Talk:TGN1412

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Date of review: 2007-01-02

Contents

[edit] Introduction

Shouldn't there be a brief mention of the drug trial incident in the opener, seeing as that's why the drug is particularly notable? Amo 18:04, 17 May 2006 (UTC)

I agree. Added. Carcharoth 11:12, 23 May 2006 (UTC)

[edit] New development, needing proper source

Translated from a Danish web news page, [1]:

Swollen men victims of "fusk" (fraud?).
20-05-06: 11:02
When six Brittish men suffered from a medical test going wrong in England, they were victims of serious errors from the medical company, writes Politiken [2].
...
A standard analysis in a computer model shows that the medical experiment never should have been approved.
This revelation comes from two associate professors in biomedicine from University of Southern Denmark, Søren Hansen and Graham Q. Leslie, who have published this explanation in the latest issue of the scientific periodical Nature [3].
The problem even has been known since 2001.
The substance, which the German biotech company TeGenero ensured could fit like a Lego block in a protein in the six human bodies, did not fit anyway.
But that was what the company claimed in their application to the Brittish medical authorities.

As the original story was a featured news article, this new development should be featured too, if someone can check the original source. (I am not competent to do so myself.)--Niels Ø 09:11, 21 May 2006 (UTC)

Here's the Nature article: [4]. Chl 13:53, 21 May 2006 (UTC)
It's a letter to Nature from 2 Danish academics- not an actual article. Secretlondon 22:42, 21 May 2006 (UTC)
Yes however I still think we should mention it. One of the most interesting bits was not the difference between the human and rhesus monkey CD28 but this bit
"Furthermore, preclinical studies should also include comparative measurements of the binding affinities for both human antigen and primate antigen, to control for unforeseen variations in protein structure.".
I'm still very surprised, as I mentioned a while back (I guess in the archive) that binding affinity tests were not performed. I would have thought they would be basic preclinical tests for any drug and a large difference between the binding affinity of the drug with the target (well preferbly any known targets, perhaps identified via a library screening) between human and animal models would be enough to require serious further investigation.
Nil Einne 13:37, 17 June 2006 (UTC)

[edit] "Elephant man" to loose all fingers on hands and feet

This is terrible: http://www.mirror.co.uk/news/topstories/tm_objectid=17292803%26method=full%26siteid=94762-name_page.html%22 —The preceding unsigned comment was added by 195.70.32.136 (talk • contribs).

http://news.bbc.co.uk/1/hi/health/5121824.stm says parts of three fingers - not all his fingers. Secretlondon 18:09, 27 June 2006 (UTC)

[edit] Could this be misused? In a bigger way?

Other than direct dosing....

Could a virus or a bacteria be developed to spread this?

I don't want this or even suggest that this be pursued. I don't know enough medical technology to know the implications...

Reminds me of some SCI-FI literature "Andromeda Strain" http://www.crichton-official.com/strain/index.html and one of Stephen King's book "The Stand" I think...

Signed curious. —The preceding unsigned comment was added by 70.29.188.133 (talk • contribs).

I'm sure there are more efficent ways to kill people than by inducing a cytokine storm. Issue here is that everybody knew this drug was likely dangerous but they did the tests quickly, makes you wonder if learning something 'else' about the immune system from the tests wasn't the real goal. —The preceding unsigned comment was added by 134.214.102.33 (talk • contribs).

Its useful as a weapon since a cytokine storm leaves many peeople requiring healthcare. Americans might, for example, choose to use sucha weapon while fighting an Islamic countr, such as Iran, since producing thousands of cripple soldiers wouldn't have the same religious impact, i.e. no martyers, big visible costs for fighting, etc. —The preceding unsigned comment was added by 69.61.125.42 (talk • contribs).

