gilead trl7 agonist and others already marketed

[stef2011]

i was checking for trl7 agonists and i found there are already 2 and one marketed already and even generic, they are used on viral infections to activate immune response on HPV, herpes viruses, other viruses and even soem types of skin cancers, they are in form of creams

Imiquimod ( Aldara )
http://dreampharm.com/drugs-online/aldara/aldara.5.html

The genetic control of airway responsiveness and the effect of resiquimod treatment on allergic asthma
http://gradworks.umi.com/NR/68/NR68509.html

resiquimod
http://imgenex.com/get_details.php?catalog_no=IMG-2208

Imiquimod and resiquimod as novel immunomodulators
http://jac.oxfordjournals.org/content/48/6/751.full

[studyforhope]

The russian trial using myrcludex has started realistically on dec 12.2012.

The dosing was unfortunately chosen however in a range that cannot be expected to work effectively, if one takes into account the realistic analysis of human blood levels and dynamics curves from the phase I poster at the aasld 2012.  Thus even if the hepatera trial comes back with disappointing results, it does not mean that Myrcludex is not capable of working. It will have to be dosed higher to block with sufficient efficacy IMO..

It is also important to understand that in combo with Myrcludex the antivirals will have a clear direct synergistic effect on the efficacy of prevention of spreading of HBV into uninfected liver cells. This will become even more important when truly small levels of infected cells remain.

[stef2011]

thank you very much for your help, i ll give ezetimibe a try, i saw human studies with safety until a 50mg dose, i ll try 20mg

expetections from this are very very low but as you said it wont hurt or at beast help in the hcc/fatty liver prevention

do you know if any data is available about myrcludex human trials?any early hbsag drop in the combo arm?

[studyforhope]

I am sorry that the Imiqimod did not work.But this was foreseeable now for quite a while from the dynamics of your results.

Also the strophantin/ quauabin proposal from the hepatitis B foundation research group ..Timothy Block....to selectively kill infected cells has way to weak an effect to lend itself to in vivo human use.

[studyforhope]

I studied the ezetimibe paper from the Munich research group.
The pills for human use are 3mg. Considering the molecular weight of the compound, even the one micro molar concentration seems hardly achievable in vivo with this dose, unless it accumulates somehow in the liver after oral uptake. It is a fairly harmless compound, so testing it in the typical dosing does not seem to involve any major risk, but expectations that it will shift the total cccDNA content by influencing the speed of daily infection spread should be kept very low.
It's mode of action, according to the paper, is to block the processing of the incoming virions at a step later than the primary uptake.

[stef2011]

i just got hbsag result after another 3 months of suppository use of imiquimod and this lead to no results, hbsg remained stable at 4200iu/ml (previous result about 4400iu/ml, baseline about 7300iu/ml)

it is exactly like the alinia try, hbsag deosnt get to less than 4000iu/ml, at least for me

next try will be peg-intf alpha add on to my regimen of antivirals tenofovir plus entecavir and also started use of ezetimibe

[stef2011]

i just want to double check if 25mg suppository all at once have an effect on hbsag quant since from previous trial oral doses had no effect at all while the suppository ones who were very few like 25mg per month in april/may had a decrease of about 2000iu/ml in 3 weeks

since sides are none now and cost is extremely cheap i think it worths a try