Entry inhibitors show promise as drugs

Entry inhibitors like REP9 AC and Myrcludex-B are promising as they are the only drugs that offer a complete CURE for Hepatitis B compared to immune modulators like Pegasys and Anti-virals like Entecavir... I think more research and concentration should be diverted to release inhibitor drugs as they seem to be promising and appropriate....

[miracle852]

I read somewhere that they may not allow those drug to come to market until 2017 when the patent of Viread and Barculade will expires. Don't know how far this is true and don't know how effectives are REP9 AC and Myrcludex-B also.

[stef2011]

effectives are REP9 AC and Myrcludex-B also.

they are the first cures for hbv, there are no other drugs, this will tell how they are acting blocking the marketing of these products.

they also have no toxicity and much more safer than all the other drugs for liver disease (calling them hbv drugs is very wrong and just mmisleading to sell those drugs).as you know the sides of:
entecavir, possible cancer promotion, possible virus mutations/resistance
tenofovir, bone mineral density, kidneys damage

i have noticed replicor has only private investors, nothing from drug makers.if we all start donating small amounts (we are millions of hbv carriers) we might even buy the company and make drug approval in asia and then ship the drug worldwide......

by the way do not send money to hbv foundations, they just steel money without any help to get these drugs

[stef2011]

make drug approval in asia and then ship the drug worldwide......

of course just a dream but not totally impossible, facebook and youtube can do miracles like this....

[StephenCastlecrag]

REP 9AC is now believed to inhibit the release of HBsAg from the infected liver cells and Mycrludex, on the other hand, is an entry inhibitor.

You can invest in Replicor, minimum amount is 25,000 Canadian dollar (50,000 is the preferred amount).

[vootoodoo]

Sounds good, but can it be achieved in reality...Replicor have been quiet recently. Anyone with any update from them?

[stef2011]

You can invest in Replicor, minimum amount is 25,000 Canadian dollar (50,000 is the preferred amount)........

oh my 25000 is really a lot, as investment it can only work if they dont care about US market and FDA, since FDA just preserves US drug makers intrest and will never approve it

on the other hand US is going bankrupt and asia getting rich, in the near future china/india may become the richest in the world (if not already) and also the most intrested in hbv cures, so also drug investments should go to asia soon

[miracle852]

Does anybody has contact info for the REP 9AC and Myrcludex-B people...email, phonenumber etc. We can call and contact them and see how to carry the campaign for it. I can't believe, there could be a cure for an infection and some people will just keep it away, allow people to die just because of monetary gain.
Why is minimum investment that high? 25,000 or $50,000 CD is a lot of money?

[miracle852]

How much clinical trials do we have for these drugs also? How successful are they?

[stef2011]

i think 2 clinical trial in india paid by researchers...not even the company because of luck of money
they choosen the worst candidates with hbeag pos and very high hbvdna.hbsag cleared and hbsab antibody as early as 7 days and as late as 15weeks.

a combo of antivirals will make this a bomb because it is possible to have hbsag mutants so it must be comboed interferon or nucs

no sides reported, i think hbeag negative needs to be checked, they only had one in the trials and it didn t respond

[StephenCastlecrag]

Replicor is not listed on the stock exchange, therefore it raises fund its own way. It is not structured to deal with small investors. My understanding is that, the company is funded entirely by its investors many of whom are scientists.

Replicor's website site is: www.replicor.com.

Mycrludex is from the research lab of Prof Stephen Urban:


Stephan Urban
Head of Hepatitis B Research Group

Phone: [phone]
Fax: [phone]

Stephan_Urban***@****-heidelberg.de

[vijik]

guys in india too MNC pharma's has strong presence. Ranbaxy-daichi,piramal-abbott and so on. Last week, in business line daily, they published a detailed report about drug prices in front page itself. The shocking news is that immediately after the every greedy-MNCs acquiring indian companies, they steeply  increased the drug prices. So the Government here considering to control the prices by restricting the doctors to stay away from prescribing the brand name, and instead govt ask them to notify only the chemical  compound in prescription. So you can get prescribed, say for if fever, only paracetamal instead of crocin or some other brand.

The only  pharma companies in india without foreign players' influence are Cipla and sun. Probably they can try.
It's highly unlikely to get approval of some sure-cure drugs like  replicor in US I think. But it's not a big issue to conduct trials here and get approval. But again it's not a simple process.

[LilHope2010]

Nothing is a simple process unless it is handled in the right way....$25,000 may be a huge amount for one HBV carrier but very minute for 3 billion carriers world wide...It is not a bad idea to stimulate a campaign and push the companies to approve the drug in Asian subcontinent....If we succeed in it I can say we are just fast forwarding our struggle to seroconvert in no matter of time...When there is a will there is a way...when we know that something that is going to cure the disease is available we should not waste our time and bang our heads discussing about Immune-modulators or Anti virals....I see so many people desperate to get rid of the disease...I feel it is time to take the steps leading to cure instead of struggling.....After all it is one life,let's strive to make it better by taking better steps and decisions....

[Cjb3695]

Thats crazy, we can get this out to the public easy with the help of these companies with hard facts of results

[4est]

we shall write to this guys (REP9 AC - guys  and Myrcludex-B - guys ) and suggest to put a donate button on the website (e.g. with paypal) and we shall donate all of us. For us main thing is to get well and not to become invertitors, so, we can donate and also we can promo the website on national forums dedicated to hepatitis.

[Cjb3695]

Yea I emailed them questioning why donations are limited to 25k, theres 400million people with hep B. If everyone donated 1 dollar a day, they would be getting more then enough to speed the process up

[4est]

I will write also a email and I think that most of us should write a email to prove that it mater for us. also some emails should to be write to other doctors (e.g. pissa - italiy, hamburg - germany, or france, .... ) so maybe who has some email addresses should posted on this tread.

[stef2011]

we should make a youtube/facebook page with their email address and a standard letter so that even those with bad english can easily send it

after all it is very easy and among all internet forums in all countires they can get at least the money for the trials in india.

to tell you the truth i'd be more than happy to pay myself for my trial like i m doing for gcmaf...they may use the same strategy researchers used for gcmaf

[stef2011]

http://archive.mail-list.com/hbv_research/message/20110808.154606.6d4d4816.en.html

42 million Indians carry Hepatitis B virus: Experts

indian alone can get millions of US dollars just with 1 dollar donation......china has probably even more carriers

[April9903]

I would donate as much as and as often as I can for the cure of this dreaded disease.

[LilHope2010]

Yes we can contact them and ask them to speed up the process.....I think donations from India alone can buy the entire company....ultimately what matters to us is the cure but not some guidelines by ******** organizations like FDA or any....country like USA which is on the verge of bankruptcy has no right to influence drug makers worldwide,its domination will soon become history....as steff said,lets take initiative and spread the message across using twitter, facebook or any other medium....I appreciate stef2011 for his trials and sincere efforts in posting the facts and guiding the community....I think its time to realize and stop shooting in the dark and aim direct to the target....We need not fill our stomachs with nitazoxanides and fill our veins with Interferon Injections when we know that an appropriate drug exists....

[ytdthjznyj]

I would donate too.

[StephenCastlecrag]

Be reasonable guys! REP 9AC is not yet a drug - we don't even know how it is delivered to the body. It is certainly not in a pill form. I believe it is delivered at the moment through infusion. The company is not after donations, it very much likes to be taken over by a big pharma. 25,000 will buy you a share in the company.
If you guys are serious, you should form an association, collect donations, then invest in Replicor. This has been done by other groups with incurable diseases. The investment has risks.

[stef2011]

you should form an association, collect donations....

yes that would be the best option, CFS researcher made the same thing since many governments are trying to hide XMRV virus which is actually more spread than hiv and a real cause of aids.

by the way is rep9ac compound public, if there is apatent it should be?if so any advanced biolab can make it like it happened for gcmaf, especially where there is no patent coverage.if the compound is secret the only way is invest in the company

[stef2011]

what we know for sure is that toxicity of rep9ac is less than current approved drugs

[4est]

you should form an association, collect donations....

yes, that would a good option!

[StephenCastlecrag]

Replicor does have a patent on REP 9AC, but I don't have the details. It is mentioned on their website. Personally, I think an expert can have a pretty good idea of the composition of REP 9AC - 9AC actually tells you a bit.

BTW, I hope you have all heard that scientists have found molecules to block the protein Clathrin that is needed by viruses, such as HBV to enter a cell, i.e., a potential entry inhibitor.

Viral blocking breakthrough

Written by Michael Magnusson | 09 August 2011
Australian researchers have developed a new class of molecules that blocks viruses from entering the body and spreading.

The discovery could lead to new treatments to prevent the spread of bacterial and viral infections, including HIV.

Working in conjunction with German colleagues, researchers at the University of Newcastle and Sydney’s Children's Medical Research Institute successfully tested molecules named ‘pitstops’ effectiveness against HIV and Hepatitis C.

Professor Adam McCluskey said 70 per cent of viruses used a protein called clathrin as a way of entering cells and infecting a body. By inhibiting clathrin’s functions, those viruses had no way of taking hold, he said.

McCluskey said someone diagnosed with an infectious illness could take a drug blocking clathrin, which would stop the illness spreading and the infected cell would then die.

McCluskey said the next step is to refine the compound and conduct more complex animal tests before finally developing it for human use.

