Talk:Rintatolimod

message: I feel that the entire 'Mechanism of Action' section is a bit confusing/weak and probably misleading/wrong. Perhaps you could help out? Thedreamdied 22:09, 29 January 2007 (UTC)
replies: text: OK i put in some mechanism stuff. I can put in the references, reviews i guess i will have to pick some. I am thinking some one can tell me more, how does this work, BC it says RNase L is elevated in CFS, that is causing the problems. Ampligen stimulates RNase L production, how does that help is it desensoritization or does any one know? I am curious now thx RetroS1mone talk 05:29, 9 January 2009 (UTC)
replies: text: If you have access to full text try this review . These are researchers that have published most on the subject in CFS. The problem as I know it is that excess low molecular weight 37 Kd RNase L (higher 37-Kilodalton/83-Kilodalton RNase L Isoform Ratio) found in CFS patients up-regulates the pathway. After Ampligen treatment the 37 Kd RNase L levels have been reported to be reduced. From there my knowledge is fragmentary. Ward20 (talk) 20:04, 9 January 2009 (UTC)
replies: text:  With the assistance of experts on Ampligen, I am attempting to provide helpful edits to this page in the section below called proposed changes. I will propose sections at a time until the page is updated in its entirety. BluebirdHill5 (talk) 14:48, 5 April 2017 (UTC)
thread_title:  Expert Help 

message: Blanking the article is unhelpful: and suggesting that "The entire Ampligen entry is incorrect and needs to be rewritten by a specialist" with the explanation "It was for the greater part incorrect, misleading and biased" is unhelpful - where is it incorrect, where is it misleading, and why is it biased? Feel free to correct any errors you see, with valid sources. Thedreamdied 23:12, 9 February 2007 (UTC)
thread_title:  With regard to [[User:Zanzibarlo]] and [[User:Zarzine]] 

message: For all citations, a separate entry in the References section is required. I added one citation with a template as footnote, but maybe you prefer to stick with embedded citations, in which case the references need to be added separately another time. Tikiwont 10:32, 14 February 2007 (UTC)
replies: text: Please review WP:CITE for information on how to include inline citations in articles. The 'references' section is for inline citations. If you want to add extra titles that are not cited by the article text, they would go in a 'further reading' section. Dr. Cash 00:41, 27 February 2007 (UTC)
thread_title:  Citations 

message: I'm not sure its really that relevant to the article to have so much about it. Perhaps a 'Hemispherx Biopharma' article could be created, with an explanation of their controversial history? Thedreamdied 14:46, 14 February 2007 (UTC)
replies: text: I think the fortunes of Ampligen are likely to be closely tied up with ALL the obstacles it has met on its way. So we should not forget one. But feel free to cut down the Asensio story if you think it is too wordy.Wamper 10:44, 15 February 2007 (UTC)
replies: text: Likewise, the fortunes of Hemispherx are likely to be closely tied up with the fortunes of Ampligen. Normally I would say that a separate company article is a good idea, but I'm not so sure in this case. The story of Ampligen is the story of Hemispherx. For now I've created two Hemispherx redirect pages. AvB ÷ talk 11:31, 15 February 2007 (UTC)
replies: text: Perhaps, but Hemispherx have other drugs, some of which i put on wikipedia, such as Alferon LDO, which are now ignored by the redirect to this article. Thedreamdied 14:24, 15 February 2007 (UTC)
replies: text: Generally, if the articles on the separate products would be small, we tend to write a single article on both the company and its products, redirecting the drug names to the main article. But you're right, I thought they only had Ampligen and Ampligen-derived Oragen. Since Alferon is clearly unrelated to Ampligen, it may indeed be useful to start a separate HEB article. I think we have sufficient content regarding the drugs themselves to warrant separate articles. AvB ÷ talk 14:50, 15 February 2007 (UTC)
thread_title:  Asensio etc 

message: According to here, Ampligen is mainly for CFS as well as HIV, which is barely mentioned in the article. AMP 720 is listed here, and there seems to be quite a lot of info available generally. Thedreamdied 15:39, 14 February 2007 (UTC)
thread_title:  Ampligen and HIV 

message: This article seems to be the subject of competing points of view, particularly in the "Controversy" section.  If there are any knowledgeable, yet uninvolved, editors that could help check this article for adherence to Wikipedia's neutral point of view policy, that would be helpful.  -- Ed (Edgar181) 16:56, 29 June 2009 (UTC)
replies: text: It seems ok to me. I did right it, of course, but it seems to present information reasonably fairly. Thedreamdied (talk) 11:39, 2 July 2009 (UTC)

text: It is hijacked?? Anon hijacks and does BLP and accuses someone they are not reputable. That is personal attack, BLP problem. Do you want, the article should say "The Street proved" or what is it?? I do not understand, i do not like BLP problem and I agree on Thedreamdied, it is neutral. I remove the tag. RetroS1mone talk 03:48, 14 August 2009 (UTC)
thread_title:  Neutral point of view 

