肝胆相照论坛

标题: 对REP9AC、DV601等治愈乙肝科学研究的看法 [打印本页]

作者: kaorusai 时间: 2011-9-5 12:42 标题: 对REP9AC、DV601等治愈乙肝科学研究的看法

本帖最后由风雨不动于 2012-4-14 14:45 编辑

我关注论坛很久了，刚刚注册...
关注了这么久的乙肝新药的前瞻，今天谈谈我的看法

首先是大家期待的REP 9AC,这个药物可能是真的，我研究了一下网友贴的那8个人的实验结果，有5人表面抗原转阴，其中有一人DNA复制降不下来，8人中其中只有4个人治愈过，4个人中有1人复发且再用药物无效，也就是说8人之中只有3人有效治愈。试验中肝功能有爆发升高的迹象...所以说这药的疗效并没有文字报道的那么好，也许就是没有大肆报道的原因，临床1期治愈率就这么低，要是接下来的实验结果不好就没戏了，情况很不乐观....即使上市了有效率应该和长效干扰素差不多吧..、

h t t p://tr s.sc ivee.tv/n ode/1398 8人的实验数据（去掉空格）

然后是DV601，疗效无法跟REP9AC相比，“8名大三阳患者中有2人产生抗HBe抗体，有2人HBeag被清除，并且其中一人的表面抗原消失”，感觉效果不怎么样，和核苷类抗病毒药物差不多的。

最后就是入胞抑制剂myrcludex-B和SALP，这个遥遥无期了，等10年能出来就不错了，而且还不知道效果怎么样...

其实我是很期待REP 9AC的，虽然不乐观，但我希望这个药物能够改良取得更好的结果，这是目前最有希望的药物了....

请大家来拍砖讨论

我就知道这么多...现在我的情况不太好，拉米耐药了，肝功能处于边缘，我该怎么办...我很希望治愈乙肝的药物出现啊！

(6.合.彩).足球.篮球...各类投注开户下注

第一投注.现金网:招代理年薪10万以上:6668.cc

作者: jsmscym 时间: 2011-9-5 13:21

新药研发有50%的成功率，就算是成功了。不一定都要达到100%的。

作者: kaorusai 时间: 2011-9-5 13:25

jsmscym 发表于 2011-9-5 13:21
新药研发有50%的成功率，就算是成功了。不一定都要达到100%的。

是这样啊...我很希望REP 9AC能够成功，给我们带来希望，听说这药会在11月份的美国年会上公布新数据，让人期待

作者: StephenW 时间: 2011-9-5 13:45

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[attach]237088[/attach]

作者: kaorusai 时间: 2011-9-5 13:51

本帖最后由 kaorusai 于 2011-9-5 13:52 编辑

对，就是这个，第一、三、六个成功了。第二个好像复发了。第四个表面抗原好像转阴了，可是DNA还在复制，其他几个没什么效果

作者: StephenW 时间: 2011-9-5 14:02

kaorusai 发表于 2011-9-5 12:42
我关注论坛很久了，刚刚注册...
关注了这么久的乙肝新药的前瞻，今天谈谈我的看法

"有5人表面抗原转阴，" - 同意.
"其中有一人DNA复制降不下来" - (05B)不完全同意, 下降但不为0.
"8人中其中只有4个人治愈过" - 报告说3个人治愈.
"4个人中有1人复发且再用药物无效" - (02B) ?
"也就是说8人之中只有3人有效治愈。" - 同意.报告说相同:
three of these patients have achieved complete control of their infection after 20-27 weeks of treatment (HBV DNA -, HBsAg -, HBeAg -, anti-HBs +, anti-HBe +) and are being followed off treatment. These 3 patients are currently maintaining control over their infections 14, 27 and 52 weeks after stopping treatment.
这些患者中的三个都取得了完全控制其感染后20-27周的治疗（HBV - DNA - 乙肝表面抗原 - ，e抗原 - 抗- HBs，抗- HBe+），并正在遵循了治疗。这3例患者目前保持在控制他们的感染，14，27及52周停止治疗后，。

作者: StephenW 时间: 2011-9-5 14:07

本帖最后由 StephenW 于 2011-9-5 15:11 编辑

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"然后是DV601，疗效无法跟REP9AC相比，“8名大三阳患者中有2人产生抗HBe抗体，有2人HBeag被清除，并且其中一人的表面抗原消失”，感觉效果不怎么样，和核苷类抗病毒药物差不多的。" - 言之过早。不要忘了，结果从一个有限时间的治疗.