[chanthou]

yes, please go ahead and push the drugs that can cure HBV.  Haven't we suffered enough? It's real trauma with this disease.

[Cjb3695]

Yes lets push this, lets first create a facebook with our goals and a twitter to spread the word. Get as many people to like the facebook and follow us on twitter as we go along. Hit as many forums as we can, once we have a huge community then we can start speaking for the community thats backing us and these big organizations are sure to respond!

[vootoodoo]

I've searched for groups on facebook, and found a few with very little participants. It seems to me people are reluctant to talk about such problems in front of all their friends and many prefer not to tell the whole world that they have a desease. In a forum like this one is much easier to share, as there is nothing to hide. There are many of those 400 million that do not even know and  those who do not care. Perhaps we should think how to bring more people here for example and about ways to raise the concerns in those who have no information whatsoever.

[vootoodoo]

I've personally talked to some of my close friends, and not a single one of them had any idea about how HB is transmitted, what it causes etc. Never heard of vaccines as well, or heard, but thought "this will not happen to me". And this when officially in my country about 5% are hbsag+ and perhaps 5% more out of this statistics... I got mine at a dentist...

[LilHope2010]

Yes... I think we should start research about Entry inhibitors, If REP 9AC is not public at least we have a clue where to head... also blocking of clathrin protein seems to be interesting....I find very few chinese HBVers here....China and India are the major nations which would be keen to know about HBV cure... So we should start creating more awareness...

[vootoodoo]

Latest from a friend who wrote to Replicor:

"...We are still making progress with REP 9AC but the drug will not be available on the market for a few years. It takes a lot of time to get all the required studies to be approved.

We are still very enthousiastic about REP 9AC's potential to achieve sustained virologic response in patients with chronic hepatitis B. Our current SVR rate is at 50 %.

The next time we will release data about our clinical trial will be during the AASLD meeting in San Francisco in November 2011"

"Is it possible to say how many years?"

"Probably 3 to 4 years. This is just an estimate...."

[morethenaconqueror2]

The truth is Mycrludex and Replicor are the best options for curing HBV. Due to our NDA I can not release all the details, but I can assure you that both companies are at least 18-36 months away from making market advancements.....However for the scientific mind both drugs can be manufactured in Japan or Switzerland. Your minimum investment would be between 25-50K.
The very best option as a sufferer would be to combine an anti-viral, with short term interferon (to ensure cell turn over) as Mycrludex only blocks reinfection. The interferon would accelerate the cell turnover, the anti-viral will lower HBV-DNA, and the Replicor would promote the HBV anti-body.
The whole process would be less then 6 months.

Would all these companies co-operate on a joint venture NOT likely...Could it be successfully managed as an individual...yes.
Would you need the support of a good chemist...yes
Would your Dr. support you....NOT likely
Would you be cured...yes

[LilHope2010]

Instead of waiting for these companies to release the medicine...we can start our own research on entry release methodology...

[StephenCastlecrag]

Thanks for your comments. Which company is behind Mycrludex?
I like the way you explain certain things: interferon to ensure cell turn over, REP 9AC to promote anti-body.

[raja1972]

German Biotech MYR GmbH develops the viral entry inhibitor Myrcludex

Source: http://www.en.high-tech-gruenderfonds.de/2011/05/high-tech-grunderfonds-invests-in-a-novel-hepatits-b-compound/

[StephenCastlecrag]

Thanks for the link. Good to know Mycludex has moved out of the lab and into a clinical trial.

[chanthou]

What about GS 9620. see this link
http://www.hivandhepatitis.com/2011_conference/easl2011/docs/0412_2010_d.html

Can anyone explain in plain English what this means?

[StephenCastlecrag]

It is a drug that modulates our own immune system to fight the virus. Sorry I am not an expert. Think of it as something like interferon.

[stef2011]

that proves drug makers have all the knowledge to stop hbv but take it out only when they fear cure drugs from small companies.this trl activator came out from nothing, absolutely a prove they hide the cures......

our immune system is complitely blind and can t see hbv and respond to it because macrophages are inactivated.being inactivated mean they dont have active receptors to see pathogens in our case hbv

trl7 is activated by this drug and this is one of the main receptors macrophages (or monocites in general) have to detect hbsag

gcmaf activates macrophages that express all receptors after activation so we should get  a better effect from gcmaf, in any case this drug activates trl7 so that hbsag can be detected by our immune system

i think this drug is not potent enough because to clear hbv we need detection and strong immune responce to hbcag, this response will allow clearance of hbsag complitely.strong antihbs antibodies can develop only after strong hbcab antibodies response.

so i guess gcmaf is better than this drug because it activates all macrophages receptors and maybe it will allow to mount a stronger immune response

as to glead releasing ths drug to market...it will only when tenofovir viread patent will expire in 2015.this drug doesn t look potent enough to clear hbv anyway

[4est]

so until now, we have on the pipeline for the next period the flowing drugs:
- REP9 AC
- Myrcludex-B
- GS 9620

something else ?

[LilHope2010]

I have emailed to Himalaya drug company about Liv.52 HB, they say that the Drug Inhibits Antiviral activity and clears Surface Antigen in most patients....Iam not sure how far it is true...

[4est]

is possible to ask for some more details on Liv.52 Hb (clinical study ...).

I suggest that the rest of us we shall ask on other forums (chines forum or indian forums or ...)  to see if we found some one that use this liv.52 hb and had some results

[Cjb3695]

Interesting stuff, I feel like we need to get everyone in one community, to be able to speak as a whole!

[Cjb3695]

So after emailing Replicor. I recieved an email back today with some awnsers to the questions I asked them.

Here are some brief answers to your questions:

Why arent you guys being supported by hepatitis B organizations that people are donating thousands of dollars too?
They typically do not donate money outside of their countries.

Why are people still using antivirals when we have a possible cure infront of us?
Because our drug is not approved yet.

Why cant us HBV carriers donate money less then 25k to you guys to speed up the process of testing and releasing this drug?
We are looking into this possibility.

When do you think at this rate you guys are moving will this drug be available for the public to possibly get rid of their virus?
We guess at least 3 to 4 years. Could take longer.

Michel Bazinet

[StephenCastlecrag]

2 Therapeutic vaccines from China - both in Phase IIb
1 Therapeutic vaccine from Dynavax
1  Therapeutic vaccine from France
LB80380 - antivral.

[LilHope2010]

http://www.hepb.org/professionals/hbf_drug_watch.htm  
this link contains further details of the future drugs...

[studyforhope]

To understand the true chances of Myrcludex, several factors have to be considered. The sequences of the critical blocking preS1 peptide fragment, myristylated or stearylated, have been published and are available in the paper. Thus the exact  chemistry of the forthcoming drug is known to people who read the scientific literature.

Currently phase one toxicity studies are planned this summer. The next phase , a small proof of concept study with maybe 20 to 40 chronic HBv patients will hopefully start early next year. Myrcludex will be used at the dose of 1mg per subcutaneous injection as shown in the presentation by Locarnini.

Now here is when the problems will start; there is no simple way to see the effectiveness of this entry inhibitor, since the reduction of reinfection is no a measurable parameter,there is no easy test for it. If a patient has rapid turnover - severe hepatitis- a more rapid removal of infected cells can be assumed and here Myrcludex has paradoxically a higher chance to show its effectiveness by slowly reducing the viral load and parallel the surface antigen concentration.

In a low grade inflammation infection turnover half life can be many month and a measurable reduction could take years.

[Cjb3695]

Those Therapeutic vaccine's are sopposed to cure the disease or are they the preventing vaccines?

[StephenCastlecrag]

Therapeutic - means to cure as opposed to preventing. However, results so far from the Chinese trials indicate they don't cure but do lead to seroconversion of the eAg to eAb. The good thing is that  these treatments seem to consist of a series of injection over a finite period.

[StephenCastlecrag]

Thank you for the extra information. I believe Prof Locarnini was speaking at the EASL conference.

I find your comments very interesting. Here is what I think you are saying:

Severe Hepatitis can be the acute hepatitis that occurs when an adult is first infected or it can also be the active hepatitis during the immune clearance phase.
During the immune clearance phase when hbvdna load is high and ALT is high, thus indicating "rapid removal of infected cells". Therefore if Myrcludex can stop re-infection, it may lead a successful clearance.

In the inactive phase, Myrcludex may be not as useful as you say, because during this phase, viral load is usually 0. I think that is why morethenaconqueror2 suggested the use of Interferon to modulate the immune system to kill of the still infected liver cells.

[studyforhope]

Yes, all that  an entry inhibitor like Myrcludex can really do,  is to block the infection of newly formed  uninfected cells replacing cells which have been removed as a result of mostly immune mediated turnover. The speed of clearance in a low grade hepatitis or with patients on antivirals is slow . Thus it might take years to completely clear the liver using an entry inhibitor. Interferon may help to speed things up, but it is not a very popular option .
Additionally in a long term setting at described above, we have to consider the degree of effectivenesss of Myrclurdex. If it is only say 99.99%,  at the chosen dose the infection might still spread back very slowly. Remember that the tupa chimeric-mouse  was treated with 2 mg  per mouse ,which completely prevented an infectious challenge from HBV and HDV as presented at the EASL in Berlin, this is a much much higher dose than intended for humans.

An additional problem with Myrcludex in the human setting could be that anti-peptide antibodies could form which will block its ability to reach the liver and generate unwanted immune complexes .

