IP Library › Granted Patent US 12,295,930
Granted Patent B2
US 12,295,930 · App. 17/268,590 · Granted May 13, 2025

Inducing proliferation of cardiomyocytes and therapeutic uses related thereto

Inventors: Nawazish Naqvi (Lilburn, GA); Ahsan Husain (Atlanta, GA)
Assignee: Emory University
A61K31/198A61K31/138A61K31/403A61K31/713A61K38/179A61K38/1883A61K38/30A61K45/06A61P9/04C12N9/16C12N15/1137C12N2310/14
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Quick Facts
Patent No.
US 12,295,930
App. No.
17/268,590
Granted
May 13, 2025
Kind
B2
Abstract

This disclosure relates to methods of treating or preventing heart malformations or cardiovascular diseases comprising administering an effective amount of thyroid hormone in combination with i) an agent that decreases DUSP5 and/or DUSP6 expression and/or ii) a beta-adrenergic blocking agent to a subject in need thereof. In certain embodiments, this disclosure relates to in vivo and in vitro methods of inducing proliferation of cardiomyocytes using agents or combinations of agents disclosed herein.

Claims (12)

1. A method of treating or preventing a heart malformation or cardiovascular disease comprising administering an effective amount of thyroid hormone in combination with a DUSP5 inhibitor and optionally a beta-adrenergic blocking agent to a subject in need thereof, wherein the DUSP5 inhibitor is an siRNA duplex of GCAUGGCUUACCUUAUGAATT (SEQ ID NO: 111) and UUCAUAAGGUAAGCCAUGCTT (SEQ ID NO: 112).

2. A method of treating or preventing a heart malformation or cardiovascular disease comprising administering an effective amount of thyroid hormone in combination with a DUSP5 inhibitor and optionally a beta-adrenergic blocking agent to a subject in need thereof, wherein the DUSP5 inhibitor is an siRNA duplex of CGUCUAGUUGGGAAAGUAATT (SEQ ID NO: 113) and UUACUUUCCCAACUAGACGTT (SEQ ID NO: 114).

3. A method of treating or preventing a heart malformation or cardiovascular disease comprising administering an effective amount of thyroid hormone in combination with a DUSP5 inhibitor and optionally a beta-adrenergic blocking agent to a subject in need thereof, wherein the DUSP5 inhibitor is an siRNA duplex of GUAGCAAGAUGUUGGCUUUTT (SEQ ID NO: 115), and AAAGCCAACAUCUUGCUACTT (SEQ ID NO: 116).

4. The method of claim 3 , wherein thyroid hormone and the DUSP5 inhibitor is administered in combination with a beta-adrenergic blocking agent selected from acebutolol, atenolol, betaxolol, bisoprolol, carteolol, carvedilol, esmolol, labetalol, metoprolol, nadolol, nebivolol, penbutolol, pindolol, propranolol, sotalol, and timolol, or salts thereof.

5. The method of claim 3 , wherein the DUSP5 inhibitor is administered in combination with a mitogen.

6. The method of claim 5 , wherein the mitogen is neuregulin, IGF-1, YAP1, or ERBB2.

7. The method of claim 1 , wherein thyroid hormone and the DUSP5 inhibitor is administered in combination with a beta-adrenergic blocking agent selected from acebutolol, atenolol, betaxolol, bisoprolol, carteolol, carvedilol, esmolol, labetalol, metoprolol, nadolol, nebivolol, penbutolol, pindolol, propranolol, sotalol, and timolol, or salts thereof.

8. The method of claim 1 , wherein the DUSP5 inhibitor is administered in combination with a mitogen.

9. The method of claim 8 , wherein the mitogen is neuregulin, IGF-1, YAP1, or ERBB2.

10. The method of claim 2 , wherein thyroid hormone and the DUSP5 inhibitor is administered in combination with a beta-adrenergic blocking agent selected from acebutolol, atenolol, betaxolol, bisoprolol, carteolol, carvedilol, esmolol, labetalol, metoprolol, nadolol, nebivolol, penbutolol, pindolol, propranolol, sotalol, and timolol, or salts thereof.

11. The method of claim 2 , wherein the DUSP5 inhibitor is administered in combination with a mitogen.

12. The method of claim 11 , wherein the mitogen is neuregulin, IGF-1, YAP1, or ERBB2.

Assignments (1)
CONFIRMATORY LICENSE Recorded Jan 26, 2023
From: EMORY UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 062519/0215 →
Continuity (3)
Provisional Application 62718583 · Aug 14, 2018
Provisional Application 62813467 · Mar 4, 2019
Related Publication 20210299078A1 · Sep 30, 2021
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