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US 12,447,199 B2Granted
System and methods to promote cellular regeneration following ischemia
AssigneeGeorgia State University Research Foundation, Inc.
InventorZhi-Ren Liu
Life of this patent
Estimating the term…
Abstract
Systems and methods for promoting cellular regeneration in ischemic tissue through administration of pyruvate kinase M2 or a substantially similar therapeutic to the ischemic tissue are disclosed herein.
Claims8
A method of promoting cellular regeneration in an ischemic tissue or tissue damaged by ischemia in a subject, comprising:
- administering a composition containing a modified pyruvate kinase M2 (PKM2) protein according to sequence identity to SEQ ID NO:5 to the ischemic tissue or the tissue damaged by ischemia, wherein the modified PKM2 possesses mutations differing from the wild-type PKM2 sequence stabilize in a dimer form;
- the modified pyruvate kinase M2 (PKM2) protein is not a constitutive dimer of PKM2;
- the modified PKM2 comprises three amino acid substitutions R399E, K422A, and N523A based on the sequence of wild-type human PKM2 (SEQ ID NO:
- 4) that result in a stabilized dimer form of PKM2 relative to and different from wild-type PKM2;
- the modified pyruvate kinase M2 (PKM2) protein promotes cellular regeneration in ischemic tissue or tissue damaged by ischemia;
- the modified pyruvate kinase M2 (PKM2) protein is a dimer;
- the
- modified PKM2 is human PKM2;
- and
- the modified pyruvate kinase M2 (PKM2) protein enhances cellular regeneration over new blood vessel formation to a greater extent than would be achieved solely through new blood vessel formation.
7 more elements
A method of promoting cellular regeneration in ischemic tissue or tissue damaged by ischemia in a subject, comprising:
- administering a composition containing a modified pyruvate kinase M2 (PKM2) protein to the ischemic tissue or tissue damaged by ischemia, wherein the modified PKM2 protein (a) has mutations that stabilize it in a dimer form, differing from the wild-type PKM2 sequence, (b) is not a constitutive dimer of PKM2, (c) has a sequence according to SEQ ID NO:
- 5 comprising three amino acid substitutions R399E, K422A, and N523A based on the sequence of SEQ ID NO:
- 4 that results in a stabilized dimer form compared to the wild-type PKM2, and (d), promotes and enhances cellular regeneration within the damaged tissue;
- wherein the enhanced cellular regeneration promotes tissue repair and cell proliferation within the ischemic tissue or tissue damaged by ischemia;
- the modified pyruvate kinase M2 (PKM2) protein forms a dimer at a concentration greater than 1 μM;
- the modified pyruvate kinase M2 (PKM2) protein enhances cellular regeneration to a greater extent than would be achieved solely through new blood vessel formation;
- and the subject is in need of cellular regeneration.
4 more elements
Dependencies are inferred from the claim text.