A further problem is the potential innate immune system stimulation of the lipo-peptide. For this reason myristulation -c14-was chosen  over the Stearyl form  c18.

The cost of Myrcludex is relatively  low in raw materials. About $4,000, while the Replicor treatment will cost $50,000 in raw materials .

[studyforhope]

My previous comment was in reply to Stephen

[StephenCastlecrag]

Many thanks for the expert comments, much appreciated. The cost for Replicor treatment is high, is it because it is difficult to manufacture REP 9AC?

[stef2011]

i guess it is better to try Myrcludex in the immune clearance phase at this point

after your light in to the darkness of Myrcludex way of action i do prefer replicor drug, the only thing i fear is a different effect on hbeag negative since the hbeag guy on the huma trial had no response, do you have any data about this?

i guess hbsag might be produced in different sites on hbeag negative and i guess it is better to combo also on rep9ac to prevent hbsag mutants...what's the best option rep9ac and interferon combo or rep9ac and entecavir/tenofovir/alinia?

[stef2011]

just for comparison 5 years of entecavir are about 50000usd with no effect on virus clearance.....

[4est]

REP 9AC - it is a "surface antigen release inhibitor".
As far as I understood, I'm not a expert, they base on the fact that HBsAg suppress the immune response to HBV infection and they try to supress the release of a HBsAg from the infected liver cells in order to allow our immune system to clear the infection.

Also in this case we face the same problem that @studyforhope notice "there is no simple way to see the effectiveness of this entry inhibitor, since the reduction of reinfection is no a measurable parameter,there is no easy test for it." the time will be longer or shorter base on each immune system.

[4est]

as @steff2011 mentioned it is unknown the efectivnes of REP 9AC on HBe Negative patients.
As far as I read in one clinical trial was only one HBe Negative and this guy don't respond to the tha drug, but this is not enough to have a opinion  (it was only one person, and also some guys on HBe positive also don't response)

[ytdthjznyj]

German biotech firm MYR GmbH (Myrcludex). Contact: [e-mail]

[stef2011]

no rep9ac effect is immediate with hbsag negative and hbsab antibody positive as early as 7 days, that's why i do like this one but it looks like drug makers and fda will make problems for approval so the only way is make the company seek approval in india or china definitely not north america

this drug should be used combo because once the virus looses the coverage of hbsag it is extremely weak to all other drugs

[StephenCastlecrag]

If REP 9AC inhibits release of HBsAg, it should also inhibit release of new virions because they are coated with HBsAg (my guess). This will lead to zero level of HBsAg and hbvdna in the blood - very easy to measure.

Anyhow,in my opinion, we should not have to worry too much about measuring the effectiveness of REP 9AC or Myrcludex, as long as they cure.

[4est]

we wont worry to much about  measuring the effectiveness of REP 9AC or Myrcludex, as long as they cure, but some authorities (e.g. FDA or FDA equivalent in each country) will worry - or at least I think so.

I'm not familiar with the correlation between HBsAg and HBV DNA, I try to read some resarch but I don't see the pattern, so I can't say nothing about this one.

[StephenCastlecrag]

There are drugs that work without scientists know how they work. So the only measure of effectiveness is that they work.

The serum hbvdna is actually the viral dna inside a virion., and the outer coat of the virion is made up of HBsAg. Someone please correct me if I am wrong.

[4est]

maybe will be helpful for all of us to start a new tread and to collect (this information are all over tha posts on this forum) and share the technical information that we have like correlation between HBsAg and HBV DNA, or meaning and correlation of HBe positive / negative, mutation and what this means, pepite ......

[stef2011]

yes you are correct and hbsag is produced in very high numbers, much higher than that needed by virions as coat.this extremely high amount of hbsag is used to neutralize the small numebr of hbsab we have and to block our immune response

when you block hbsag our immune system starts working again, not at full strenght like those with acute hbv but the patern is the same as for acute carriers....alt flares and hbsag seroconversion...once hbsag is negative also hbvdna gets to zero

hbsab antibody is thought to block reinfection of new cells so hbv is cleared by about 6-12 months like in slow acute hbv

[stef2011]

you should check the old posts about rep9ac there is a link where you can see all single patients hbsag, hbsab, hbvdna and alt

they also made a choice of patients with very high hbvdna which is usally cleared easily by entecavir+tenofovir while entecavir only sometimes fails.
it is also good to note that antivirals are extremely slow clearing hbvdna when it is so high, they take 1-2 years if there s no combo

[LilHope2010]

What can we do to make these drugs release in India or China?

[LilHope2010]

Has anyone contact Agency for Science, Technology and Research (A*Star) and National
University of Singapore (NUS) located in Singapore.... We heard they were close to find cure to Hepatitis B in 2009 and no news form them since then...

[studyforhope]

Many thanks for the expert comments, much appreciated. The cost for Replicor treatment is high, is it because it is difficult to manufacture REP 9AC?

The preS1 entry inhibitor (Myrcludex) is used at 1 mg. per day that makes 7 mgs per week ,while, as seen on their poster in Berlin Replicor is used at 400mg per week . The total amount of the polynucleotide AC is such much much higher  and that explains the higher cost of raw material synthesis, which is done with automated column chemistry for peptides as well as polynucleotide's.  Hundreds of chemical steps are involved and it takes days on the column to complete the full molecule.

It is an incredible lucky situation for Myrcludex that it works at such tiny amounts, making it potentially affordable.

As for your question re the blockage of surface antigen affecting (blocking)  virion formation; While a logical thought, this is not the case. The specific blockage  by 9AC  of the isolated surface antigen 20nm particle packaging and release occurs apparentely in the specialized pathway that leads to the production of the surface particle independent from the virion - DAne particle- formation. As they show in the poster, the reduction in surface antigen precedes the reduction in virimea by several month. The viral load reduction is therefore resulting from secondary processes after the surface antigen disappeared from the circulation, most likely either an activation of innate or by reawakening of an adaptive immune response to the epitopes of the surface antigen, which contains plenty of classI  and also class 2 ( helper Tcell)  epitopes , all  conceptually active ( not mutated to inactivity)  and happy to react....But remember it will take time for this adaptive immunity reawakening, siince the vast majority of the epitope specific T cell clones were driven to apoptotic extinction as is necessary for activated T cells to protect the body from chronic overinnflammation. Considering that, the SVR rate of only 50% might be exlained by individual differences in the time frame to rekindle the surface antigen clone production from the thymus and otherwise. A longer time of exposure to AC with a longer chance for this awakening to occur might help to boost the SVR rate.

Never forget that the surface antigen particle concentration is about 10000 times more than the virion, Dane particle, concentration.
While the virus has used the strategy of mutational epitope evasion for core immunity combined with the eantigen for the core, it uses the mass flooding of the system with surface antigen to evade adaptive immunity against the surface Ag epitopes,, BUT DOES NOT MUTATE THEM.. Herein lies the power of the Replicor approach.

[4est]

Thanks for your comments and explanation.
Even if I hardly understand them :), this comments are very much appreciated and help me to understand something from virus and from the way that the researchers try to atac the virus.

You say that "surface antigen particle concentration is about 10000 times more than the virion, Dane particle, concentration." - I that means that Hepatitis B virus DNA is a some correlation with HBsAg ?

How about the actual drugs (antiviral drugs), as far as I know this antivirals work on the vitrion numbers and put this to undetectable (lower then a threshold), but still under this the HBsAg is still present in big quantity. I understood that the pathway for vitrion and is different then the pathway for  HBsAg, but still a correlation exist or ?

Sorry that I'm lost on this and found more questions then answers, so I try to figure out and some supplementary explanation will do good.

[StephenCastlecrag]

I am very grateful for you answer and your corrections of my mistakes. I would appreciate if you can explain to me how REP 9AC act, bearing in mind I am a very amateur reader:

I know the viral dna  is assembled into a nucleocasid in the cytoplasm before combining with the HBsAg into a fully coated virion (Dane particle). I also know HBsAg is produced far in excess to what is needed to coat the virions. HBsAg are also formed into spherical and elongated particles and released into the blood stream.

1.Does REP 9AC block the release of spherical and elongated particles(no viral dna and is non-infectious) of HBsAg from infected liver cells?
2.Does REP 9AC block the release of Dane particles from infected liver cells?
3. Or does REP 9AC block the formation of  Dane particles?

Or am I on the wrong track, again.

Many thanks in advance.

[4est]

from your comment I understand that I looks that I made some confusion between the terms, it seams that I  took the DNA like Dane particle.

[StephenCastlecrag]

I may still be wrong. You see, hepatitis virus's dna should not be able to leak out from the infected liver cells into the blood stream for us to measure. And they cannot count Dane particles in a test-tube (no yet). So I assume they collect the Dane particles in the blood into a test tube, then break down the outer coat and inner core, then measure the amount of viral dna.I try to research on this using Google, I did not get a definitive answer. So I hope some one would correct me if I am wrong.