作者: StephenW 时间: 2011-9-5 14:10

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"最后就是入胞抑制剂myrcludex-B和SALP，这个遥遥无期了，等10年能出来就不错了，而且还不知道效果怎么样..."

Myrcludex - 已经
开始第1阶段的临床试验。

作者: kaorusai 时间: 2011-9-5 14:16

"其中有一人DNA复制降不下来" - (05B)不完全同意, 下降但不为0.-----指的是05B,没降到正常值，有待观察吧
"4个人中有1人复发且再用药物无效" - (02B) ?----对，是02B，
不知道为什么表面抗原降下来,DNA还在复制，我不是专家，真不清楚

作者: kaorusai 时间: 2011-9-5 14:21

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Myrcludex - 已经
开始第1阶段的临床试验？？

期待它的效果...

作者: StephenW 时间: 2011-9-5 14:32

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"请大家来拍砖讨论" -
http://www.hbvhbv.com/forum/thread-1067454-1-1.html
http://www.hbvhbv.com/forum/thread-1066205-1-1.html

这是从Replicor的CEO:
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...."

作者: 走遍四方 时间: 2011-9-5 14:44

Our current SVR rate is at 50 %.

作者: kaorusai 时间: 2011-9-5 14:49

本帖最后由 kaorusai 于 2011-9-5 15:02 编辑

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这些信息很有用！谢谢
治愈型疫苗的确很不靠谱.....
REP9AC 治愈率不到50%，太低了，这个专家说要开发什么联合治疗的提高SVR吧

CEO居然说估计3、4年能上市吧...以现在的治愈率恐怕很难..

难道我们只有寄希望于RNAI技术的成熟？

作者: StephenW 时间: 2011-9-5 15:07

kaorusai 发表于 2011-9-5 14:49
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这些信息很有用！谢谢

据studyforhope，未来最有可能
是组合治疗。最主要的是更多的临床试验。理论无法预测一切。

作者: StephenW 时间: 2011-9-5 15:20

本帖最后由 StephenW 于 2011-9-5 15:21 编辑

kaorusai 发表于 2011-9-5 14:16
"其中有一人DNA复制降不下来" - (05B)不完全同意, 下降但不为0.-----指的是05B,没降到正常值，有待观察吧
" ...

02B - ALT, HbsAg是相当不错的.

"不知道为什么表面抗原降下来,DNA还在复制，我不是专家，真不清楚 " -
据studyforhope，REP9AC停止乙肝表面抗原包覆颗粒（非感染）的形成和释放，而不停止新病毒颗粒的生产和释放. 要停止DNA复制, 可以用antivirals.

作者: kaorusai 时间: 2011-9-5 15:38

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02B - ALT, HbsAg是相当不错的.------------我也觉得相当不错了

治疗乙肝并不要求完全治愈，只要控制病情能够保证不复发目的就达到了

作者: StephenW 时间: 2011-9-5 17:38

本帖最后由 StephenW 于 2011-9-5 17:38 编辑

Dr. Mamun-Al-Mahtab医生是主管Rep9AC的临床试验.

"As the General Secretary of the Organizing Committee, I am pleased to inform you that Association for the Study of the Liver, Dhaka, Bangladesh (ASLDB) - the national Association of Hepatologists of the country, is going to organize the APASL 3rd STC on HBV Dhaka, Bangladesh from December 7 to, 2012. Your active participation is most vital in making this biggest even of Hepatology in Bangladesh a success and will surely go a long way in furthering Hepatology in this country.

On behalf of the Association members, I request your active participation in this meeting. Please mark the dates in your calender in advance, circulate this information among your friends and colleagues and encourage all to submit abstracts to the meeting.

We promise you some memorable times in Dhaka!

