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ARC-520 Hepatocyte Targeted Therapy / Powerful HBV Silencer by Arrowhead Reasearch
Hey everyone,
Following the press release, I took studyforhope suggestion and read the paper on this new therapy. There's a lot to read and understand but here is what I got from my first pass (below is the link for the paper).
1. The therapy interferes with the RNA of the viral proteins: HbsAg, HBV DNA, and HbeAg
2. The therapy has shown in mice and non-human primates to have a powerful effect on reducing HbsAg, HBV DNA, and HbeAg (numbers of 90%+ from a single dose)
3. More importantly Arrowhead has found a very efficient way to deliver 99% of the drug directly to Hepatocytes which was previously a big concern due to toxicity.
4. The hope of this therapy is to inhibit the viral proteins to help the immune system recover and build immunity.
5. Many safety markers had no increase for example ALT.
6. They hope to provide this as a monthly injection.
Seems very promising. Looking forward to discussion on this from the community.
http://www.nature.com/mt/journal/vaop/ncurrent/full/mt201331a.html
Following the press release, I took studyforhope suggestion and read the paper on this new therapy. There's a lot to read and understand but here is what I got from my first pass (below is the link for the paper).
1. The therapy interferes with the RNA of the viral proteins: HbsAg, HBV DNA, and HbeAg
2. The therapy has shown in mice and non-human primates to have a powerful effect on reducing HbsAg, HBV DNA, and HbeAg (numbers of 90%+ from a single dose)
3. More importantly Arrowhead has found a very efficient way to deliver 99% of the drug directly to Hepatocytes which was previously a big concern due to toxicity.
4. The hope of this therapy is to inhibit the viral proteins to help the immune system recover and build immunity.
5. Many safety markers had no increase for example ALT.
6. They hope to provide this as a monthly injection.
Seems very promising. Looking forward to discussion on this from the community.
http://www.nature.com/mt/journal/vaop/ncurrent/full/mt201331a.html
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They cant sell that heptech here without prescription. What is the alternative brand called? I lost my bookmarks.
I looked at.heptech http://www.hepatitistechnologies.com/store/product/68408/HepTech good list of ingredients mainly as was explained to me good to fight oxydative stress, but silicon dioxide use is no good i think.
I looked at.heptech http://www.hepatitistechnologies.com/store/product/68408/HepTech good list of ingredients mainly as was explained to me good to fight oxydative stress, but silicon dioxide use is no good i think.
Hi,
Stef2011, what do you think about this new drug? DOes it appear to be as effective as REP 9AC or MYcludex?
thanks
Stef2011, what do you think about this new drug? DOes it appear to be as effective as REP 9AC or MYcludex?
thanks
if it is not visible by ultrasound you are eraly cirrhosis, dont worry
mine was extremely easy to see on US and all full of nodules, small but full of it
mine was extremely easy to see on US and all full of nodules, small but full of it
Stefan, I appreciate you - thanks. My last u/s was nearly a year ago -and no, there were no visible nodules then. I am having another u/s done this month...and will let you know the results. However also I have been told that often cirrhosis will not be visible on u/s until it is advanced. I am encouraged by the fact that my platelets are still approx 180K....so perhaps my disease is not as advanced as I fear -
in my case i just noticed effect on brain (confusion, difficulty in concentration....), i think this is the main effect you can feel on early decompensation.if all paramenters of liver function are good i think it is just a matter of time for heptech to work, remember you ll see an effect on yearly base not few months
do youalso have nodules on US image?
Thanks. To clarify - I am compensated in the sense that all liver functions are still good. Platelets approx 180K (low end of normal). I have no debilitating fatigue - indeed no debilitating symptoms of any kind. I have, however, developed palmar erythema and other skin stigmata - and have mild anemia. Also mild muscle loss - so obviously I am at least beginning to decompensate. Naturally I am wanting to do everything possible to stop progression (if possible...or at the very least, slow it down). Thankfully I am long-term SVR so I have no HCV virus.
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Herpes sores blister, then burst, scab and heal.
Herpes spreads by oral, vaginal and anal sex.
STIs are the most common cause of genital sores.
Condoms are the most effective way to prevent HIV and STDs.
PrEP is used by people with high risk to prevent HIV infection.
But the sentence that i outlined from the paper holds a much more likely pitfall to this therapy.
The target message RNA has to be a very precise sequence for the silencing to work. Thus any mutation in this sequence will tender the drug ineffective and unresponsive in the cell containing the mutated cccDNA. We must assume such mutations preexist and will give the respective HBV genome a selective advantage. It will spread quickly and repopulate the liver with therapy resistent progeny. No more supression, a happy virus and a drop in stock prices. Since there are so many places where it can mutate it will likely do so.
To see problem number 2 you need to go the place where they discuss the magnitude of the surface antigen suppression that can be expected.
In this context it needs to be mentioned that the replicor drug suppresses the antigen particle production by a factor better than 10000! fold. It is likely that a very high degree of surface antigen removal is necessary to remove the tcell tolerizing effect.
The famous idea, that a reduction under 500 units is sufficient to rekindle very likely does NOT apply in this setting. But this is complicated topic in itself.
The next problem that looms is not so apparent.
Consider the reason, why the precore mutant with elimination of the e antigen reduces the chance that the infected cell can be eliminated dramatically. It is the lack of the cytosolic processing of the e antigen carrying also the class I core epitopes through the proteasome to the MHC CLASS I presenting molecules on the hepatocte surface where the cd8+ CTL engage with their Cognate T cell receptors.
What would happen if the surface antigen production is shut down due to messenger RNA silencing? How can the now available surface antigen epitope specific cd8+ T cells come and recognize the infected cell? It is as if the critical markers of infection are now turned off.
The Replicor drug does not touch the primary sythesis of the surface antigen, it only blocks the formation of the globular structure on the ER membrane. Thus proteasome processing remains fully intact and effective. All the lights are on and the infected cell is visible to the searching cd8+ Tcells, resulting in targeted lysis and hyperintensive localized IFN gamma bursts, that clean up the neigborhood by noncytolytic cccDNA elimination.