[LilHope2010]

Another clinical trials by Replicor guys

NASVAC Phase-III Trial in CHB Patients – Bangladesh only
Compare therapeutic efficacy of combo therapeutic vaccine containing HBsAg, HBcAg, later called NASVAC with a commonly used antiviral drug, Peginterferon in CHB patients.  Contact:  Dr. Mamun Mahtab  at [phone]

[LilHope2010]

Its not in Replicor website though... Dr.Mamun Mahtab worked with Replicor team for REP 9AC

[4est]

I have no idea if they are related to Replicor (I don't think so) but below is a link with a presentation of the NASVAC

http://www.who.int/vaccine_research/documents/WNT_Guillen_presentation.pdf

[studyforhope]

Your questions:
1.Does REP 9AC block the release/PRODUCTION/FORMATION of spherical and elongated particles(no viral dna and is non-infectious) of HBsAg from infected liver cells?
YES
2.Does REP 9AC block the release of Dane particles from infected liver cells?
NO
3. Or does REP 9AC block the formation of  Dane particles?
NO

The measurement of viral load is done by extrating DNA from the lysed Dane particles. Since the HBv genome is present once per viron, a Dane particle count can be easily calculated from the DNA amount found in the patient serum.

Surface antigen is produced from the HBV cccDNA (circular, closed coiled) by transcription in the nucleus where the cccDNA resides a a minichromosome. The messenger RNA moves to the cytosol for translation and the surface antigen protein is primarily inserted  (HERE IS THE BLOCK BY REPLICOR) in the endoplasmatic reticulum membrane and later processed into vesicles for export.

Dane particle  HBV DNA is synthesized from the progenomic RNA ( made by transcription from the intranuclear permanent cccDNA) inside partially formed cores inside the cystosol, which close by self assembly to a closed sphere while this happens, causing the partial singlestrandedness (incompleteness) of the second so called HBV genomic  plus strand. The cores are later covered with a surface antigen/membranecoat, that is fastened to the core by inward directed preS1 loops, while the outward, myristylated preS1 loops of the Dane particles are the ones that make later  (after release of the virion from the hepatozyte into the circulation) contact for infection to the targeted  liver cell membrane receptor, causing entry to the hepatozyte. When an artificillay introduced pres1  peptide molecule is already stuck on these receptors (importantly, a small receptor percentage is enough to block!!!) (HERE IS THE BLOCK BY MYRCLUDEX!) then the Dane particle membrane cannot get close enough to the cell membrane to FUSE, thus NO ENTRY, no reinfection, a cleaner liver, day by day....

[ytdthjznyj]

http://clinicaltrials.gov/ct2/show/NCT01374308

[ytdthjznyj]

http://clinicaltrials.gov/ct2/show/NCT00869778?term=chronic+hepatitis+b&rank=27 - there is one more  therapeutic vaccine

[StephenCastlecrag]

Many thanks for that explanation. It corrects many misconceptions I have about the actions of REP 9AC. I saw the diagram regarding entry-inhibition before, in a presentation about REP 9AC and DHBV. I would be grateful if you can indulge me further. Can I say:

1. REP9AC blocks the RELEASE/PRODUCTION/FORMATION of spherical and elongated particles(no viral dna and is non-infectious) of HBsAg from infected liver cells.
AND
2. REP9AC blocks the entry of Dane particles into liver cells.

I have given many wrong information to members of the Chinese Hepatitis B forum. I hope to get it right this time.

Many thanks in advance.

[studyforhope]

NO.  REPLICOR IS NOT AN ENTRY INHIBITOR FOR HBV. IT IS FOR  INFLUENZA, HCV AND HIV, BUT NOT FOR HBV.

[StephenCastlecrag]

Many thanks again! So the duck's model does not apply. Does this mean:

1. REP 9AC is best used with an antiviral (that reduces viral load and thus re-infection)?
2. REP 9AC is best used with an entry inhibitor like Myrcludex?
3. REP 9AC, by reducing the number of HBsAg particles, is sufficient to allow the immune system to do its job in clearing hbv?
4. What is the method used to deliver REP 9AC into the liver cells?

Thanks again in advance.

[stef2011]

thank you very much for all the clear explanation about rep9ac and MYRCLUDEX

to StephenCastlecrag:

just my hipotesis:
what rep9ac can do is lower hbsag and restart some immune response or all the immune response, no direct activity on dane particle at all.....maybe even the gcmaf i am trying can help with this, the first hiv+ guy who started gcmaf about 18weeks ago has got normal nagalase now

my big guess is that once hbsag is negative and hbsab detectable by replicor drug the use of gcmaf and/or interferon might rescue hbv immune response (both cd4 and cd8) and interferon clear remaining infected cells.

[studyforhope]

To Stephen and Stef

1. REP 9AC is best used with an antiviral (that reduces viral load and thus re-infection)?

A difficult question, because a reduction in viral load by the antiviral is also often followed by lower immune activity, that might delay the reawakening of the immune response to the surface antigen after it has been blocked by REp9AC from flooding the system.
Nevertheless, the capacity of HBV to grow back against the reawakened surface epitope Tcell mediated clearance effect should be much weaker with an antiviral in place. HBV is a dynamic disease and the dramatic reduction by antivirals of the replicative capacity of  HBV should help the clearance dynamics.

The blockage of reinfection by antivirals might not be as effective as one might think. The virus overproduces virions tens of thousandfold over the amount needed to fully reinfect. Not only is the UND status misleading insofar as the detection methods still have limited sensitivity and UND could still mean a production of eg 50000 dane particles a day, but yet another critical effect has to be considered. Freshly produced virions in particular will readily infect a neighboring hepatocyte cell from the space of Disse, but also circulating virions will be rapidly absorbed and removed by the liver by its affinity to the preS1myr  binding receptor at the hepatocyte surface. To put it simple, the liver will act like a gigantic affinity absorbing column/mass, removing/ clearing Dane particles from the circulation until it is saturated. Thus even real UND with more sensitive methods might not mean that there is still a large amount of reinfection/remnant virion production  going on.


2. REP 9AC is best used with an entry inhibitor like Myrcludex?
This could be an ideal combination, because any freshly produced or cleared cell will be protected from reinfection, allowing slow but consistent reduction of viral infestation of the liver.
Here is however another critical argument regarding the replacement of immune cleared cells by fresh uninfected hepatocytes; While the mainstream thinking is that hepatocytes are replaced by division from so called satellite cells embedded in the liver ( 'liver stem cells") others think that regular hepatocytes will divide once the regnerative impulse/signal  from Hepatocyte Growth Factor is sensed to replace a shrinking liver mass. The dividing "mother" cell is likely infected, and since there are typically 10 to 30 HBV cccDNA molecules in the nucleus, these will be distributed into the daughter cells, which then, bingo, are already infected from their "birth".
Antivirals typically reduce the amount of cccDNA, but nor dramatically, at best about 10 times.This might still help in this scenario.



3. REP 9AC, by reducing the number of HBsAg particles, is sufficient to allow the immune system to do its job in clearing hbv?

This will depend on the vigor and breath of the anti surface Tcell  (cd8 - cytotoxic/killer as well as cd4 helper Tcells) and later B cell response. It has been tolerized by oversupply with antigen for a long time, most clones will be exhausted or lost. Thus a less than perfect SVR rate can be explained by an insuffcient recovery of that system. It will take time to regenerate, reawake, possibly by the novo supply from the thymus. Some think that the surface antigen mainly acted as a suppressor of innate immunity, that this innate immunity will restart once the mitigating protein hasd disappeared from the circulation. Chisari and the majority of HBV immunology specialist place more emphasis on the adaptive, specific response, since it allows targeted removal of HBV protein producing infected cells. In reality, innate immunity is the danger sensing promotor of adaptive imunity, the two work in intimate collaboration and therefore both need to be quite functional for a successful clearance event.

4. What is the method used to deliver REP 9AC into the liver cells?
From what was  heard at the European meeting, it is by weekly infusion.

[StephenCastlecrag]

Many thanks for the detailed explanations, again. Here are a few more questions, if you don't mind:

1." Antivirals typically reduce the amount of cccDNA, but nor dramatically, at best about 10 times" - This is good news. Is this a recent discovery or well known fact? No antiviral manufacturers seem to state this fact.
2. The liver stem cells, do they get infected too by HBV ?

Finally, how do you see the future of  treatment for chronic HBV? New drugs, new types of interferons, therapeutic vaccines, combination treatments?

Many thanks in advance.

[chanthou]

Dear studyforhope,

I have no clue about virology.  From you have explained, it means Rep9AC is not a medicine for HBV, but for HCV, right?  And it does not much help HBV patients? Our hope may be misled?

Thanks.

[stef2011]

I have no clue about virology......

i think it is better you just consider rep9ac and Myrcludex as we are posting from many months as the first hbv cures without questions because i think there is no easier way to explain

[studyforhope]

To Stephen and Stef

1." Antivirals typically reduce the amount of cccDNA, but nor dramatically, at best about 10 times" - This is good news. Is this a recent discovery or well known fact? No antiviral manufacturers seem to state this fact.

This has been frequently reported at the liver meetings since years now, in poster format.The effect is just not very impressive and reflects the fact that the cccDNA concentration in a single liver cell is dynamically maintained/turned over  at a very very slow rate and that a tiny part of the genomically synthesized DNA does not enter into the virions but recycles to the cccDNa pool thus less produced - by reverse transcription of the genomic RNA - genomic DNA reduces mildly the cccDNA concentration The decrease in cccDNa is reflected somewhat in the surface antigen concentration, since it is transcribed off the cccDNA, but the decrease typically stops at a new equilibrium, very rarely - up to 6% - it leads to surface antigen to Ab seroconversion.

2. The liver stem cells, do they get infected too by HBV ?
The common thinking is NO, the satellite cells are not infectable, probably due to their lack of expression of the critical surface protein receptor gene.