Thanking you.
Kind regards,

Dr. Mamun-Al-Mahtab (www.drmahtab.org)
Editor, LIVER: A Complete Book on Hepato-Pancreato-Biliary Diseases
Editor, Comprehensive Text Book of Hepatitis B
Secretary General, Association for the Study of the Liver, Dhaka, Bangladesh
Secretary General,Viral Hepatitis Foundation Bangladesh
Assistant Professor of Hepatology, Bangabandhu Sheikh Mujib Medical University
Deputy Editor-in-Chief, Euroasian Journal of Hepato-Gastroenterology
Deputy Editor-in-Chief, Clinical and Experimental Medical Journal
Editorial Board Member, Journal of Clinical and Experimental Hepatology
Journal of Global Infectious Diseases, Hepatitis Monthly, Microbiology Research
[attach]237190[/attach]

作者: hoimes 时间: 2011-9-5 19:41

关键是表面抗体的出现机率，有5个人出现了，但不幸的是有人（2人）表抗又阴转了，说明体内病毒复制数量很大未得到抑制。我想进入临床时，应结合核苷类药物，先把DNA转阴，病毒负荷降到最低，然后再使用REP9ac，一举完全消灭病毒，同时由于病毒载荷低，引起的免疫反应不致过于激烈。傻瓜才会使用单一药物吧。

作者: hoimes 时间: 2011-9-5 19:48

再补充一点，最后两个之治疗了13周，而前6个人有5人表面抗原阴转，现在所有药物治疗一年表面抗原转阴的概率不高于1%，楼主的分析太粗了。

作者: kaorusai 时间: 2011-9-5 20:08

StephenW 发表于 2011-9-5 17:38
Dr. Mamun-Al-Mahtab医生是主管Rep9AC的临床试验.

"As the General Secretary of the Organizing Committe ...

我的英语能力很糟糕....

作者: kaorusai 时间: 2011-9-5 20:09

hoimes 发表于 2011-9-5 19:41
关键是表面抗体的出现机率，有5个人出现了，但不幸的是有人（2人）表抗又阴转了，说明体内病毒复制数量很大 ...

你说得对，要是这药真能成功，将会给治疗带来新选择

作者: StephenW 时间: 2011-9-5 20:26

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“作为组委会的秘书长，我很高兴地通知你，为肝脏研究协会，孟加拉国达卡（ASLDB） - 国家协会全国肝病，是要组织APASL第三STCHBV达卡，孟加拉国从12月7日，2012年在孟加拉国取得成功，最大的甚至肝病您的积极参与是最重要的，必将在推动这个国家的肝病很长的路要走。

代表该协会的成员，我要求你在本次会议的积极参与。请注明在您的日历中的日期提前，您的朋友和同事之间的信息流通这个，并鼓励所有向会议提交论文摘要。

我们承诺在达卡的一些令人难忘的时代！

感谢你。
亲切的问候，

Dr 马蒙
- AL- Mahtab（www.drmahtab.org）
编辑，肝：肝胰胆系疾病的完整图书
编辑器，B型肝炎的综合教科书
肝脏研究协会秘书长，达卡，孟加拉国
秘书长，病毒性肝炎基金会孟加拉国
Bangabandhu谢赫穆吉布医科大学肝病，助理教授
副主编，行政，欧亚肝，胃肠病学杂志
副主编，行政，临床和实验医学杂志“
编委会成员，肝病临床和实验研究
全球传染病，肝炎月刊，微生物学研究

作者: kaorusai 时间: 2011-9-5 21:20

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StephenW你被邀请了吗？？而且还是在达卡........无论是APASL还是AASLD我们总是期待有些里突破性的东西能够出来。

作者: StephenW 时间: 2011-9-5 21:37

kaorusai 发表于 2011-9-5 21:20
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StephenW你被邀请了吗？？而且还是在达卡........无论是APASL还是AASLD我们总是期待 ...

不，我不是一个研究者。无需参加，我们可以读发表的论文.

作者: hoimes 时间: 2011-9-6 01:12

DV601的效果实际上也不错，公告里好像说8个小三阳4个表面抗原阴转。感觉dv601或rep9ac只要有一个能成功上市，都比现在的药物最终治疗效果要好许多，还是很有希望的。

作者: V友 时间: 2011-9-6 09:40

本帖最后由 V友于 2011-9-6 15:35 编辑

我想这是新药研究理念的一个新的突破，对乙肝来说不久的将来是很有希望的，但远期疗效及安全性如何有待观察。如果成功了，临床还可能联合用药，抗病毒药就象抗菌素一样

作者: kaorusai 时间: 2011-9-6 17:32

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“ REP9AC'会更好的耐受性(tolerated)比REP9AC，它将更快地消除了乙肝表面抗原和将更容易管理(administered)”

不知道 REP9AC'是个什么东西，会比REP9AC好多少 ......

