HEPARIN-BINDING DOMAIN OF IGFBP-2 IN THE TREATMENT OF METABOLIC DISORDERS
The present technology generally relates to compounds, in particular peptides comprising the heparin-binding domain (HBD) of insulin-like growth factor binding protein-2 (IGFBP-2) for the modulation of metabolic disorders. The present technology also generally relates to uses of such compounds in methods for preventing and/or treating metabolic disorders and in compositions and formulations for such uses.
1 . A method for modulating a metabolic disorder in a subject; the method comprising: administering to the subject a therapeutically effective amount of a peptide consisting of: i) a heparin binding domain (HBD) as set forth in SEQ ID NO: 1 or an analog thereof; ii) a fragment of the peptide as set forth in i); or iii) a pharmaceutically acceptable salt of any one of the peptide as set forth in i) and ii).
2 . The method according to claim 1 , wherein the metabolic disorder is a disorder associated with impaired glucose metabolism.
3 . The method according to claim 1 , wherein the metabolic disorder is further associated with impaired insulin metabolism.
4 . The method according to claim 1 , wherein the metabolic disorder is further associated with impaired leptin metabolism.
5 . The method according to claim 1 , wherein the metabolic disorder is a rare genetic obesity disorder.
6 . The method according to claim 1 , wherein the metabolic disorder is syndromic obesity.
7 . The method according to claim 1 , wherein the metabolic disorder is a disorder associated with leptin receptor (LEPR) deficiency or with leptin deficiency.
8 . The method according to claim 1 , wherein the metabolic disorder is one or more of: hypoglycemia, hyperglycemia, carbohydrate intolerance, glucose intolerance, impaired fasting glucose, impaired glucose tolerance, carbohydrate-lipid metabolism disturbance, hyperinsulinemia, Type IV hyperlipoproteinemia, insulin resistance, diabetes Type I, diabetes Type II, obesity; impaired beta cell function, acromegaly; a disorder associated with impaired melanocortin-4 (MC4) signaling pathway, a disorder associated with leptin receptor (LEPR) deficiency, a disorder associated with LEPR mutations, leptin receptor-related monogenic Obesity, syndrome of extreme insulin resistance, proopiomelanocortin (POMC) deficiency, POMC heterozygous, Alström syndrome, Bardet-Biedl syndrome (BBS), Donohue syndrome (leprechaunism), Rabson-Mendenhall syndrome, syndrome of extreme insulin resistance type A, syndrome of extreme insulin resistance type B, syndrome of extreme insulin resistance type C, HAIR-AN, Poly cystic Ovary syndrome (PCOS), congenital lipodystrophy syndromes, Beradinelli-Seip syndrome, acquired lipodystrophy syndromes, generalized lipodystrophy, and partial lipodystrophy.
9 . The method according to claim 1 , wherein the HBD is HBD1.
10 . The method according to claim 1 , wherein the peptide is pegylated.
11 . The method according to claim 1 , wherein the peptide is acylated.
12 . The method according to claim 1 , wherein the peptide is cyclic.
13 . The method according to claim 1 , wherein the analog thereof is a conservative analog thereof.
14 . The method according to claim 1 , wherein the analog thereof is a structural analog thereof, a functional analog thereof, or both.
15 . The method according to claim 1 , wherein the peptide is as set forth in SEQ ID NO: 73 or an analog thereof.
16 . The method according to claim 1 , wherein the peptide is as set forth in: SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO:13, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 22, SEQ ID NO: 23, SEQ NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ. ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ. ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113 or any analog thereof.
17 . (canceled)
18 . The method according to claim 1 , wherein the therapeutically effective amount is from about 0.01 μg to about 100 mg/kg.
19 . The method according to claim 1 , wherein the therapeutically effective amount is from about 0.3 mg/kg to about 3 mg/kg.
20 .- 26 . (canceled)
27 . The method of claim 1 , further improving glucose control in the subject, the method comprising: administering to the subject a therapeutically effective amount of a peptide consisting of: i) a heparin binding domain (HBD) as set forth in SEQ ID NO: 1 or an analog thereof; ii) a fragment of the peptide as set forth in i); or iii) a pharmaceutically acceptable salt of any one of the peptide as set forth in i) and ii).
28 . (canceled)
29 . The method of claim 1 , further improving insulin sensitivity in the subject, the method comprising: administering to the subject a therapeutically effective amount of a peptide consisting of: i) a heparin binding domain (HBD) as set forth in SEQ ID NO: 1 or an analog thereof; ii) a fragment of the peptide as set forth in i); or iii) a pharmaceutically acceptable salt or any one of the peptide as set forth in i) and ii).
30 . (canceled)