Finally, how do you see the future of  treatment for chronic HBV? New drugs, new types of interferons, therapeutic vaccines, combination treatments?

Therapeutic vaccines have little chance, unless combined with something like replicor, since the antigen flooding prevents any effective immune response to reach the liver. Core epitope vaccines, even particle vaccines, fail, because the core is free of class I epitopes with only one exception the 18 to 27 AA core protein epitope as was used in the classical Cytel vaccine. it failed, because in most chronic carrier of the HLA A2 type, this epitope gets mutated and inactive, so the T cells stimulated/produced by the vaccine target nothing that exists in the virus anymore. This is BTW the only class I epitope that evolution has left in the core protein, against which the virus is normally protected by the e-Antigen flooding, it is also the epitope that is typically responsible for the clearance in acute HBV. It often mutates from one sequence to another when in the eantigen neg carrier an escape mutatnt against its response arises, causing a rise of a new mutant epitope in the high titer virions, followed by a new surge of new cytotoxic Tcells against this mutated epitope, causing severe flares, mostly without final clearance, since now we are looking at a HBV quasispecies at this critical locus.
The surface protein has about 8 class I epitopes of various vigor and affinity, and many more classII epitopes.
Thus core vaccines will produce some class II response of limited effectiveness, leading to temporary increased liver inflammation with a reduction in virion production (reduced viral load) and viral protein expression. But the effect is too unspecific and will rarely lead to clearance and seroconversion. A similar picture applies to the preS type vaccines.

A combination of replicor, Myrcludex and antivirals, with therapeutic vaccines in the surface antigen negative phase to enhance the anti surface response while the surface antigen is still artificially suppressed by  replicor, should drive the SVR rate in the 80 to 90% range. Interferon, possibly more tolerable like lambda Interferon,  might also help dramatically at this stage, but it apparently gets complicated and who would compose or pay  for such a combination therapy?

to Chantou;
Replicor is an entry inhibitor for HCV but has not been tested in humans yet.It is very promising for HBV patients, but the current response SVR rate is only 50% and its currently complicated mode of application and high price for the substance will still pose substantial hurdles for its future development.We all hope it will become available through further improvements in the practicability of its use

[StephenCastlecrag]

I must thank you again. I have been re-posting your posts to the Chinese Hepatitis B forum. I am sure, just like me, they have benefitted greatly from your posts. I am out of questions at the moment, but I hope you will continue to answer our questions in the future.

My very best regards to you.

[stef2011]

let's keep it first page for new members to know

[Cjb3695]

Very interesting and it seems like theres a future to look forward too!

[LilHope2010]

Yes all we are striving to do is to make future become present at the earliest possible time! Join your support to make our voice stronger in this aim to find a cure for the disease

[enolia]

Thanks all for this thread. I am willing like many others here to donate to Replicor or any other form of research support to cure HBV in a timely fashion.
A year ago or so I have asked Replicor DG here in Canada and they sent me the same answer, it will take 3 or 4 years. Right now, they are still in the phase 1 tests.

Too bad that many doctors (including the one who does the follow up for me) are still making bad decisions. The last day, I asked my dr if he was aware about any place in Canada where I could get my HBSAg count done, he said no and he wasn't aware that this was an important factor to cure with Interferon. He said he prescribes interferon to ''motivated people'' without checking their HBsAg or even their genotype!! I was thinking: Oh my god! Poor hopeful people who wish to get cured with interferon and get all these horrible side effects :((

Really it is not acceptable that doctors are still ignorant of all new researches and updates in the HBV domain...

[LilHope2010]

Thanks for your concern enolia... If you live in Canada or nearby probably you will have the best chance to follow the developments of Replicor...If possible try contacting Replicor guys and let them know about our funding plans...

[enolia]

I can contact them for sure but do we have a plan? :)
Who is participating, etc?

[vijik]

Hi.
We already have had lot of discussions about funding to replicor in this thread itself. Try to contact them and let stefano or stephencastlecrag know. As of now we don't have the right person to contact replicor. Probably you can do this. And please try to find out the funding methods in Canada. Shall we form a trust or foundation? Which one is the simple way to get money to Canada from all over the world.
Thanks.  

[LilHope2010]

Once the company is ready to receive funds and assures to speed up the process of releasing the medicine into the market...We can accumulate in no time to contribute the money to the company..

[enolia]

I will contact them and ask about the best funding method and let everybody know.

[4est]

Hi studyforhope,

First, thank you for your detailed explanation and I wnat to ask you if you have some information that can be expose also for GS 9620.

[enolia]

I thought I would post the 2011 EASL REP 9AC presentation link

http://www1.easl.eu/easl2011/program/Orals/339.htm

It looks very promising.

[LilHope2010]

Seriously its very good information....People are struggling years to seroconvert, REP (AC cures hepatitis B in just one week,unbelievable....I look forward for the release of the medicine asap

[enolia]

I just had an answer from Replicor, I will discuss the funding issue over the phone on Monday with the CEO. I will let you know!

Enolia.

[vijik]

Wow. With CEO? Great work. Try to let him know about this entry inhibitor thread. He ll try to understand our spirit.
Thank you.

[enolia]

Ok, I will send him the link. He said he will call on Monday, he is busy today and tomorrow.
IF you check on their website on the link below and click on the investors link, it is the CEO who takes care of any investments. Don't forget it is a young company so it is still easy to speak with them :)

http://www.replicor.com/debut_anglais2.htm

[vijik]

ok. I check it out. Thank you.

[vootoodoo]

Does anyone have a contact with the forum administrators who can provide some sort of  statistics about how many visits this thread receives, in order to know how far the word can go by this means.

[LilHope2010]

May be steff can help regarding it.... I have found many other communities just like ours over the net...May be we should start trying to link up with them including the Chinese community and start spreading our voice

[ytdthjznyj]

  I'm ready to  start spreading our voice in  Russia.

[vootoodoo]

I will translate this and some other threads from here and post on the Bulgarian forums

[StephenCastlecrag]

The American Hep B group can be contacted through their website:
www.hblist.org
They have about 5,000 registered members and is the oldest Hepatitis group with the best archive of research articles on Hepatitis B.
The Chinese Forum with over 470,000 members can be contacted at:
www.hbvhbv.com
You will need the service of language translation software to view the site. Or contact through me.

Stephen

[nimrodken]

We need to work hard in showing this in the web so they can hear us  and somehow help us with this disease.

[vootoodoo]

Well, then get to work :)

[judas13]

   GO! GO! GO! WE SUPPORT.....!!!!!!!!!!!

[enolia]

Ok, I got some info:

Replicor CAN NOT put any Donations link on their website because they are not a non-profit organization, they can not take any money from normal people. Though they are very excited about REP 9AC and to help people around the world. I believe there should be some other ways to support them...We will discuss more. Any ideas, let me know and if you would like I would suggest to them.

[LilHope2010]

If they are not ready to take donations we can make them to sell shares in the stock market....All they have to do is to release an IPO, both the company and people who will buy the shares will be benefited here and it is strictly legal process so no hassles

[LilHope2010]

By their website I learn that Replicor is already accepting investments from the private investors....



REPLICor is a private Canadian company based in Montreal. Most of our shareholders are private individuals and companies that share our vision of creating a drug that has the potential to revolutionize the treatment of patients with chronic hepatitis. This drug is now in the human trial phase. In addition, this same drug has been shown in vitro and in vivo to be effective against a wide spectrum of other important viral infections.



REPLICor was nominated as one of Canada’s Top 10 Life Sciences Companies for the years 2004/2005 and for 2007/2008 by the Ottawa Centre for Research and Innovation.



See: http://www.topcanadiancompanies.ca/winners/alumni.pdf



Periodically REPLICor seeks new investment funds. If you have an interest in becoming a shareholder please contact the Company for additional information.



Michel Bazinet, MD

Chairman of the Board and CEO

***@****

Tel.: [phone]

[enolia]

I like the idea of buying shares in the stock market. Very smart!
I hope they like the idea...

[StephenCastlecrag]

Replicor is not yet publicly listed on any stock exchange. Buying shares in in a listed Replicor is the ideal way to support the company, but It costs money to issue an IPO.
In seeking private investments, Replicor follows strict rules, one of which is the minimum sum of investment.
Hope I got it right.

[LilHope2010]

Yeah may be its not listed but still Replicor is accepting investments which is minimum sum, may be we (HBVers) can form an association to accumulate that amount and provide it to the company as a share.But since this community has members world wide it is a challenging task to make a strong point and bring everyone on one stand, It is important for us to create a strong base first, then members will throng automatically....Before planning all this some of us should communicate with Replicor and know how are they going to respond with our idea...Its not a big deal for them to go public and release an IPO if they learn that large number of people are gonna support/donate money to them, mean while I request all the members who read this thread to share this idea with as many people possible worldwide....We never know when and how miracles happen

[4est]

IPO are good and not - this can be very dangerous because of the fluctuation and also because of the possibility to lose the company management ... a big player will easily balance and maybe turnover some of the investment from HBV people. - all above are my supposition (and maybe aren't corect).
I don't know details of IPO but I thinck that some security measure have to be taken. Meanwhile I think that a good organization for HBV patients will be in a national groups and all this groups to have a people in a international group - Easy to say hard to do especially because we are discussing a lot of people and also money are involved, but it worth a chance.