作者: 苹苹苹 时间: 2011-9-6 17:48

期待早点出来

作者: 虎哥很迷茫 时间: 2011-9-6 18:34

黎明的曙光

作者: kaorusai 时间: 2011-9-6 19:06

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广大的战友都希望在自己的肝硬之前能够有特效药出来

作者: StephenW 时间: 2011-9-6 19:51

本帖最后由 StephenW 于 2011-9-6 19:51 编辑

kaorusai 发表于 2011-9-6 19:06
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广大的战友都希望在自己的肝硬之前能够有特效药出来

"自己的肝硬" - 没有必要会成为肝硬化，如果你可以保持你的ALT<30（男），19（妇女）.

作者: kaorusai 时间: 2011-9-6 19:57

StephenW 发表于 2011-9-6 19:51
"自己的肝硬" - 没有必要会成为肝硬化，如果你可以保持你的ALT

我有耐药的现象，我也希望我的ALT能保持正常，但谁能保证一直正常呢？哎.....

作者: StephenW 时间: 2011-9-6 20:07

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"但谁能保证一直正常呢？" - 因此，不要过于担心，定期在阳光下运动, 不吸烟，不喝酒，你会活到100

作者: 把握当下 时间: 2011-9-6 20:09

hoimes 发表于 2011-9-5 19:41
关键是表面抗体的出现机率，有5个人出现了，但不幸的是有人（2人）表抗又阴转了，说明体内病毒复制数量很大 ...

严重赞同联合核苷，一个干掉dna，一个干掉表面抗原，这样金牌就不是梦啦~~

作者: 大哥是陆军 时间: 2011-9-6 20:12

硬之前一定要上市啊

作者: kaorusai 时间: 2011-9-6 21:10

StephenW 发表于 2011-9-6 20:07
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"但谁能保证一直正常呢？" - 因此，不要过于担心，定期在阳光下运动, 不吸烟，不喝 ...

谢谢你的鼓励

作者: 南来飞鸿 时间: 2011-9-7 01:32

乙肝终结者：REP9AC+替诺

作者: 蔡小楠 时间: 2011-9-13 10:43

很不错啦！

作者: mingbai 时间: 2011-9-18 12:58

每次上论坛，都直奔这里，看看有没有新希望。感谢汇报消息的战友们，有个希望，哪怕是渺茫的也让我有了生活的勇气

作者: supersonicbear 时间: 2011-9-20 20:07

潜水好久，这次决定顶贴
希望早日上市啊

作者: 石榴主人 时间: 2011-9-24 12:37

关注中

作者: 三国杀 时间: 2011-9-27 10:37

没看懂呀，这是阻断乙肝哪个方面，原文出处在哪里？

作者: 三国杀 时间: 2011-9-27 10:38

而且8个人，例数太少了吧

作者: StephenW 时间: 2011-9-27 13:57

本帖最后由 StephenW 于 2011-9-27 13:58 编辑

studyforhope 在Medhelp上回答 Rep 9AC问题:

[4est]:
Let assume that we have HbeAg negative, HbsAg suppress by Rep9Ac and DNA supress by antivirals. so, this is the best case for a chronic carrier (no e or s antigen for divert immune answer, no DNA means no new viruses), but also in this situation the cccDNA will remain in the liver cells. how this will be manage?
Can we assume that because we don't have s and e antigens the immune system will target the infected liver cells and destroy them ?

[studyforhope]:
That is the basic concept. In addition to the direct targeting by cd8 cytotoxic Tcells, the local phagocytosis of virions and debris from necrotic liver cells containing HBV proteins will allow presentation of the classII  peptide epitopes on the surface of Macrophages and Kupffer cells  to cd4 helperTcells in the liver, with a strong local cytokine response that will help in the noncytolytic clearance  of hepatocytes fromm HBVcccDNA.