message: Ward20 changed the lead from 'refused to approve' to 'refused marketing approval', but that doesn't seem to be what the source says. It just says they refused to approve it for treatment of CFS. --sciencewatcher (talk) 22:55, 12 February 2010 (UTC)
replies: text: Sorry, evidently my edit summary was poor, I should probably have explained it better on the talk page. Adam Feuerstein's article was a little sloppy in his first sentence in that he didn't mention specifically that the FDA's refusal was for Ampligen's New Drug Application (NDA). The philadelphia bizjournals source I added clarifies the refusal was for the NDA. The NDA is concerned with marketing approval of the drug, not experimental usage. The Ampligen NDA was filed in 2007. (See page three, last paragraph of Feuerstein's article and the Press Release - NDA filing of Ampligen for CFS for verification. A different FDA approval process called  Investigational New Drug (IND) (the step before NDA marketing approval) is concerned with experimental usage of Ampligen. There are no statements the IND usage for Ampligen is affected, and the sources state that the FDA wants Hemispherx to do more clinical studies, which would be regulated under IND approval. Ampligen never had retail marketing approval, only experimental studies approval (including open label), and the FDA decision doesn't change the status quo. Ward20 (talk) 00:16, 13 February 2010 (UTC)
replies: text: I've tweaked it a bit. I removed the marketing bit because it's more than just marketing - it is for sale to the public. Saying they were refused marketing implies incorrectly that they just aren't allowed to advertise it. And because we already mention the NDA application in the previous sentence, I just added the rejection to the same sentence. I also added the reason (lack of proven efficacy), as that is important. --sciencewatcher (talk) 16:15, 13 February 2010 (UTC)
replies: text: Changes look good. I added "to market and sell Ampligen" to further address your concerns. Ward20 (talk) 19:11, 13 February 2010 (UTC)

text: LOL. I just noticed you already made the same changes to the Chronic fatigue syndrome treatment article so I guess we are on the same page. Ward20 (talk) 19:18, 13 February 2010 (UTC)
thread_title:  Marketing? 

message: Google scholar gives 1350 hits for Ampligen in (and 80 for Rintatolimod) excluding patents and refs. This seems plenty to establish that this is actually a notable substance, whether or not the current refs are any good. JMiall₰ 16:27, 15 April 2015 (UTC)
thread_title:  Proposed deletion 

message: Hello fellow Wikipedians,
I have just added archive links to  on Rintatolimod. Please take a moment to review my edit. If necessary, add  after the link to keep me from modifying it. Alternatively, you can add  to keep me off the page altogether. I made the following changes:
*Added archive https://web.archive.org/20060828141002/http://www.aegis.com:80/news/pr/1999/PR990509.html to http://www.aegis.com/NEWS/PR/1999/PR990509.html
*Added archive https://web.archive.org/20070204071235/http://www.cfs-news.org:80/amposler.htm to http://www.cfs-news.org/amposler.htm
When you have finished reviewing my changes, please set the checked parameter below to true to let others know.
Cheers.—cyberbot IITalk to my owner:Online 07:55, 18 January 2016 (UTC)
thread_title:  External links modified 

message: Intro: These proposed changes has been rewritten/reworked and the content reviewed and vetted by scientific experts in an attempt to improve the accuracy and quality of the information, including correcting broken and obsolete references. As noted in various sections of this talk page, this page is in need of expert help, the page contains statements that are not really useful about rintatolimod, and some information that is incorrect and/or biased.  
I propose the following changes. The current text proposed for deletion has been italicized. My comments are in CAPS. The new text is in regular font. If the proposed edits are approved, I will/can re-post the approved information in the wiki page and cite the references. Once this first section is reviewed, I have additional content to add I believe will be equally beneficial to this wiki page. I believe this new language is informative and provides useful information where the current page is a bit of a mess.  
Introduction:
 