Proposal: list on this tread or in another thread all organisation / forums / ... from your country and if is possible the number of members.

[stef2011]

i think the big problem is just to find a very trustable subject to open a pay pal account of whatsoever to collect money and then give to replicor if amount or when amount reaches the minimum.

i am no expert at all on finacial issues so all this maybe fantasy but....is there a legal way tht a single subject receives all the money and then give to replicor but laws that make possible to donate this money only to replicor (this single subject cannot take the money and also the money cant be taxed because donations)

[4est]

I'm not a finance expert also, but my proposal, the one to have a national organisation for each country was made in order to allow to people to follow the law in each country.

I will have a look into this in more details during next week and if I found something more, I will came back with new information.

[enolia]

Stef, what do you mean by finding a very trustable subject to open a paypal account?

[enolia]

Do you think of having many branches of Replicor in many countries so that people can invest in their own branch?

[vootoodoo]

Has anyone tried to reach the Bill Gates foundation? After all that's what they do, and at least can give some advice.

[4est]

Do you think of having many branches of Replicor in many countries so that people can invest in their own branch?

No, Replicor have to have only one branch (many only if it is required by the operation).

I refer to national organisations of HBV people, non-profit organisation / foundations, and this organisation / foundations can collect money form the people that want to donate, can give documents back if needed ....
In the end this money have to reach Replicor and I was thinking that all national organisation have to made a international organisation and this international organisation to invest or donate or found a way to pass the money to Replicor without braking any law.

I second stef2011 idea - that the best way is that this accounts to be on paypall and to be transparent to all people that donate.

for the moment all this are only ideas and if somebody has some other ideas please post all ideas in this post to be discussed and criticsed by other members.

[enolia]

I was looking online and it seems like there is a way to set a non-profit account into Paypal and accept donations through Facebook.

http://softduit.com/how-to-set-up-paypal-for-a-non-profit-accept-donations-via-facebook/

During the process, you have to prove that you are a non-profit and depending on your donations monthly amount, you pay specific transaction fees %

[enolia]

I did some research online and there are already international no profit organizations for hepatitis:  Hepatitis foundation international: http://www.hepfi.org/ or Hepatitis B foundation, etc. but they seem to be playing more of a social role (informing essentially)...Not at all involved in seeking or supporting cures or pharma companies...I believe that the best thing is for all of us, HBV patients, to become shareholders or somehow influence our governments to support these pharma companies because for example in China alone nearly 500 000 Chinese Die of Hepatitis B complications each year. It is terrible, action is needed now.

[4est]

you are right, exist hundreds of nonprofit organisation all over the globe, and each country has one or more of this organisation, but I don't found any organisation that is focus to new drugs development, most of this are focus on social parts and on prevention.

To influence governments or big foundation is easy to say and hard to execute, we need a name and some achivments before we can go in this direction - this is my opinion, so to become shareholders is more realistic from my point of view.

as the paypal account is a good option, but I will avoid facebook, some time ago I had a look on facebook for support groups or for other groups related to hepatitis and I found very small number of people on this groups. some how the people with HBV are try to keep this only for themselves and maybe family, and also society don't have a good look on the people that have HBV (especially in asia as far as I read). so, for this reasons I will avoit facebook, or let say not base on facebook and i just try to found a way to assure people abut the privacy.

[stef2011]

i'd definitely focus the attention to our group here in medhelp, i have to say i have never found a similar group on the internet as updated info, researchers and real kind people (something closer to this is chinese forum but not exactly like medhelp).

i am always very grateful to HR "hepatitis researchers" for his warning on the dangers of lamivudine and adefovir and the many lives saved by this info.steven NY and cajim who kept discussion and kept waring since obviously HR can t post here often

even if i have been lucky having international researchers at home it is always good to have the same info confirmed here, or new info they are not aware of.....especially all the info on nutraceutical antifibrotics that could regress my cirrhosis in just 1,5years to almost no fibrosis or irrilevant fibrosis(6kpa)

since "all this great info and the truly warmth" is all registered here, i think we just need to link this community anywhere and show the world we can do "the difference", it is years of posts and info all very updated, sometimes even earlier than conferences, all this means you can trust medhelp community and join our cause for "real hbv cures now" with no worries of doing the wrong thing

[enolia]

True...Unfortunately people don't like to share their HBV with their friends on Facebook, that is why hepatitis B on Facebook has very little number of people

[enolia]

...And Facebook like Celine Dion's has over 5 million fans...

[stef2011]

i think that in facebook they obviously dont make friends with the group (i hate facebook too for the privacy outbreak) but i am sure they read, especially if there is something about "cure", once we link here they read and probably become members here with anoher name without any privacy outbreak

i'd use facebook, twitter but especially google, i notice our medhelp group appears easily on google results thanks to the many discussions.google is the first place they look for, the second might be youtube and the las ones facebook or titwer

[4est]

to link all people in this is a good idea, but what about the one that are not good in reading / writing in English and I think that are a lot.we have to found a way tor translate and pass all information in a way that is simple to understand for all of us (e.g. maybe to translate esential information or .... ).

[stef2011]

or directly link google translations, lthough i dont know how long the translated links last

[4est]

Interesting presentation and some technical details forMyrcludex-B  and other drugs actions:
http://www.ihlpress.com/pdf%20files/resistance10_presentations/02_Locarnini.pdf

[LilHope2010]

How about letting press and media know our thoughts about HepB cure in this community.... There are many news websites and channels today worldwide...Im sure a right spark will ignite the news, It would help us without affecting our privacy

[enolia]

I thought of that too but first, we need to work on building a big community to support our idea then involve media to make our voice heard, especially if we are talking about supporting a specific pharma company or product...

[vootoodoo]

Found that about patent application by Replicor in India in 2005 and 2007. Just single articles, and, strangely, published in 2010 and 2011 respectively. Nothing more mentioned anywhere else. Is there a way to check the status of those patents/applications and if they actually exist??

http://www.allbusiness.com/medicine-health/diseases-disorders-infectious-disease/15946855-1.html

http://www.allbusiness.com/medicine-health/diseases-disorders-infectious-disease/16385638-1.html

[chanthou]

Has anyone heard of Zadaxin.  Here they claim it can treat HBV and is approved in many countires:

http://www.sciclone.com/?page_id=900

[LilHope2010]

Yeah Zadaxin is another drug which is in phase 3 trials....BUT is useful to treat HBV but not to 'cure' it.... Remember so far only REP 9AC and Myrcludex-b have data that shows a cure for Hepatitis B

[StephenCastlecrag]

Zadaxin is FDA approved orphan drug for the treatment of liver cancer. Used by some doctors in China to treat HBV, but not elsewhere.

[chanthou]

How is it?  Can it control HBV like Tenofovir or Entecavir?

[StephenCastlecrag]

Zadaxin is an Immune stimulator (whatever that means).
Tenofovir and Entecavir inhibit the production of new HBV virions inside the infected liver cells. Therefore they will reduce serum hbvdna. Some how as hbvdna decreases, ALT also normalizes, but cccDNA is not affected, nor the production and release of HBsAg coated particles(non-infectious) inside the infected liver cells.
Hope I got it right.

[4est]

Zadaxin can be considered like a Interferon?

I saw that this Zadaxin is a old drug (2000), do you have any results on Hep B from Chinese forums ?

[chanthou]

Since we cannot find a cure at the moment, if Zadaxin can act like interferon and is as effective as Tenofovir, I think we have another option pending a cure.  The problem now is resistance occurs with Tenofovir, HBVers will die because we have no treatment option. I wish Zadaxin to be able to bridge the gap between current treatment and the cure in the future.

[4est]

Entecavir has a 1.2% resistant after 5 year (virus have to made 3 mutation in order to develop a entecavir resistance) but Tenofovir has no resistance until now, as far as I know.

Anyway Zadaxin is a old drug (has around 11 years ) and I don't think that the has a very result bemuse we will found out until now, but who know maybe is new in hep b tx.

but let jut wait, maybe StephenCastlecrag or stef2011 that are seniors know more about it.

[stef2011]

we said already many times, and you keep posting like spaming, the only hbv cures are rep9ac from replicor and Myrcludex-b

why do you keep spaming with zadaxin, tenofovir, interferon...we always said on this community they are not hbv cure and they are not registered as hbv cures and they have no effect on hbv!are you a drug maker?

[stef2011]

for all not aware, zadaxin os totally useless for hbv, it cannot even have any effect on hbvdna and it is around before 2000 with poor trials.

it is wasted money and useless on both cancer and hbv.cancer can be cured by gcmaf and hbv by replicor and Myrcludex-b

i wont report these posts but please stop spaming about zadaxin, it was also sed in italy by my doctors/researchers and their trials were the most well designed, totally useless drug

[focault]

After reading all the comments I must confess that just the thought that a cure exists NOW and its delayed/kept in the drawer based on someone's logic on ROI/profits logic gives me chills more than the HBV itself. I am not naive but we are talking about HUNDREDS of millions of chronically ill people. Millions of them will be experiencing pain/death/misery in 5 years timespan. Just imagine someone (hypothetically) knowing this and thinking "neah ... its not enough profitable now ... lets delay it a bit because ...". I think I prefer to have HBV than to be in the shoes of that individual. Many times I prefer to think its just difficulties related to finding the cure (technical, financial etc.). Am I too optimistic to believe its just a matter of time until cure is found ?