One problem is likely that the longstanding exhaustion of the  s antigen specific T-cell clone repertoire (many many years of periphery flooding with e and s antigens) will require a substantial time frame of regeneration of this immune response, particularly in older patients and those with a longer chronic infection. Thus a longer supression of s-antigen release by REp 9AC might be necessary  to allow targeted immune recovery in these patients.
Aside from protection against adaptive immune evasive epitope mutations by antivirals, it might also be advisable to accelerate the regeneration of the blunted adaptive immune response - TandB cells-  by therapeutic vaccinations once the s-antigen is negative.

Regarding new developments on the horizon, there is a therapeutic HBV vaccine by Dynavax, that could be used eg in the context above. Replicor and Myrcludex remain the most promising partial attack modes against HBV at this moment.
The liver concentrating tenofovir would be a great element of progress, since reduction in antiviral toxicity is a major concern, consdering the need for long term use.
Nitazoxanide thus far - see Stefs progress reports- seems to be of weak effectiveness, at least at the dosing that is low enough for comfort.

Substances like squalamine might be virus propagation blocking to a certain degree, but the effect on the reduction of the cccDNA hepatocyte population is unlikely to be better than the one with antivirals. It is too early to make any specific predictions.

作者: StephenW 时间: 2011-9-27 14:02

[4est]:
Rep9AC will suppress HBsAg and in this case we can produce HBsAb ? and what happen if ccDNA will remain in some liver cells ? will be enough HBsAb to suppress HBsAg after the Rep9Ac treatment is stooped ? .

[studyforhope]
Providing that enough s antigen specific B cells are left or have recovered, there will be an antiHbs antibody titer.
If, after REP9AC is stopped only a tiny amount of infected cccDNA containing cells are left after immune clearance, then the antibody will be sufficient to neutralize this very very small amount of surface antigen.
The key is the suffcient reduction of the cccDNA containing hepatocye pool PLUS a remaining population of HBV antigen specific Tcells in the liver to help supress the synthetic and replicative activity of this small cell pool by a local permanent cytokine milieu, that will inhibit transcription , replication and possibly translation of the HBVgenomes that will still reside in the liver, just as is the case with persons with acute recovered Hepatitis B - for a lifetime, without outside intervention.

It needs to be understood, that the antiHbS antibody is only protecting against reinfection. The key long term controlling factor is a long lasting antigen specific Tcell response residing in the liver.

Only in case of a cancer chemotherapy or intense antinflammatory therapy with TNFalpha inhibitors such remnant HBV clusters tend to regrow and reactivate, since the permanent watchdog forces are now of diminshed activty - a process called REACTIVATION. It is now becoming routine to protect against such reactivations in prior acute recovered HBV cases or chronic cleared HBSseroconverters with temporary antivirals during such treatments.

作者: cwy121 时间: 2011-9-27 14:10

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我靠，你是中国人还是外国人啊？不要老整英文嘛，看不懂啊！

作者: 走遍四方 时间: 2011-9-27 14:13

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朋友别怪他，没办法，最先进的都是英文的。。。木有法子。。

作者: alex1234 时间: 2011-9-29 19:49

变异率太高了。。。。

作者: kaorusai 时间: 2011-10-3 13:17

刚在网上看到了关于Myrcludex的这样一个信息
The completion of Phase 1 and the start of the „proof-of-concept“ Phase 2 study are planned for 2012.

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

这样下去Myrcludex要是能成功的话应该比REP9AC要快！

作者: StephenW 时间: 2011-10-3 15:30

本帖最后由 StephenW 于 2011-10-3 15:31 编辑

kaorusai 发表于 2011-10-3 13:17
刚在网上看到了关于Myrcludex的这样一个信息
The completion of Phase 1 and the start of the „proof-of- ...

"这样下去Myrcludex要是能成功的话应该比REP9AC要快！" - 这是可能。但我们应该记住，Mycrludex本身是不够治愈.

Myrcludex presentation at the San Francisco liver conference.
Conclusions: Myrcludex-B showed strong capacities to prevent HBV spreading in vivo. Since maintenance of chronic HBV infection involves a dynamic turnover between cells that are cleared by the immune system and cells that become newly infected, the use of drugs preventing hepatocyte re-infection, possibly in combination with other HBV-drugs, may represent a new effective antiviral concept also in the setting of chronic infection.

