Granted Patent
B2
US 12,661,384 · App. 18/059,621 · Granted Jun 23, 2026
Methods for inducing cell division of postmitotic cells
A61K38/1709A61K35/30A61K35/34A61K35/36A61K35/39A61K38/45A61P9/10C12N5/06C12Y207/11022A61K35/00A61K2300/00C12N2310/111
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Abstract
The present disclosure provides methods for inducing cell cycle reentry of postmitotic cell. The present disclosure further provides cells and compositions for treating diseases, such as cardiovascular diseases, neural disorders, hearing loss, and diabetes.
Claims (16)
1 . A method of treating myocardial infarction (MI) in a subject in need thereof, comprising administering to the subject effective amounts of:
a) a cyclin-dependent kinase-4 (CDK4);
b) a cyclin D1 (CCND1); and
c) a TGF-β inhibitor, a Wee1 inhibitor, or both.
2 . The method of claim 1 , comprising administering a viral vector comprising a polynucleotide encoding the CDK4 and the CCND1.
3 . The method of claim 1 , comprising administering a first viral vector comprising a polynucleotide encoding the CDK4 and a second viral vector comprising a polynucleotide encoding the CCND1.
4 . The method of claim 1 , wherein the method comprises administering a TGF-β inhibitor and the TGF-β inhibitor is SB431542.
5 . The method of claim 1 , wherein the method comprises administering a TGF-β inhibitor and wherein the TGF-β inhibitor is dexamethasone.
6 . The method of claim 1 , wherein the method comprises administering both a TGF-β inhibitor and a Wee1 inhibitor.
7 . The method of claim 6 , wherein the TGF-β inhibitor is SB431542.
8 . The method of claim 6 , wherein the Wee1 inhibitor is MK1775.
9 . The method of claim 6 , wherein the TGF-0 inhibitor is SB431542 and the Wee1 inhibitor is MK1775.
10 . The method of claim 9 , wherein the method promotes cardiac cell proliferation.
11 . The method of claim 10 , wherein cardiac cell proliferation is assayed by increase in phospho-histone H3 (PHH3) staining of cTnT+ cells.
12 . The method of claim 10 , wherein cardiac cell proliferation is assayed by increase in 5-ethynyl-2′-deoxyuridine (EdU) staining of cTnT+ cells.
13 . The method of claim 9 , wherein the method decreases scar size after MI.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 6, 2022
From: MOHAMED, TAMER M.A.; SRIVASTAVA, DEEPAK
To: THE J. DAVID GLADSTONE INSTITUTES, A TESTAMENTARY TRUST ESTABLISHED UNDER THE WILL OF J. DAVID GLADSTONE
Reel/Frame 062001/0432 →
Continuity (5)
Continuation
15564752
Provisional Application
62151321
· Apr 22, 2015
Provisional Application
62144244
· Apr 7, 2015
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