Treatment of non-alcoholic fatty liver disease
The Applicant has discovered that the peptide of SEQUENCE ID NO: 1 (WKDEAGKPLVK) mediates changes in key biomarker activities associated with NASH (Table 1), and that the peptide is capable of penetrating HepG2 liver cells in a hepatic cell penetration assay (FIG. 1 ). In addition, the Applicant demonstrates that treatment with pep_260 (SEQ ID 1) for 44 days significantly relieves macro-vesicular steatosis in obese diabetic KKAy mice (FIG. 2 ) In a first aspect, the invention relates to the use of a peptide comprising SEQUENCE ID NO: 1, or a functional (or therapeutically effective) variant or functional fragment of SEQUENCE ID NO: 1 (hereafter “peptide active agent” or “peptide of the invention”), in a method for the treatment or prevention of non-alcoholic fatty liver disease (NAFLD), in particular non-alcoholic steatohepatitis (NASH), in a mammal.
1. A method for the treatment of non-alcoholic fatty liver disease (NAFLD) in a mammal having NAFLD, the method comprising:
administering:
(a) a peptide having up to 50 amino acids and comprising SEQ ID NO: 1, or
(b) a therapeutically effective variant of SEQ ID NO: 1 comprising 1 to 5 alterations compared with SEQ ID NO: 1, in which each alteration is independently selected from insertion of an amino acid, addition of an amino acid, deletion of an amino acid, and conservative substitution of an amino acid,
to the mammal.
2. The method of claim 1 wherein the non-alcoholic fatty liver disease is non-alcoholic steatohepatitis (NASH).
3. The method of claim 1 wherein the peptide consists of SEQ ID NO: 1.
4. The method of claim 1 wherein the method further comprises a step of administering a diabetes or obesity drug.
5. The method of claim 1 , wherein one or more of the amino acids of SEQ ID NO: 1 are substituted with D-forms of the amino acids.
6. The method of claim 1 wherein at least two residues selected from residues 1, 2, 5, 10 and 11 of SEQ ID NO: 1 are substituted with a D-form of the amino acid.
7. The method of claim 1 , wherein at least three or four residues selected from residues 1, 2, 5, 10 and 11 of SEQ ID NO: 1 are substituted with a D-form of the amino acid.
8. The method of claim 1 , wherein the peptide comprises SEQ ID NO: 2.
9. The method of claim 1 , wherein the peptide is cyclised.
10. The method of claim 1 , wherein the peptide is a cyclised peptide of SEQ ID NO: 3.