Myrcludex旧金山肝会议的演示。
结论：Myrcludex- B的表现出较强的防止乙肝病毒在体内扩散的能力。
由于慢性乙肝病毒感染的维护包括一个动态的营业额是由免疫系统，并成为新感染的细胞，防止肝细胞再感染的药物的使用可能在与其他乙肝病毒药物的组合，清除细胞之间，可能代表了一种新的有效抗病毒药物的概念在慢性感染的设置。

作者: StephenW 时间: 2011-10-3 15:38

[studyforhope]
Myrcludex blocks the entry of HBv into hepatocytes. That is all it does. Over time, that should indirectly reduce the pool of infected cells, by whatever means this reduction is operative, mainly the ongoing erosive immune attack, that causes the ALTs to be elevated. The question is really right now, how effective will the planned dose of Myrcludex of 1mg/day be in achieving this effect.

If the reduction of infected cells and therefore the cccDNA has come down to a level, where the surface antigen disappears from the circulation, then permanent immune control of the infection is likely, even after stopping myrcludex.

Myrcludex and Replicor would beautifully complement each other, since the effects are on entirely different aspects of the viral mechanisms.

Replicor blocks the release of the surface antigen particle from infected hepatocytes, not of any virions. It does that with great reliability and apparently very little side effects.
That effect per se however is not blocking the virus from replicating or directly reduces the cccDNA. What happens now is that the removal of the surface antigen allows the immune system to focus its anti surface effector cells on the liver and that will lead to an increased removal of infected cells, plus reduction in viral replication and transcription by noncytolytic mechanisms and ,unless the virus is able to respond evasivly, to a reduction of the infected cell number and the cccDNA to a level where permanent immune control of the remnant amounts will be possible, without outside medications.
Myrcludex would help in the speed of this process by preventing reinfection, speeding up clearance and, quite importantly, prevent any immunologically resistant subpopulation from spreading, thus ensuring the success of the REP9A treatment.

Myrcludex阻止乙肝病毒进入肝细胞的条目。这是它所做的一切。随着时间的推移，这应该间接地减少感染的细胞池，通过任何手段减少操作，主要是持续的糜烂性免疫攻击，导致升高的异常低价竞标。问题是真的，现在，如何有效地将1mg/day Myrcludex计划剂量达到这种效果。

如果减少感染的细胞，因此cccDNA的已回落到一定程度，表面抗原从流通中消失，然后永久感染的免疫控制是可能的，即使停药后myrcludex。

Myrcludex和Replicor精美相得益彰，因为病毒的机制是完全不同的方面的影响。

Replicor块释放从被感染的肝细胞的表面抗原颗粒，而不是任何病毒粒子。它具有高可靠性，显然是很少的副作用。
然而，这本身的影响是不阻止病毒复制，或直接降低了cccDNA的。现在会发生什么是表面抗原的清除，允许免疫系统，以集中其抗表面效应细胞对肝脏和，这将导致增加感染细胞的清除，再加上在减少病毒复制，并通过非溶细胞机制转录和，除非病毒是能够回应闪烁其词，没有一个被感染的细胞数量的减少和cccDNA的水平将有可能永久的残余量的免疫控制外药物。
Myrcludex将有助于这一进程的速度，防止再感染，加快通关，很重要的是，防止火势蔓延任何免疫抗亚群，从而保证了成功的REP9A治疗。

作者: kaorusai 时间: 2011-10-3 16:07

StephenW 发表于 2011-10-3 15:38
[studyforhope]
Myrcludex blocks the entry of HBv into hepatocytes. That is all it does. Over time, t ...

Myrcludex和REP9A联合用药？？？

作者: kaorusai 时间: 2011-10-3 16:10

Mycrludex本身是不够治愈？？
这真是个不幸的消息啊

作者: StephenW 时间: 2011-10-3 16:57

本帖最后由 StephenW 于 2011-10-3 16:58 编辑

kaorusai 发表于 2011-10-3 16:10
Mycrludex本身是不够治愈？？
这真是个不幸的消息啊

很难说, Mycrludex，防止感染和再感染, 会帮助我们的免疫系统来清除所有的感染的肝细胞（与其cccDNA）。加上REP9AC，HBsAg水平下降，免疫系统可以集中精力清除感染的肝细胞（与其cccDNA），因此会很快治愈。这是理论，我们必须等待，看看它是否是真正的,临床试验后。

作者: kaorusai 时间: 2011-10-3 17:16

但愿这个理论能变为现实
Mycrludex到底是德国那个公司的？临床1期需要一年，临床2期需要2年，三期好像需要三年，通过FDA还要两年。那么就要等到2020年了.....太漫长了！

作者: StephenW 时间: 2011-10-3 17:37

kaorusai 发表于 2011-10-3 17:16
但愿这个理论能变为现实
Mycrludex到底是德国那个公司的？临床1期需要一年，临床2期需要2年，三期好像需要 ...

