"You have got to be more positive dude! They are all moving, but they are limitations because it take time to determine toxicity and all the other stuff that can happen. GS-9620 is in phase I (or II since they are treating infected subjects), Myrcludex B is in being tried on HBV patients. Rep 9AC' is being tried on patients in combination with other drugs as presented the other day. ARC-520 is moving to IND next year and clinical trials after that. Trials will be coming and you'll have an opportunity to participate if you intend to do so. We're all in the same boat, but we got to make sure that the drugs work first in a statistically significant way. Until thorough studies are done, we can’t be sure"
I am trying to be positive but there is nothing to be positive about other then the Myrcludex attempt for wider clinical trials on a more or less good schedule.. I just hope they approve it in Russia next week so everyone can get help.
GS9620 trial did not take me :(. Turns out in the end I was on the wrong drug. Although they promised. And I waited. When it came to it I was told I have to be 3 months on TDF in order to enter. Now, what do you call this? Responsible people other there, good doctors? I say it *****!!!
next Replicor people.. Did they come to this forum, did they reply to us as to how we can get the drug? Again NO.. So what is all this secrecy about these medications? HBV treatment is what a classified military project now?
So now I am supposed to be excited about ARC-520... which is what years away? Of course it is something to look forward to.. but till these companies start acting more responsibly and think that there are 300 million people some of which with are in advance stages of liver disease and are in need of an immediate help. Till then all this info can be treated as marketing.
HBV is a hurricane that destroys the liver. It is a human disaster. And these companies have all these agents available now, and they say legally they can't use them. Does that makes sense? Staying alive with hbv for 3-5 years is a challenge. Most of us live in 6 months increments. Do they know what it is it like?
it is goes kinda like this in comparison. If people that were damaged by the hurricane on the east coast of the US, were told > but Oh well you have to wait 3-4 years while we sort things out here legally and see if it really works. Replicor stuff cleared HBV in 10 of 12 people in 7-12 weeks. And that is still cannot be called a cure. Or an unfinished drug.
Toxicity they worry about your say? What about toxicity from taking antivirals indefinitely, anybody worries about this? They don't even look at available HIV treatment data what nucs do.. why antivirals cause high blood pressure and what can be done to reverse it?
The way I see it all the info they release about new drugs does not make us infected warm until these companies take a moral responsibility and start doing something that can save people now. Until they come here, their CEO's or press managers and have a dialog with the people. So red tape they face today in western countries can be lifted. And it can be lifted. Once there are enough voices.
There is 300 million of us, if we start making our voices heard on the internet - the public will force companies to makes changes. And make make doctors act more responsibly. I think we need the media to get involved in this. So they start paying attention to us.
Some people come here to collect info for their research teams it is obvious. But we the patients can't wait. If these companies don't even bother to come here and talk to us openly that means they are don't hold us in a very high regard.
The way I see it clinical trials for us, should be done on a military type schedule. And it is doable, to conduct clinical trials, on patients making adjustment as they go along.
That is why I raise these issues... because their good is really not good enough.
This concept has some chance to work. Provided enough suppression time is given, T cell recovery is possible, initially without sufficient targets to find.
Once you let the full synthesis start again, the targets become visible. There is one big problem however: the newly formed surface antigen will flood the body again and will be presented by all the macrophages and dendritic cells all over, leading to a new distraction, exhaustion and tolerization of the specific T cells. Remember the removal of infected cells takes time, 30 to 40 weeks with rep9ac.
At the start it might be better to have a viral load, btw, since virions are the best immune stimulators. Thus pretreating rep9ac with an antiviral might reduce immun vigor. On the other hand, starting with a high viral load might also lead to surface antigen epitope specific escape mutations, leaving behind a resistant population. The perfect answer to this dilemma is to simultaneously start rep9ac and Myrcludex, then existing mutations cannot spread and you can follow the vl as a clean indicator of infected cell removal.
Make sense to me. I wonder how the X protein is made available to the antigen presenting cells?
Well this leaves one final try. So ARC-520 can behave like oral antivirals in reducing viral load to undetectable with the added bonus that it can also reduce serum HBsAg. This will remove tolerance and restore HBV specific Tcells to full functionality. To overcome the problem of lack of Xmass tree lights on the surface of infected hepatocytes as these lights have been switched off, we can stop all treatments, thus allowing the virus to replicate again and turning on the Xmas tree lights again. But this tine, our Tcells are ready to strike back? Will this work? [This concept is being tested in a clinical trial in patients long term suppression of viral replication by Tenofovir]
The display of the x gene epitopes are expected to be of low efficiency, since the x protein is produced only in small amounts. Speculations of x directed Tcell responses are floating around from time to time however , in low quality publications.
The spontaneous and antiviral induced small number of surface antigen converters might well be converted due to the virtue of a remnant anti core Tcell response, possibly also due to variant HLA types that can use other classI core/eAg epitopes.
. As long as the surface antigen itself is high or even moderately high there is no way it can contribute to the Tcell response, due to its tolerizing effect. Thus these types of rare conversions are NOT a model for the replicor effect, where the surface antigen is drastically reduced to zero or almost zero by the drugs effect in the hepatocyte. Then the above mentioned effects will start up.
I want to add, that the surface antigen due to its ubiquitous engagement of dendritic cells and macrophages, also has an unspecific inhibitory effect on the immune response against unrelated HBV antigens. To put it simple, it keeps the presenting cells busy with crap. The respective papers typically show, that a relatively high concentration of surface antigen is needed to show this effect convincingly, thus the famous below 1000iU might be a threshold where this effect will substantially diminish, since it seems to be a mass effect, maybe coupled with a downregulatory effect of a more specific kind. Such an effect was more convincingly shown for the e-antigen.
I think that replicor tries to advance to a subcutaneous formulation, away from the intravenous infusions that they needed to use up to this point with both generations of their DNA preparations. An intravenous infusion lasting many hours once a week is not very feasable for a larger patient population, most doctors or hospitals would charge substantially for this service. The second contribution at the above oligonucleotide conference that stephencastlecrag saw might be a further important step in the direction of easier application, since the CaCl preparation will likely remove many of the unpleasant side effects hat make thus far multihours infusions necessary. Thus the final mode of application and subtype of the antigen release blocker to be used with greatest ease needs to be determined first, before larger scale trials and the huge capital investment for a larger phase II trial can be done. Hopefully, once the formulation has been optimized, a financial sponser powerful to move this incredible promising approach along will be found.
What a bummer. LOL. Thanks for the lesson..
I read that HBV specific Tcells response to HBV core, envelope, and X proteins. So how good is the display of X protein epitope by MHC Class I molecules.
In a paper by some Chinese scientists, they observed that "however the T cell responses in the seroclearance[S seroconversion in a group of 14 Chinese patients following antiviral treatment] group were almost exclusively to core antigens. Only a small number of low level response to envelope gene antigens were detected." So the scientists stated; "Thus our data did not provide clues to the cause of HBsAg seroconversion in this group of subjects." So surface antigen specific Tcells may not be that important in clearing the virus, casting doubt at the same time in understanding how REP9AC actually work.
Just my opinion as someone who does not know what he is talking about.