Peptides for treatment and prevention of nonalcoholic fatty liver disease and fibrosis
The present invention relates to peptides for the treatment or prevention of nonalcoholic fatty liver disease (NAFLD), non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), hepatic steatosis (fatty liver), liver inflammation, cirrhosis, hepatocellular carcinoma or fibrosis, especially liver fibrosis.
1 . A peptide comprising:
(SEQ ID NO: 25)
VECTX X EKRVLA X ;
(SEQ ID NO: 26)
VECTM X EKXVLA X ;
(SEQ ID NO: 27)
VECTX X EKXVLA X ;
(SEQ ID NO: 28)
VECTX X EKXVLA X LDKXXFLTQLHS;
(SEQ ID NO: 29)
VECTM X EKRVLA X LDKXXFLTQLHS;
(SEQ ID NO: 30)
VECTX X EKRVLA X LDKPPFLTQLHS;
(SEQ ID NO: 31)
VECTM X EKXVLA X LDKPPFLTQLHS;
wherein the residues which are bold and underlined X are stapled and is any amino acid derivative suitable for stapling; and
wherein X is any amino acid except M, P and R.
2 . A pharmaceutical composition comprising a peptide according to claim 1 .
3 . The peptide of claim 1 , wherein said peptide comprises:
(SEQ ID NO: 26)
VECTM X EKXVLA X ;
(SEQ ID NO: 29)
VECTM X EKRVLA X LDKXXFLTQLHS;
(SEQ ID NO: 30)
VECTX X EKRVLA X LDKPPFLTQLHS;
or
(SEQ ID NO: 31)
VECTM X EKXVLA X LDKPPFLTQLHS.
4 . The peptide of claim 1 , said peptide decreasing Fatty Acid Transport Protein 2 (FATP2) expression in adipose tissue.
5 . A method of treating a disease selected from the group consisting of nonalcoholic fatty liver disease (NAFLD), non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), hepatic steatosis (fatty liver), liver inflammation, cirrhosis, hepatocellular carcinoma and fibrosis comprising the administration of a peptide according to claim 1 , or a pharmaceutical composition thereof, to a subject in need of treatment.
6 . The method of claim 5 , wherein the fibrosis is a liver fibrosis, liver cirrhosis, renal fibrosis, cardiac fibrosis, atrial fibrosis, endomyocardial fibrosis, old myocardial infarction, pulmonary fibrosis, cystic fibrosis, radio-induced lung fibrosis, vascular fibrosis, arterial fibrosis, brain fibrosis, myelofibrosis, arthrofibrosis, intestinal fibrosis, peritoneal fibrosis, retroperitoneal fibrosis or skin fibrosis.