如果一种药物是好的，SDF可以快车道(fast track).
德国MYR GmbH, 非常小的公司

About the MYR GmbH
The company located in Burgwedel near Hannover was founded in 2010 and holds the world-wide exclusive product rights for Myrcludex. Currently, the company has 2 employees who are focused on the coordination of the network of academic partners and vendors involved in the Myrcludex development. Dr. Alexander Alexandrov, MYR CSO: „We have established a very successful public-private partnership giving birth to a promising and efficient Biotech-company“.
投资公司Gründerfonds
About High-Tech Gründerfonds
High-Tech Gründerfonds invests venture capital in promising technology companies that turn innovative concepts into viable businesses. Seed financing aims to help start-ups guide their innovation to the prototype or proof-of-concept stage or to market launch. High-Tech Gründerfonds provides seed financing of approximately €500,000. It supports high-tech companies by way of its investment managers and its highly-qualified network of coaches, investors and specialists. In individual cases it can invest up to a total of €2 m per company. The investors in this public private partnership are the German Federal Ministry for Business and Technology, the KfW Banking Group as well as the six industrial groups of BASF, Deutsche Telekom, Siemens, Robert Bosch, Daimler and Carl Zeiss. High-Tech Gründerfonds has an investment volume totalling approx. €272 m.

作者: kaorusai 时间: 2011-10-3 18:14

StephenW 发表于 2011-10-3 17:37
如果一种药物是好的，SDF可以快车道(fast track).
德国MYR GmbH, 非常小的公司

也是小公司啊......看来小公司能出好产品

作者: 2012痊愈 时间: 2011-10-6 17:22

赶紧上市，造福人类

作者: StephenW 时间: 2011-10-8 03:20

本帖最后由 StephenW 于 2011-10-8 03:20 编辑

Myrcludex演示文稿 - 旧金山, 肝病学会2011
[posted by studyforhope]

Myrcludex presentation at the San Francisco liver conference.

The entry inhibitor Myrcludex-B efficiently blocks viral spreading in vivo in human liver chimeric uPA/SCID mice previously infected with Hepatitis B Virus
M. Lutgehetmann1, 2; J. Petersen3; T. Volz1; L. Allweiss1; A. W. Lohse1; S. Urban4; M. Dandri1
1. Internal Medicine, University Hospital Hamburg Eppendorf, Hamburg, Germany.
2. Medical Microbiology, University Hospital Hamburg Eppendorf, Hamburg, Germany.
3. Asklepiosklinik St. Georg, Liver Center Hamburg IFI Institute, Hamburg, Germany.
4. Infectious Diseases, University Hospital Heidelberg, Heidelberg, Germany.

