Peptides for treatment and prevention of nonalcoholic fatty liver disease and fibrosis

A technology of adipose tissue and peptide sequences, which is applied in the treatment of fibrosis, nonalcoholic steatohepatitis, and hepatic steatosis, and can solve problems such as unsuccessful and insufficient effects

Active Publication Date: 2020-07-17
UNIVERSITY OF STRASBOURG +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Several compounds are known to treat fibrosis, but the effects are insufficient
Therefore, attempts to develop clinically effective fibrosis have been unsuccessful, and a treatment for fibrosis still needs to be found

Method used

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  • Peptides for treatment and prevention of nonalcoholic fatty liver disease and fibrosis
  • Peptides for treatment and prevention of nonalcoholic fatty liver disease and fibrosis
  • Peptides for treatment and prevention of nonalcoholic fatty liver disease and fibrosis

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0265] Example 1: Effect of Adipose Tissue-Targeted PATAD Treatment on Expression Levels of Key Fatty Acid Transporters and Receptors 11 Days Post-Injection

[0266] Since subcutaneous injection of PATAD is involved in restoration of glucose absorption in adipose tissue, the inventors measured all 6 isoforms of FATP(1-6) (fatty acid transporter 1-6) and 4 of FFAR (free fatty acid receptor) Expression levels of the isoforms to assess any effects on these genes.

[0267] Interestingly, PATAD injection caused an extremely specific and dramatic decrease in FAPT2 in adipose tissue, such that the effect of PATAD treatment was directly related to the decrease in FATP2 expression ( Figure 1A ). Since it was previously shown that PATAD peptides do not circulate in vivo, that their effects are limited to adipose tissue, and also based on their mechanism of action by interfering with ALMS1-PKC interactions, the new role of PATAD in adipose tissue is to reduce FATP2. The expression leve...

example 2

[0268] Example 2: ADPIF peptide is more active than PATAD peptide in reducing FATP2 expression level in adipose tissue

[0269] Mice were injected with a single dose of scrambled peptide or PATAD or ADPIF. Eleven days after injection, mice were euthanized and adipose tissue was sampled for RNA extraction followed by real-time PCR. FATP2 expression levels were similar to lean controls, while PATAD, although effective in reducing FATP2 expression levels in adipose tissue, was less effective than ADPIF ( Figure 2A ).

example 3

[0270] Example 3: ADPIF effectively increases circulating levels of GLP-1 11 days after adipose tissue injection.

[0271] Mice were injected with a single dose of scrambled peptide or PATAD or ADPIF. Eleven days after injection, mice were euthanized and plasma was obtained and used to determine circulating GLP1 in mice with the indicated treatments. Both PATAD and ADPIF restored high circulating levels of GLP1, with ADPIF causing a greater increase than PATAD ( Figure 2B ).

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PUM

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Abstract

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.

Description

technical field [0001] The present invention relates to the field of medicine. More specifically, the invention relates to the treatment of liver diseases, especially hepatic steatosis, especially non-alcoholic steatohepatitis, and the treatment of fibrosis. Background technique [0002] NAFLD (Non-Alcoholic Fatty Liver Disease), defined as the hepatic accumulation of triglycerides in liver cells in the absence of any other etiology of liver disease, is the most common cause of chronic liver disease in the Western world. Its clinical histologic phenotype ranges from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), characterized by liver inflammation and progressive fibrosis leading to cirrhosis and end-stage liver disease and hepatocellular carcinoma. [0003] In the general population, the prevalence of NAFLD is estimated to be 6% to 33%, while the prevalence of NASH is only 3%-5%, but cirrhosis associated with NASH has become the second leading indi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/04A61K38/06A61K38/07A61K38/17C07K5/00C07K5/08C07K5/10C07K7/06C07K7/08C07K14/435A61P1/16C07K5/06
CPCA61K38/04A61K38/06A61K38/07A61K38/17A61P1/16C12N9/1205C12N9/1025C07K5/08C07K5/10C07K7/06C07K7/08A61K39/001162A61K38/00C12Y207/11013A61K38/45C12N9/12A61K38/16C07K14/00
Inventor 文森特·马里昂
Owner UNIVERSITY OF STRASBOURG
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