[stef2011]

i was like that years ago thinking that profit could never go so bad but after i started to know researchers and studying the horrible truth went so clear, just check our gcmaf threads...gcmaf is a cancer cure and cured 100% of people in the small trials....it is not patentable because a blood substnce like platlets and so on and was studies first by US army in the 50-60's
do you see this cancer cure around?only european countries have it now thanks god but only the most advanced oncologists and researchers are aware or people that find this by chance here on internet

swine flu and hiv is even more ridicolous, check out the documentary house of numbers

[stef2011]

the cures are already all there mostly but only profitable ones (cronic (chronic) cures) are out.things that cure definitively are not profitable enough so for all diseases is like this replicor situation

[focault]

How is it possible that stupidities like those games on Facebook can fund themselves from millions of subscribers, yet when it comes to death or life Replicor cannot accept donations, funds etc.(unless > 25 k$) ? It borders on absurd that so many chronic HBV patients worldwide cannot find a way to channel some money towards this small company that can be the Holy Grail of this dreaded disease. If I would be the government of China I would just relocate them to China and give them some hundreds of millions to finish their work if the West is so self-centered in profits. I am not saying China is an ideal place but HBV is so endemic there that it would clearly bring immense benefit to them. Sorry for my anger but I am reading about Replicor since 2-3 years already now and while I know research is hard and expensive just the thought that in addition to that you could have obstacles lig big pharmas pisses me off to no extent. Look at this forum and what people can do together: it is an invaluable knowledge base. Can't we find a way to accelerate the Replicor development ? So WikiLeaks can get donations and Replicor not ? It is straight from Kafka ...

[4est]

your angry is justified and shared by many people from this forum and also from others.

Can't we find a way to accelerate the Replicor development ?
This is what we try to achieve on this discussion , to found a way to go and help Replicor to continue and speed up the research. so if you have some ideas, fell free :)

So WikiLeaks can get donations and Replicor not ?
Unfortunately also the research company have to respect some law and Canadian law say that a company is not allow to receive direct donation and because Replicor is not a public company the minimum investment  is establish by the guverment. To change the rules from politically point of view  is a long and hard task (almost impossible), so is better to focus on some idea to deal with the current low and found the best way to achieve our goals.

[stef2011]

http://www.replicor.com/debut_anglais2.htm

This drug is even the first broad-spectrum antiviral compound ever described having activity in at least 12 families of viruses......some of these hcv, hiv,influenza, Human metapneumovirus, Respiratory syncytial (RSV), herpes viruses, Cytomegalovirus (CMV), Varicella zoster (VZV),Epstein-Barr (EBV),  Human herpes HHV-6A and 6B, Friend leukemia, Ebola,Marburg,Lassa fever,   Vaccinia (smallpox surrogate), Mousepox (ectromelia), Hantavirus, West Nile, Yellow fever,Dengue and probably more......

ALL THESE VIRUSES HAVE NO TREATMENT!WHAT DO WE NEED A TERRORIST ATTAK TO HAVE A DRUG ON THESE INFECTIONS?

as focault said we are terribly controlled and made o stupid to waste money on the most irrielevnt things or even deleterious and medicl community even keep things like this hidden from public.i think media control is something real at this point and maybe only internet has some freedom left

[focault]

Then Canada's law is crap in this particular case and they should move out their HQ somewhere where they can receive funding properly.These people from Replicor (Michel Bazinet and Andrew Vaillant) are extraordinary scientists and I am sure they have the best intentions. To potentially save hundreds of millions of people is no easy feat in someone's life (I am old enough and never saved anybody from death). These are the true examples of humanity to look up to. Their contribution could be enormous (same level to Einstein or Bohr or Newton). Eradicating this diabolical cccDNA machine from the face of the Earth is as big as walking on the moon. Bigger than defeating the nazis. Does anybody realize what would truly mean to eradicate all these incurable diseases that stef2011 listed above ? All potential victims of all world wars are nothing as a number compared to how many are infected with HBV DNA (not even mentioning the rest of the diseases curable by Replicor). Screw politics. Politics never really solved anything. Science and engineering did. I think I might appear stupid by these comments but sometimes I just have to shout it all out. I am not naive, nor optimistic, i know how the world works and yet it seems all the obstacles are of the most idiotic nature (stupid laws, profit considerations or obtuse governments). I really think that if tomorrow humanity would find out that its about to be hit by an asteroid, politicians would be very busy discussing if its legal or "economically feasible" to deflect it :/ Damn it.

[vijik]

Well said. Appreciate your comments. Until US file bankruptcy you ll never get any good things that cure you. It's the right time to do something when they are struggling to find a solution to fix their already deteriorated economy by bringing down the expenses.
If you notice, they are the **** who introduced people the all worst economic system called spending story or what ****. By the so called spending economy they make their own people insolvent.
Wherever their government enters the problems starts. And the problems they create are chronic.. Never get a solution. Just see Japan,Iran,Korea, etc.,. Of course we, the hbvers, are also victim of their grave crave for money.

[vijik]

Well said. Appreciate your comments. Until US file bankruptcy you ll never get any good things that cure you. It's the right time to do something when they are struggling to find a solution to fix their already deteriorated economy by bringing down the expenses.
If you notice, they are the **** who introduced people the all worst economic system called spending story or what ****. By the so called spending economy they make their own people insolvent.
Wherever their government enters the problems starts. And the problems they create are chronic.. Never get a solution. Just see Japan,Iran,Korea, etc.,. Of course we, the hbvers, are also victim of their grave crave for money.

[enolia]

There is something called The FDA Fast Track Development Program is a designation of the United States Food and Drug Administration (FDA) that accelerates the approval of investigational new drugs undergoing clinical trials. Such status is often given to agents that show promise in treating serious, life-threatening medical conditions for which no other drug either exists or works as well. This is the wiki definition of the program. Assuming this is correct, I wonder if Replicor applied for such a program and how long/money would it take for them to get enrolled and finish their trials?
If nobody knows, I will ask them directly. They are currently busy doing their clinical trials in Asia but I can ask hoping for an answer soon.

[stef2011]

fda lately blocked vitamin c trials for cancer......they said it was never registered as a drug so it can t be used on cancer!

they are also saying that everything injected must be a drug, even a vitamin

can you even dare to think anything that can be less ridiculous than this?this people just needs to be cancelled from the world because they are just the durgs makers market entrance control, paid by drug makers to exsist and nothing to do with patients or healthcare

[stef2011]

they will never approve things like replicor's drug, gcmaf or anything making damage to US market

[chanthou]

I'm a poor person, not a drug maker.  All I need is to save my family. I just want to ask if anyone know something hopeful about Zadaxin.  I am even waiting to hear from you about your experience about Alinia, but I hear nothing. We are taking Tenofovir while waiting for another drug if some day Tenofovir does not work.  We imagine what will happen to us if Tenfovir, a supposed to be the last drug for HBV at the moment, cease to work and the virus flares up.  I don't care Replicor, Murcludex or anything as long as at least we have a back-up for Tenofovir failure, it cure cannot be found in the near future.

Our fear push us to think about any possibilities.  That is why I join this forum.

[focault]

Well, I think its pretty clear that Tenofovir is top of the line currently. Zadaxin is not (its old and as stef2011 said proven to be much much weaker). I understand your anxiety but if, as you said, Tenof. stops working I am pretty sure that Gilead will arrive just in time with another "***vir" more powerful than Tenofovir while still not curing this crap of a disease. Now, seriously stop worrying about Zadaxin. Nobody knows because probably is far below the bar set by Entecavir or Baraclude. If the assumptions about how things work in this world are correct then about the time Tenofovir shows any resistance then we will get another useless nuc that does not cure but lowers HBV DNA. Stop worrying and start living. HBV is serious but many of us managed to live long and productive lives. I'll be damn if I sell my skin so easily to this disease. You hang in there. What you find on this forum is information not cures. Information is power over this disease. And you should appreciate the fact that people gave you some information about Zadaxin and their point is you should avoid it (if you can) because it is weak. That is valuable information in my opinion. Use it wisely.

[stef2011]

tenofovir is likly to make no resistance ever infact drug makers tried to delay its use as much as possible but likly european fda approved it in 2008 so US fda had to do the same in 2009/2010

we have to care for an hbv cure only, as  focault said industry has already many many drugs like tenofovir.all hiv drugs are probably active on hbv so we have 5-10 other nucs to use even without introducing new ones

[StephenCastlecrag]

Zadaxin is used by some doctors in China, but it is not in their Guideline as a standard treatment. The most generous comment I hear is that: "you can use it if you can afford it."  Zadaxin is not used in Australia for Hepatitis B. There are a lot of unscrupulous doctors in China and many patients are desperate enough to try anything.
Personally, I will not advise the use of Zadaxin.

[StephenCastlecrag]

Tenofovir has no reported cases of resistance so far. I heard someone said that Truvada (Tenofovir/emtricitabine) is the backup if resistance for Tenofovir is developed. Truvada is approved for HIV, also manufactured by Gilead. I am not sure if the statement is correct. Stef2011 should be able to tell us more.

[4est]

thanks for your clarification. - It is like we all assume, not a standard therapy and the results are poor.
Unfortunately, some unscrupulous doctors exist all over the globe and this is why patients have to stay update on the latest news and research results. On the other hand we have also good researchers and good doctors and I want to believe that they are more numerous the the other.

