ENOLASE 1 (ENO1) COMPOSITIONS AND USES THEREOF
The invention provides compositions comprising Eno1 and a muscle targeting peptide, e.g, as a fusion protein, for delivery of Eno1 to a muscle. The Eno1 may contain one or more added cysteine residues which are covalently attached to a biocompatible polymer (e.g. polyethylene glycol). Further, the invention provides a method for normalizing blood glucose in a subject with elevated blood glucose, comprising administering to the subject enolase 1 (Eno1), thereby normalizing blood glucose in the subject. The invention also provides methods of treating one or more conditions including impaired glucose tolerance, insulin resistance, pre-diabetes, and diabetes, especially type 2 diabetes in a subject, comprising administering to the subject enolase 1 (Eno1), thereby treating the condition in the subject.
1 . An Eno1 molecule comprising an Eno1 polypeptide or a fragment thereof and a muscle targeting peptide, wherein the Eno1 polypeptide or fragment thereof is covalently attached to the muscle targeting peptide.
2 - 28 . (canceled)
29 . A pharmaceutical composition comprising the Eno1 molecule of claim 1 .
30 . A nucleic acid encoding the Eno1 molecule of claim 1 .
31 . An expression vector comprising the nucleic acid of claim 30 .
32 . An Eno1 molecule comprising an Eno1 polypeptide or a fragment thereof, wherein the Eno1 polypeptide or fragment thereof comprises at least one added cysteine residue.
33 - 54 . (canceled)
55 . A pharmaceutical composition comprising the Eno1 molecule of claim 32 .
56 . A nucleic acid encoding the Eno1 molecule of claim 32 .
57 . An expression vector comprising the nucleic acid of claim 56 .
58 - 60 . (canceled)
61 . A method of decreasing blood glucose in a subject with elevated blood glucose, the method comprising administering to the subject the pharmaceutical composition of claim 29 , thereby decreasing blood glucose in the subject.
62 . A method of increasing glucose tolerance in a subject with decreased glucose tolerance, the method comprising administering to the subject the pharmaceutical composition of claim 29 , thereby increasing glucose tolerance in the subject.
63 . A method of improving insulin response in a subject with decreased insulin sensitivity and/or insulin resistance, the method comprising administering to the subject the pharmaceutical composition of claim 29 , thereby improving insulin response in the subject.
64 . A method of treating diabetes in a subject, the method comprising administering to the subject the pharmaceutical composition of claim 29 , thereby treating diabetes in the subject.
65 . The method of claim 64 , wherein the diabetes is type 2 diabetes or type 1 diabetes.
66 . The method of claim 64 , wherein the diabetes is pre-diabetes.
67 . A method of decreasing an HbA1c level in a subject with an elevated Hb1Ac HbA1c level, the method comprising administering to the subject the pharmaceutical composition of claim 29 , thereby decreasing the HbA1c level in the subject.
68 . A method of improving blood glucose level control in a subject with abnormal blood glucose level control, the method comprising administering to the subject the pharmaceutical composition of claim 29 , thereby improving blood glucose level control in the subject.
69 . The method of claim 61 , wherein glucose flux in a skeletal muscle cell of the subject is increased.
70 . A method of increasing glucose flux in a subject, the method comprising administering to the subject the pharmaceutical composition of claim 29 , thereby increasing glucose flux in the subject.
71 . A method of increasing glycolytic activity or capacity in a skeletal muscle cell of a subject, the method comprising administering to the subject the pharmaceutical composition of claim 29 , thereby increasing glycolytic activity or capacity in a skeletal muscle cell of the subject.
72 . A method of increasing mitochondrial free fatty acid oxidation in a skeletal muscle cell of a subject, the method comprising administering to the subject the pharmaceutical composition of claim 29 , thereby increasing mitochondrial free fatty acid oxidation in a skeletal muscle cell of the subject.
73 - 78 . (canceled)