granted Patent US 12,351,609
Granted Patent B2
US 12,351,609 · App. 17/392,137 · Granted Jul 8, 2025

Use of a small native peptide activator of SERCA pump for treatment of heart failure and other disorders characterized by cytosolic calcium overload

Inventors: Eric N. Olson (University Park, TX); Rhonda S. Bassel-Duby (Dallas, TX); Catherine A. Makarewich (Dallas, TX); Benjamin R. Nelson (Dallas, TX)
Assignee: The Board of Regents of The University of Texas System
C07K14/47A61K38/1709A61K45/06A61K48/0058
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Quick Facts
Patent No.
US 12,351,609
App. No.
17/392,137
Granted
Jul 8, 2025
Kind
B2
Abstract

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.

Claims (20)

1. A polynucleotide encoding a human Dwarf open reading frame (DWORF) polypeptide consisting of the sequence of SEQ ID NO: 3, wherein the polynucleotide has at least 80% identity to SEQ ID NO: 4, and is operatively linked to a heterologous muscle-specific or cardiac-specific promoter.

2. The polynucleotide of claim 1 , wherein the polynucleotide has at least 85%, 90% or 95% identity to SEQ ID NO: 4.

3. The polynucleotide of claim 1 , wherein the promoter is a muscle-specific promoter.

4. The polynucleotide of claim 1 , wherein the promoter is a cardiac-specific promoter.

5. The polynucleotide of claim 4 , wherein the cardiac-specific promoter is a cardiomyocyte-specific α-myosin heavy chain (αMHC) promoter.

6. The polynucleotide of claim 1 , wherein the polynucleotide comprises SEQ ID NO: 4.

7. The polynucleotide of claim 1 , wherein the polynucleotide is in a viral expression construct.

8. A vector, comprising a polynucleotide sequence encoding a human Dwarf open reading frame (DWORF) polypeptide consisting of the sequence of SEQ ID NO: 3, wherein the polynucleotide sequence has at least 80% identity to SEQ ID NO: 4, and is operatively linked to a heterologous muscle-specific or cardiac-specific promoter.

9. The vector of claim 8 , wherein the polynucleotide sequence has at least 85%, 90% or 95% identity to SEQ ID NO: 4.

10. The vector of claim 9 , wherein the vector is a viral vector.

11. The vector of claim 8 , wherein the polynucleotide sequence comprises SEQ ID NO: 4.

12. The vector of claim 11 , wherein the vector is a viral vector.

13. The vector of claim 8 , wherein the vector is a viral vector.

14. The vector of claim 8 , wherein the promoter is a muscle-specific promoter.

15. The vector of claim 8 , wherein the promoter is a cardiac-specific promoter.

16. The vector of claim 15 , wherein the cardiac-specific promoter is a cardiomyocyte-specific α-myosin heavy chain (αMHC) promoter.

17. 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 .

18. The method of claim 17 , wherein the polynucleotide has at least 85%, 90% or 95% identity to SEQ ID NO: 4.

19. The method of claim 17 , wherein the polynucleotide comprises SEQ ID NO: 4.

20. The method of claim 17 , wherein the promoter is a cardiomyocyte-specific α-myosin heavy chain (αMHC) promoter.

Continuity (4)
Continuation 16743831 · Jan 15, 2020
Division 15491057 · Apr 19, 2017
Provisional Application 62324706 · Apr 19, 2016
Related Publication 20210380650A1 · Dec 9, 2021
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Cited By (1)
US 12,564,647