[stef2011]

tenofovir+lamividine would be the best combo from the start because truvada (tenofovir+ftc) has some heavier sides on kidneys and ftc is similar to lamivudine.....but this is all useless discussion since tenofovir has no resistance

there is a new type of tenofovir ready with improved halflife, it is nothing new but drug makers make it look like a new drug......less resistance and no kidneys toxicity, i believe it is ready for the market after 2014-2017 when patents expire.potency is some folds higher than tenofovir

it is just tenofovir but transported by other substances like liposoms or similar

[stef2011]

anyway let's try to stay on topic, even if chantou is not a spamer she is making discussion off topic acting as a spamer, i already told her to stop and open new posts instead of going off topic

so it doesn t matter what she is, she must stop posting off topic here

[enolia]

What if we use social networks + Media to make Rep 9AC benefit from the fast-track status since HBV is a life threatening disease for so many millions? Hoping that this would put the pressure on the FDA...?
If this doe't work, it would at least affect the FDA reputation in the world.

[raja1972]

the biggest problem to put pressure on FDA is the lack of numbers thru social network/media as people don't want to expose their idendity..otherway is to take this issue to FDA through representations from HBV associations but i believe this will not happen as most of the associations are funded by drugmakers.  any alternative approach??

[stef2011]

develop drug in india or china, i dont know if you have noticed but when entecavir and tenofovir has come to market development of all nucs has been blocked until the patent expire so even nucs are now being developped in china

with the current crisis there is nothing to expect from FDA, they even invented the swine flu to make money when the US crisis was exploding.in europe there was even a legal trial against people involved in this fraud but as usual they wil find a wy to silence this, european media has already stopped talking about it

[LilHope2010]

Below are some of the website links belonging to Hepatitis B websites and Communities worldwide...I kindly request the forum members to visit these sites in their free time and mail them about our concern and discussion....Based on the response we will start knocking the doors of media...Some one asked why is Wiki-leaks getting funds but not Replicor...The answer is this is a deaf world and we need a bang to make the deaf world hear us!! That is what Wiki-leaks has done!!

All the best

http://www.hepbwa.org/what
www.hepb.org
www.hbvadvocate.org
www.hepatitisbannual.org/
hepatitis.med.nyu.edu
www.ceh.org.au
www.hepbinitiative.org
www.hepfi.org
hepprograms.org/apia/
www.medpedia.com/communities/276-Hepatitis-B
www.cancercouncil.com.au/bpositive
www.calhep.org
alliance.hepatitis.org.au

[enolia]

This Facebook page is called Fight the FDA. I thought I would share the link :)

https://www.facebook.com/group.php?gid=2300333797

We are not the only ones unhappy with the FDA.

[4est]

unfortunately "This group is scheduled to be archived"

I believe that the power is in our hands and not in other hands, we should look on the ways to fight for our believe and not to join some others believes or groups

[enolia]

I believe it is a maintenance Facebook activity. Facebook will be archiving all groups created using the old groups format. When this group is archived, its wall posts, photos and discussion threads will move to the new groups format, but group members will need to be re-added.

Any external support is good at this point.

[focault]

I quote from Wikipedia's article regarding Jonas Salk (inventor of polio virus vaccine):

"When news of the vaccine's success was made public on April 12, 1955, Salk was hailed as a "miracle worker", and the day "almost became a national holiday." His sole focus had been to develop a safe and effective vaccine as rapidly as possible, with no interest in personal profit. When he was asked in a televised interview who owned the patent to the vaccine, Salk replied: "There is no patent. Could you patent the sun ?"
To put it in perspective what polio was: "Apart from the atomic bomb, America's greatest fear was polio."

Where is this spirit gone ?

Today, Replicor could be many times over what polio vaccine was (due to how many diseases it addresses therapeutically) and yet its somehow very difficult to accelerate development. Spending a few trillions on few dumb wars is perfectly fine and Congress approved all of them, yet we, the people, cannot donate 1$ to Replicor because you see ... "there is rules" and big pharma cannot possible jeopardize few billions more from "XXXvir" and "YYYvudine".

Are these guys from Replicor aware of the dimension of their cure ? If 10% of the 350 millions HBV chronics would donate 1$ ... imagine that ! or 10 $ ...

Or may be Roche or Gilead or Glaxo also have even bigger "imagination" on the account of Replicor :/ ... I can bet on that ...

[April9903]

I am from south east asia, have a simple life and I do not know how the phama corporations work, until I join this forum. I gain so much valuable knowledge and helpful advice from the members of this forum who are so kind and helpful to total strangers, I thank you All for this.

Yesterday I watched the movie called " Capitalism : A Love Story " by Michael Moore in HBO and I was horrified. It is so unbelievable and now I know how the world works in USA; it is truly very unpleasant. Does anybody know this movie? I just have the idea that Michael Moore could be the person who can tell the world about all the viruses and how the drug makers are blocking the cures of all those diseases and so on. He could be the media to let the world know that there are cures like gcmaf for cancers, REP9AC and Myrcludex-b for hep b,c ,hiv, and so on. He can talk about FDA issues and many others. He is approachable through his web site and I am sure he has the good story with us and we have the media with good presentation and facts. This is just an idea that I share with you.

Please check his web site and if you see this movie you will know what I am talking about. Michael Moore is the Acadamy Award winning film-maker and author.

[stef2011]

i suggest you see also "the house of numbers" documentary, HIV is and its tight connction to aids with all the false positive tests results is also a fraud...from the words of luc montagner:

http://wn.com/Nobel_Laureate_Montagnier_HIV_Can_Be_Cleared_Naturally__House_of_Numbers

[stef2011]

yes it would be great to show some film maker how we struggle for the cure, an even a short documentary to post on you tube would help....and since rep9ac ia a broad spectrum antivirl i'd put all those viruses together with hbv to the attention of people so the focus is not "hbv cure only" but the pharma industry blocking a universal antiviral that could save us from hbv, hcv, deadly influenza strains or simply a terrorist attak with viral bioweapons

[StephenCastlecrag]

I want to correct my comment concerning Truvada. According to Professor Anna Lok,
Entecavir is the preferred treatment for patients with Tenofovir resistance. Truvada may be used as a rescue therapy for patients with lamivudine, telbivudine, adefovir or entecavir resistance.

[4est]

should we understand that also Tenofovir has reported some resistance or the rescue therapy  was a determined by a theoretical model ?

[focault]

I might be wrong but I think the issue of tenof. "resistance" is more encountered in cases where in fact tenof. is less efficient because of an already existing resistance to something else (lamivudine or adefovir etc.). I did not find any info about tenof. resistance in treatment naive patients (naive = never took any kind of nucs before). Until now tenof. at 5 years has virtually 0% resistance. Somebody correct me if I am wrong.

[stef2011]

just want to remind that we are going off topic gain

tenofovir resistance for hbv doesnt exsist, there is people using it about 12years now with no resistnce (started about year 2000 when approved).even reduced potency mutants in vitro respond to the drug in vivo

this is because the drug has different kinetic/half life (i dont know the correct words, read this a lot of time ago), so that the virus can t develop resistance to the drug.

even partial responders with detactable hbvdna for years have no mutants.......and even if we get a mutant i posted earlier we have a new version with (dont remeber correct numbers but it is about that):

300-350 fold more potency on hiv and activity on hiv even after having developped hiv mutants that dont respond to normal tenofovir, so maybe a drug to overcome resistance issue on hiv

something like 5-10 fold more potency on hbv, so definitely no way for hbv

this tenofovir with new compund to transport in the cells resolve also kidneys toxicity

so definitely tenofovir has no resistance for hbv and we dont need to be worried about this at all

[focault]

Add on: I think that talking about resistance is significant in term of probabilities. Anything is possible in this world. Probablythere are cases where people develop resistance to tenof. (due to particular mutations, cross-resistance with other drugs etc.). But data until now points that they are very very rare when compared to other nucs. Lets not deal  in terms of absolutes because all discussions regarding HBV DNA are possible only when dealing in probabilities (until a true cure arrives). In terms of probabilities, tenof. has a verry good resistance profile compared to others.

[4est]

thanks!
@ stef2011 you are right, we are off topic, so all of us should keep this discussion on topic and start new topics if some other question come out.

[joc2011]

Any update on  when these entry inhibitors will become available- REP9 AC and Myrcludex-B? Lets keep our focus on this discussion!!!!

[vootoodoo]

If there are any Bulgarians reading this forum, please be aware that a week ago I started a thread in a Bulgarian forum ( http://forum.********.com/ ) dealing with hepatitis issues. I was posting info about the new medicines, trials and tests that are being discussed here. And then all of a sudden my account was suspended without explanation!!! So make your own conclusions what kind of help you can expect there...

[stef2011]

there are many fake websites made by drug makers, "the body" is one of the main drug makers  hidden advertising for hiv....the very good part is there is no discussion just you asking and somebody (supposed to be a doctor) answering

another one is "hivandhepatitis", they even hidden new experimental drugs on hbv..they once had a chart which is now totally empty.

i send emails about replicors to almost all these hepatitis associations a couple of years ago and nobody answered.....

[enolia]

It is frightening when you imagine how those people think, just about $$$$$$...OMG

[Izzy79]

In wich of the two bulgarian forums have you posted? May be you should contact one ot the moderators.You can write me a private message if you want!