Currently approved antiviral treatments based on interferon alpha or inhibitors of the hepatitis B virus (HBV) polymerase are generally not curative and additional therapeutic strategies interfering with other HBV replication steps are needed. We previously demonstrated prevention of de novo HBV infection by pre-treating uPA mice with Myrcludex-B, a lipopeptide derived from the preS1 domain of the HBV envelope (Nat. Biotech.2008). Aim of this study was to investigate the ability of this HBV entry inhibitor to block viral spreading post-infection, at a time when viremia is already detectable but only few human hepatocytes are infected. Experimental design: human liver chimeric uPA/SCID mice were injected with HBV-infectious serum (5x10E7 HBV DNA copies/mouse) and treatment with Myrcludex-B (2 mg/Kg/day; s.c. injection) was initiated either 3 days (group A, n=8) or 3 weeks (group B, n=7) post HBV-inoculation, while 8 sham-treated mice were used as control. Mice were analyzed serologically (HBV-DNA, HBsAg) and intrahepatically by quantitative RT-PCR measurements (cccDNA) and immunohistochemistry (human CK-18, HBcAg) at baseline, after 3 and 6 weeks of treatment. Results: In the first experimental setting, Myrcludex-B administration initiated 3-days after HBV-inoculation efficiently prevented viral spreading from the few initially infected human hepatocytes, as demonstrated by immunohistochemistry. Viremia and HBsAg levels remained below 10E5 HBV-DNA/ml and <10 IU/ml, respectively, while in untreated control mice median viremia increased to 3x10E7 and the majority of human hepatocytes stained HBcAg-positive within six weeks post-infection. Occurrence of viral spreading was also demonstrated in 2 mice after therapy discontinuation. Furthermore, Myrcludex-B blocked viral spreading even when treatment was first initiated at 3-weeks post-infection, at a time when median viremia was 2x10E6 HBV-DNA/ml. Notably, levels of viremia, HBsAg and intrahepatic cccDNA loads did not increase significantly after 6 weeks of treatment. Conclusions: Myrcludex-B showed strong capacities to prevent HBV spreading in vivo. Since maintenance of chronic HBV infection involves a dynamic turnover between cells that are cleared by the immune system and cells that become newly infected, the use of drugs preventing hepatocyte re-infection, possibly in combination with other HBV-drugs, may represent a new effective antiviral concept also in the setting of chronic infection.

作者: StephenW 时间: 2011-10-8 03:24

REP 9AC论文摘要 - 旧金山, 肝病学会2011
[posted by studyforhope]

Here is the current abstract for REP9AC at the upcoming San Francisco AASLD liver conference 2011:
REP 9AC: A potent HBsAg release inhibitor that elicits durable immunological control of chronic HBV infection.
M. A. Mahtab2; M. Bazinet1; A. Vaillant1
1. REPLICor Inc., Montreal, QC, Canada.
2. Bangabandhu Sheikh Mujib University, Dhaka, Bangladesh.

BACKGROUND: HBsAg plays a critical role in suppressing the immune system and is the likely mechanism for the chronicity of HBV infection. REP 9AC is a nucleic acid-based amphipathic polymer (NAP) which inhibits the release of HBsAg from infected hepatocytes. Previous interim clinical data has shown that REP 9AC rapidly clears serum HBsAg in infected patients and allows patients to regain durable immunological control over their HBV infection. An updated progress report of the ongoing phase I/II study on the safety and efficacy of REP 9AC in patients with chronic HBV (CHB) infection is presented.
METHODS: All patients were HBsAg+ with pre-treatment HBV DNA titers between 106 and 1012 copies/ml. Additionally, all patients were shown to have significant liver fibrosis as assessed by pre-treatment liver biopsy. Patients with CHB were subjected to parenteral REP 9AC therapy. Safety and virologic response (HBV DNA [Roche Cobas ™], HBsAg, anti-HBs [Immunilite]) were assessed weekly at the trial site/. Off site confirmatory testing of HBsAg, HBeAg, anti-HBs, anti-HBe was conducted using the using the Architect ™ platform.
RESULTS: Interim data shows that 7 out of 8 patients treated to date have either cleared or have only residual levels of serum HBsAg and anti-HBsAg antibodies have been observed in all patients. Clearance of HBsAg and development of anti-HBs have been observed as early as 7 days and no later than 32 weeks. At the time of abstract submission, 6 out of 7 patients with serum HBsAg reductions had achieved a 3 to 7 log reduction in their HBV DNA titers from pre-treatment levels after 7-13 weeks of treatment. Additionally, three of these seven patients have achieved a complete control of their infection with 20-27 weeks of treatment (HBV DNA < 400cpm-, HBsAg -, HBeAg -, anti-HBs +, anti-HBe +) and are being followed off treatment. These three patients have demonstrated durable immunological control over their infections, having SVRs of 18 months, 12 months and 10.5 months after cessation of treatment.
CONCLUSIONS: These results demonstrate that REP 9AC can rapidly and effectively clear HBsAg from the serum of infected patients. This rapid HBsAg seroclearance appears to allow the restoration of an effective immune response, as evidenced by substantial reductions in serum HBV DNA, seroconversion for HBsAg and HBeAg, and the achievement of SVRs in three patients to date. These results suggest that REP 9AC may become an important new tool in the treatment of chronic hepatitis B.

作者: 潇洒书生 时间: 2011-10-8 13:10

除了期待还是期待. . . . .

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