COMPOSITIONS COMPRISING ENO1 AND THEIR USE IN METHODS OF TREATING OBESITY OR OVERWEIGHT AND REDUCING WEIGHT GAIN
The invention provides a method for reducing or preventing body weight gain in a subject comprising administering to the subject enolase 1 (Eno1). The invention also provides methods of treating obesity, and of reducing body weight in a subject afflicted with an overweight condition, comprising administering to the subject enolase 1 (Eno1). In certain embodiments, the body weight gain, obesity or overweight condition is caused by a therapeutic treatment, such as a diabetic drug. In certain methods of the invention, the Eno1 is delivered to muscle.
1 . A method of treating obesity in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a composition comprising Eno1 or a fragment thereof, thereby treating obesity in the subject.
2 . The method of claim 1 , wherein the subject is suffering from obesity, and wherein the obesity is associated with type 2 diabetes, type 1 diabetes, or pre-diabetes.
3 . The method of claim 1 , wherein the obesity is caused or exacerbated by a therapeutic treatment.
4 . The method of claim 3 , wherein the therapeutic treatment is selected from the group consisting of therapeutic agents for the treatment of diabetes, antipsychotic agents, antidepressants, mood stabilizers, anticonvulsants, steroid hormones, prednisone beta-blockers, oral contraceptives, antihistamines, HIV antiretroviral drugs, antiseizure and antimigraine drugs, protease inhibitors, antihyperlipemic agents, hypotensive or antihypertensive agents, anti-obesity agents, diuretics, chemotherapeutic agents, immunotherapeutic agents, and immunosuppressive agents.
5 . The method of claim 3 , wherein the therapeutic treatment comprises a therapeutic agent for the treatment of diabetes.
6 . A method of reducing body weight in a subject afflicted with an overweight condition, comprising administering to the subject a therapeutically effective amount of a composition comprising Eno1 or a fragment thereof, thereby reducing body weight in the subject.
7 . The method of claim 6 , wherein the subject has a body mass index of between 25 kg/m 2 and 30 kg/m 2 .
8 . The method of claim 6 , wherein the overweight condition is caused or exacerbated by a therapeutic treatment.
9 . The method of claim 8 , wherein the therapeutic treatment is selected from the group consisting of therapeutic agents for the treatment of diabetes, antipsychotic agents, antidepressants, mood stabilizers, anticonvulsants, steroid hormones, prednisone beta-blockers, oral contraceptives, antihistamines, HIV antiretroviral drugs, antiseizure and antimigraine drugs, protease inhibitors, antihyperlipemic agents, hypotensive or antihypertensive agents, anti-obesity agents, diuretics, chemotherapeutic agents, immunotherapeutic agents, and immunosuppressive agents.
10 . The method of claim 8 , wherein the therapeutic treatment is a therapeutic agent for the treatment of diabetes.
11 . A method of reducing or preventing body weight gain in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising Eno1 or a fragment thereof, thereby reducing or preventing body weight gain in the subject.
12 . The method of claim 11 , wherein the subject is in need of a therapeutic treatment that induces weight gain.
13 . The method of claim 11 , wherein the subject is undergoing a therapeutic treatment that induces weight gain.
14 . The method of claim 13 , wherein the therapeutic treatment is selected from the group consisting of therapeutic agents for the treatment of diabetes, antipsychotic agents, antidepressants, mood stabilizers, anticonvulsants, steroid hormones, prednisone beta-blockers, oral contraceptives, antihistamines, HIV antiretroviral drugs, antiseizure and antimigraine drugs, protease inhibitors, antihyperlipemic agents, hypotensive or antihypertensive agents, anti-obesity agents, diuretics, chemotherapeutic agents, immunotherapeutic agents, and immunosuppressive agents.
15 . The method of claim 12 , wherein the therapeutic treatment is a therapeutic agent for the treatment of diabetes.
16 . The method of claim 5 , wherein the therapeutic agent for the treatment of diabetes is selected from the group consisting of sulfonylureas, insulin, GLP-1 receptor agonists, DPP-4 inhibitors, metformin, and rosiglitazone.
17 . The method of claim 16 , wherein the therapeutic agent for the treatment of diabetes is rosiglitazone.
18 - 19 . (canceled)
20 . The method of claim 1 , wherein administering the composition comprising Eno1 or the fragment thereof to the subject reduces body weight by at least 5% relative to a control.
21 . The method of claim 1 , wherein administering the composition comprising Eno1 to the subject reduces body mass index (BMI) by at least 5% relative to a control.
22 . The method of claim 1 , wherein the subject has any one or more of elevated blood glucose, decreased glucose tolerance, decreased insulin sensitivity and/or insulin resistance, diabetes, elevated Hb1Ac level, and abnormal blood glucose level control.
23 . The method of claim 1 , further comprising selecting a subject having any one or more of obesity, elevated blood glucose, decreased glucose tolerance, decreased insulin sensitivity and/or insulin resistance, diabetes, elevated Hb1Ac level, and abnormal blood glucose level control.
24 . The method of claim 1 , wherein the subject is human.
25 . The method of claim 1 , wherein the Eno1 or fragment thereof comprises an Eno1 polypeptide or a fragment thereof.
26 . The method of claim 1 , wherein the Eno1 or fragment thereof comprises an Eno1 nucleic acid or a fragment thereof.
27 . The method of claim 26 , wherein the Eno1 nucleic acid or fragment thereof is present in an expression vector.
28 . The method of claim 25 , wherein the Eno1 polypeptide or fragment thereof is biologically active.
29 . The method of claim 28 , wherein the Eno1 polypeptide or fragment thereof has at least 50%, 60%, 70%, 80% or 90% activity of a purified endogenous human Eno1 polypeptide.
30 . The method of claim 1 , wherein the Eno1 is human Eno1.
31 . The method of claim 1 , wherein the composition is for delivery to a muscle cell.
32 . The method of claim 25 , wherein the composition further comprises a muscle targeting moiety.
33 . The method of claim 32 , wherein the Eno1 polypeptide or fragment thereof and the muscle targeting moiety are present in a complex.
34 . The method of claim 32 , wherein the muscle targeting moiety is a muscle targeting peptide.
35 . The method of claim 33 , wherein the complex further comprises a linker.
36 . The method of claim 35 , wherein the linker is selected from the group consisting of a covalent linker, a non-covalent linkage, and a reversible linker.
37 . The method of claim 35 , wherein the linker comprises a protease cleavage site.
38 . The method of claim 33 , wherein the Eno1 is released from the complex upon delivery to a muscle cell.
39 . The method of claim 33 , wherein the Eno1 and the muscle targeting peptide are present in the complex at a ratio of about 1:1 to about 1:30.
40 . The method of claim 1 , wherein the composition further comprises a liposome.
41 . The method of claim 1 , wherein the composition comprising Eno1 or a fragment thereof is administered orally.
42 . The method of claim 1 , wherein the composition comprising Eno1 or a fragment thereof is administered parenterally.
43 . The method of claim 42 , wherein the composition comprising Eno1 or a fragment thereof is administered by a route selected from the group consisting of intramuscular, intravenous, and subcutaneous.