US 12,447,199 B2
System and methods to promote cellular regeneration following ischemia
Zhi-Ren Liu, Atlanta, GA (US)
Assigned to GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC., Atlanta, GA (US)
Appl. No. 16/766,227
Filed by GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION , INC., Atlanta, GA (US)
PCT Filed Nov. 21, 2018, PCT No. PCT/US2018/062213
§ 371(c)(1), (2) Date May 21, 2020,
PCT Pub. No. WO2019/104142, PCT Pub. Date May 31, 2019.
Claims priority of provisional application 62/589,451, filed on Nov. 21, 2017.
Prior Publication US 2020/0368329 A1, Nov. 26, 2020
Int. Cl. A61K 38/45 (2006.01)
CPC A61K 38/45 (2013.01) [C12Y 207/01004 (2013.01)] 8 Claims
 
1. 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.