Gene therapy compositions for use in the prevention and/or treatment of non-alcoholic fatty liver disease

Patent metadata

Field	Value
Publication number	US-2016354489-A1
Application number	US-201415024821-A
Country	US
Kind code	A1
Filing date	Sep 25, 2014
Priority date	Sep 26, 2013
Publication date	Dec 8, 2016
Grant date	—

Abstract

The present invention relates to the field of gene therapy and, more particularly, to methods for the prevention and/or treatment of non-alcoholic fatty liver disease (NAFLD). The viral vectors disclosed in the present invention are preferably parvoviral vector, more preferably adeno-associated vectors (AAV) containing the gene encoding Sirtuin 1 (Sirt1) in the prevention and/or treatment of NAFLD. The present invention also discloses the pharmaceutical compositions comprising the viral vector and the method of prevention and/or treatment of NAFLD and related diseases by the administration of said pharmaceutical compositions.

First claim

1 . A viral construct comprising a nucleotide sequence encoding Sirtuin 1 (Sirt1), or a functionally equivalent variant thereof, said viral construct being operably linked to a liver-specific promoter.

2 . The viral construct as defined in claim 1 which is a parvoviral construct.

3 . The viral construct as defined in claim 2 wherein the parvoviral construct is an AAV construct.

4 . The viral construct as defined in claim 3 wherein the AAV construct is an AAV2, AAV5, AAV7, AAV8 or AAV9.

5 . The viral construct as defined in claim 3 wherein the AAV construct is an AAV8.

6 . The viral construct as defined in claim 1 , wherein the liver specific promoter is selected from: albumin promoter, phosphoenol pyruvate carboxykinase (PEPCK) promoter or alpha1-antitrypsin promoter.

7 . The viral construct as defined in claim 6 wherein the liver specific promoter is the alpha1-antitrypsin promoter.

8 . The viral construct as defined in claim 1 wherein Sirt1 corresponds to a human Sirt1.

9 . A virion comprising the viral construct as defined in claim 1 packaged inside a capsid and, optionally a lipidic envelope surrounding said capside.

10 - 12 . (canceled)

13 . A pharmaceutical composition comprising the viral construct as defined in claim 1 or the virion as defined in claim 9 and a pharmaceutically acceptable carrier.

14 - 15 . (canceled)

16 . A method for treating a disease selected from: non-alcoholic fatty liver disease (NAFLD), insulin resistance, diabetes mellitus, metabolic syndrome or hyperlipidemia comprising administering the virion according to claim 9 or the pharmaceutical composition according to claim 13 .

17 . The method according to claim 16 , wherein the disease is non-alcohol fatty liver disease (NAFLD).

Assignees

• Univ Barcelona Autonoma
• Univ Autònome De Barcelona

Inventors

• Bosch Tubert Fàtima
• VILÁPRATS Laia

Classifications

• C12Y305/01

  in linear amides (3.5.1) · CPC title

• C12N2750/14171

  Demonstrated in vivo effect · CPC title

• C12N9/80

  acting on amide bonds in linear amides {(3.5.1)} · CPC title

• C12N2750/14141

  Use of virus, viral particle or viral elements as a vector · CPC title

• C12N2750/14145

  Special targeting system for viral vectors · CPC title