1ST AND 2ND PARAGRAPHS OF CURRENT TEXT TO BE DELETED:
Rintatolimod, sold under the tradename Ampligen, is a medication intended for treatment of chronic fatigue syndrome.[1] However, there is only low-quality evidence that it can improve the ability to exercise.[1]- Reason for deletion: the second sentence if factually incorrect. If you read the article referenced, it clearly does not come to this conclusion and does not state this.
It is an immunomodulatory double stranded RNA drug synthesized in the 1970s and manufactured by Hemispherx Biopharma.[2]
Although Ampligen was cleared for use in Canada in 1997,[3] and obtained orphan drug status for treatment of CFS in the European Union in 2000,[4] it is so far without FDA approval, and therefore classed as experimental in the United States. In 2007, Hemispherx filed a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) to market and sell rintatolimod for the treatment of CFS,[5] but this was rejected in December 2009, because the FDA concluded that the two RCTs "did not provide credible evidence of efficacy"[6][7] and "because of clinical, statistical, clinical pharmacology, nonclinical, product quality, and facilities inspection deficiencies."[8] The FDA requested Hemispherx conduct at least one additional controlled trial to demonstrate efficacy in treating CFS. In August 2012, Hemispherx submitted further analyses of the original clinical trial data, but did not submit additional trials for review. Four months later, a committee of the FDA voted 8-5 against approval for rintatolimod, again citing insufficient data.[8] 
THE CURRENT TEXT ABOVE IS TO BE REPLACED WITH THE FOLLOWING:
Rintatolimod (brand name Ampligen®)   is a mismatched double stranded RNA (dsRNA). Rintatolimod activates Toll-Like Receptor 3 (TLR3), which results in transitory modulation of the cellular expression of hundreds of genes providing initial innate immune responses. Innate immunity provides initial resistance against invading viral pathogens and the later adaptive immune responses responsible for long term immunity. Among the genes responding to rintatolimod are the interferons (IFN) known to provide broad antiviral and growth inhibitory properties (Ref).  Rintatolimod activates IFN induced proteins that require dsRNA for activity (e.g.- 2ʹ-5ʹ adenylate synthetase, protein kinase R). Rintatolimod’s gene inducing activity is limited to activation of TLR3 (restricted TLR3 agonist), which minimizes systemic inflammatory cytokine responses (see mechanism of action below).Mitchell, William M.(2 June 2016). "Efficacy of rintatolimod in the treatment of chronic fatigue syndrome/Myalgic encephalomyelitis (CFS)".  Expert Review of Clinical Pharmacology. Volume 9, 2016 – Issue 6. doi http://dx.doi.org/10.1586/17512433.2016.1172960:. Retrieved 2017-4-4.
The branded product, Ampligen®, is owned and manufactured by Hemispherx Biopharma, Inc.[2](Ref)The properties of clinical grade rintatolimod and a molecular model of the activated rintatolimod:TLR3 dimer complex are summarized in Table 4.[1] Intellectual property for rintatolimod includes new form and substance patents in the US and Europe.[2]CURRENT CITATION CORRECTED: Gowen BB, Wong MH, Jung KH, Sanders AB, Mitchell WM, Alexopoulou L, Flavell RA, Sidwell RW (April 2007). "TLR3 is essential for the induction of protective immunity against Punta Toro Virus infection by the double-stranded RNA (dsRNA), poly(I:C12U), but not Poly(I:C): differential recognition of synthetic dsRNA molecules". J. Immunol. 178 (8): 5200–8. https://www.ncbi.nlm.nih.gov/pubmed/17404303:. Retrieved 2017-4-4.
BluebirdHill5 (talk) 20:57, 4 April 2017 (UTC)
replies: text: Hi BluebirdHill5, and thank you for your suggestions. I am not convinced that the information about lack of FDA approval should be removed from the lead. Therefore, I am declining this edit request. Nor do I agree that the second sentence in the existing paragraph should be removed: perhaps "low quality" is an imprecise term, so I replaced it with "low strength", which is exactly the term the article cited uses to describe the evidence on Rintatolimod's effectiveness. Altamel (talk) 03:03, 26 June 2017 (UTC)
replies: text: User:BluebirdHill5 thanks for bringing this to talk. I agree this does not appear to be an improvement thus support it not being implemented. Doc James (talk · contribs · email) 17:43, 26 June 2017 (UTC)
thread_title:  Proposed Article Changes 

message: I just updated url and formatted sources in the lead section, and marked a few dead links. I added copy re Canada and Argentina. I updated the official web site for Hemispherx in the lead as well. Lots of the refs are used only in the lead, which is not best form for Wikipedia. The lead is meant to highlight the article’s contents, so the refs ought to be somewhere in the article as well. I might copy a section of the lead into a new section on Status across the world. I am not usually editing articles on drugs, and do not know if there are special rules, like for the articles on diseases. 
:Lots of references in the main body of the article are dead links today, but I have no more time just now to hunt for updated links. I can share that FDA has its own search page for archived links. Follow the link in the article, get the FDA page saying “we cannot find this”, go their archive page and insert the old url in search bar, click to search archive and see what you get. If you get a usable url, then keep the old url in the ref and add the new one as archive-url and add the archive-date, provided on the FDA page. 
:Sources provided on this page here might improve this article. I had no idea that Ampligen was still in use, and was quite pleased to find this article. I hope it can get updated further and cleaned up a bit. - - Prairieplant (talk) 23:10, 17 May 2021 (UTC)
replies: text: The ref name fda1 was apparently used more than once in the article and needs clearing up. It generates an error message. - - Prairieplant (talk) 00:07, 18 May 2021 (UTC)
thread_title:  Needs updating