Conspiracy theories are great fun - if an organisation claims that they were tests for non-lethal weapons or something then we can add that to the article - but quoting them. Ie - "Political party X stated that it believes that the tests were funded by the United Nations secret anti-Christian warfare department [ref]" Secretlondon 18:32, 1 August 2006 (UTC)

Bacteria lack mechanisms required to make a functional antibody, which is why they are prepared using mammalian cell cultures (usually NS/0 or CHO). I'm sure there is some way you could abuse this compound to do harm but there are far easier ways to harm people and bacteria that naturally make far more deadly compounds than this. —The preceding unsigned comment was added by Austringer (talk • contribs) 12:48, December 11, 2006 (UTC)

Isn't all of this mildly ghoulish? 82.44.64.173

[edit] More information

I just published another editorial on this:

Changing the culture of research

See this week’s BMJ (August 5): http://bmj.bmjjournals.com/

Editorial Further lessons from the TGN1412 tragedy New guidelines call for a change in the culture of research BMJ 2006;333:270-271 (5 August), doi:10.1136/bmj.38929.647662.80

“As eight young men assembled at a London hospital on 13 March this year, they had no idea that within an hour their lives would be changed irrevocably and they would have contributed to a fundamental rethinking of the development and testing of new drugs. The first trial of TeGenero's TGN1412 (a T cell agonist) in humans took place at Parexel's clinical pharmacology research unit at Northwick Park Hospital, London. The events that followed fuelled speculation not only into the conduct of the trial and the nature of the drug, but also into aspects of research as diverse as comparative molecular biology, bioethics, and health economics.

The Medicines and Healthcare Products Regulatory Agency initiated an investigation, but the BMJ and other journals called for a more far reaching inquiry independent of the regulatory agency that had approved the trial. On 5 April the agency released its interim report, and the government announced that an independent Expert Scientific Group, chaired by Professor Gordon Duff, would be appointed "to learn from the Parexel clinical trials incident." On 25 July this group released their interim report and recommendations. …..”

http://bmj.bmjjournals.com/cgi/content/full/333/7562/270?ijkey=whP3FyWKdYWdMvy&keytype=ref

[edit] Dose

The dose given to the men, was just 1/500th the dose that exhibited observable effects in Animals. It is an important point to include in the article. Diamond Dave 14/08/2006 14:05

As has been pointed out before, the dose given to the human volunteers (1/500th of the lowest dose showing effects in animals) contained enough antibody molecules to bind every T cell in the bloodstream ten times over. Neither a mouse nor a monkey is a man; a response (or absence of a response) in animals is no guarantee of the same in humans. 198.140.178.11

Yes, it simply gives a false impression of safety. Diamond Dave 15/08/2006 16:40

[edit] ESG's Final Report

The Expert Scientific Group has issued it's final report. I'm very much a newbie at the whole wikipedia thing so I'm going to let someone more adept do the page edit. Information on the report available here:

[5]

Of interest is the dificulty involved in simulating the cytokine storm in vitro. Austringer 17:00, 11 December 2006 (UTC)

[edit] GA review

A good article has the following attributes.

1. It is well written.

Mechanism of action section does not explain what CD28 actually is and would benefit from a one or two sentence lead summarizing the section for non-specialist readers.

2. It is factually accurate and verifiable.

Has references, however not all refs are in the same format, but this a minor point.

3. It is broad in its coverage.

It covers the subject well.

4. It follows the neutral point of view policy.

I don't think it is biased either for or against the company.

5. It is stable, i.e. it does not change significantly from day to day and is not the subject of ongoing edit wars.

it is stable.

6. It contains images, where possible, to illustrate the topic.

The image Image:T cell activation.jpg might help improve the "Mechanism of action" section.
Actioned —The preceding unsigned comment was added by SeanMack (talk • contribs) 16:18, 2 January 2007 (UTC).

Overall very good, I'll put this on hold until the point in section 1 is dealt with. Drop me a note on my talk page when you're done. TimVickers 00:26, 28 December 2006 (UTC)

I still can't work out from reading the article what CD28 does. Passed the 1 week hold limit so it fails. Sorry.TimVickers 17:34, 2 January 2007 (UTC)
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