Theratechnologies Inc T.TH

liver fibrosis progression via VEGF-A

[jeffm34]

https://portlandpress.com/clinsci/article-abstract/129/8/699/71291

[jeffm34]

TGF-β1 (transforming growth factor β1) was found to be mainly responsible for the up-regulation of CD147. Bioinformatic and experimental data suggest a functional link between CD147 expression and VEGF-A (vascular endothelial growth factor A)/VEGR-2 (VEGF receptor 2) signalling-mediated angiogenesis in fibrotic liver tissues. Tesamorelin decreases TGF-B1 which appears to down regulate CD147 which

[realitycheck4u]

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[Wino115]

The close relationship between the three genes is interesting. I didn't see any poster from that AASLD presentation or a paper so this fills in some of the blanks on how those three work together.  Here's another interesting statement from your find: "...it was significantly associated with fibrosis stage...."  and that "..blocking it attenuated liver fibrosis

[realitycheck4u]

This post has been removed in accordance with Community Policy

[Wino115]

As I think about this, one part stands out to me --the fact that there is a relationship between the overexpression of these genes and the level of fibrosis.  It explains a lot behind the numbers in the Phase 2 NAFLD trial.   I think it's important in showing how a drug can work that the cellular change your drug is acting on is done on a genetic trait that is abundant in the damaged

[qwerty22]

I think you're right that the specifics of thtx's patients matter somewhat. Yes they are full nafld spectrum rather than just late stage NASH but I think it goes much further. My memory is the mean BMI for THTX study was 30, that's roughly means maybe half were obese and half only fall in the overweight category. For mdgl's trial the average bmi was 35, so likely all obese. The

[qwerty22]

Also just saw this abstract that's just out. https://link.springer.com/article/10.1007/s13105-020-00777-7 PPAR drugs are another class of anti-NASH drugs. This paper suggests they work by affecting hepatic Stellate cells and down-regulating TGF-beta1 which is over-expressed during NASH. So potentially tesamorelin does what a PPAR drug does plus more, I think that's because GH/IGF-1

[Wino115]

I checked out Akeros research postings and one of the papers also mentions their Fibroblast Growth Factor (FGF) also downregulates TGFb1 and is mentioned as one of the key ways to lower liver fats.  It's on their website under research.  Given the success of just a few of these drugs on lowering liver fat more than 30% and they all seem to share a couple of these up and down

[qwerty22]

https://pubmed.ncbi.nlm.nih.gov/26592322/ This paper on their publication list? From the little I understand it seems to be showing the same role that's being shown in the PPAR paper. And the take home message is along the lines of your last sentence. TGF-b1 has been identified to have a central role in NASH progression, it's elevated in inflamed livers and it's suppressed by a