Tuesday, March 21, 2006

A small lesson for alternative medicine in the TGN1412 tragedy

By now, you've probably already heard about the young, previously healthy British volunteers for a Phase I clinical trial now fighting for their lives after receiving a monoclonal antibody therapeutic, TeGenero's TGN1412. New Scientist has a concise overview, but I also refer you to Insider at PharmaGossip Derek Lowe's In the Pipeline and Anthony Cox's excellent Blacktriangle for viewpoints from three different disciplines.

Fiddling with the immune system is tricky business, and even highly experienced scientists are having difficulties understanding the intended use of TGN1412 in autoimmune disorders like rheumatoid arthritis and "cancer-related immune deficiencies" [from TeGenero's website].

As I understand it, the antibody therapeutic was designed to bind the CD28 receptor on regulatory T cells and act as a superagonist, overriding the body's normal requirement for a second, antigen-specific signal to activate the T cells. This nonspecific, super "immune boosting" effect (ever heard of that term before?) has now put two of six volunteers into multiple organ failure.

I'm reminded of the "immune system boosting" claims of many alternative therapy hucksters. Even if such a remedy existed, the immune system is far too complex to regulate with a single, myopic approach due to its multiple checks and balances, feedback loops, and other regulatory process that normally keep us from attacking our own tissue while recognizing and mounting responses against invading organisms. Even the most clever cancer immunologists have only made incremental headway in harnessing immune responses to treat cancer.

However, alternative therapy advocates prey on the public's misunderstanding of the immune system - it's a struggle for many scientists to understand, just like how homeopaths throw around terms from quantum physics. I'm reminded of my brush with fame on an AM radio talk show a few years ago where a woman who was taking Echinacea noted that her rheumatoid arthritis got worse everyone she took the herb. My simple response was that even if Echinacea was "immune boosting," the non-specific release of cytokines could make autoimmune disorders like RA much worse. (Recent data are indeed suggestive that some Echinacea compounds may indeed have potent immunomodulatory effects.). The same goes for asthma and why I always worry about folks using Echinacea supplements whose asthma has a strong immmune component. Fortunately, most Echinacea products on the market are of such inferior quality that they only occasionally pose a threat.

But the next time some CAM huckster tries to sell you a remedy that will "boost your immune system," ask them how they can be certain you won't end up in the hospital like the unfortunate Phase I volunteers in London.


At Tue Mar 21, 09:14:00 PM EST, Blogger Bronze Dog said...

Nicely done.

At Wed Mar 22, 01:39:00 AM EST, Blogger define_me said...

I find that Echinacea is overrated and overused. Many consumers don't even know that only one of the three species is technically considered to be "immune boosting" and the worst part is that stores do not differentiate them. It also has a horrible smell. Yuk!

At Thu Mar 23, 12:51:00 AM EST, Blogger Impatient Patient said...

I use Cold FX which is a ginseng extract that boosts immunity. I wonder about how this modulates my immune system, and what if any cytokines are being ramped up. If someone has MS or Lupus should they use it? Those questions always race in my mind.

I personally think that sometimes a good old fashioned hot toddy, a hot shower and a really good sleep help a lot. But----- using Cold FX as directed has seemed to work to change the severity of a cold that STARTS in my chest.

I used to think I was the only one who thought about this stuff... I am so glad I am not- LOL!

At Fri Mar 24, 08:53:00 AM EST, Blogger luna_the_cat said...

Thanks for an excellent post on this. I guess I would just like to add a comment to something you've said here:

"However, alternative therapy advocates prey on the public's misunderstanding of the immune system..."

This is true. But let's not discount how the members of the public respond. First, there is a strong anti-intellectual movement (or as one blogger has put, an anti-expertise movement) in many places, linked to a lack of science education and the kind of feel-good romanticism which puts strong value on "traditional", "natural", "ancient wisdom" keywords. And in many cases, there is an additional desperation. It is absolutely natural, and understandable, for people who have not been cured or even adequately helped by allopathic, evidence-based medicine to look elsewhere. I have a personal interest in that kind of phenomenon; my mother has had severe rheumatoid arthritis from the age of 36, and the level of crippling pain that she lives with contstantly now has driven her to poison herself several times with first one, then another, "miracle cure" which she has seen advertised in a magazine or the latest pop-health-fad book. And I can't condemn her for that, because simply of the level of pain I know she is in.

There is a point to all this, honest. The point is that I think that conventional medicine needs to address its marketing. For the most part the only marketing I've seen has been the "Ask your doctor if [fill-in-the-blank] is right for you (may have the following side effects....)" ads on TV. Frankly, I despise those. Aside from encouraging people to ask for stuff they don't need and probably shouldn't have, and using advertising to make an end run around medical judgement, they also encourage the perception that people ought to be able to take a pill and have whatever is wrong with them instantly fixed.

What conventional medicine needs is more honesty, but also, a more comprehensive address to show people the benefits of evidence-based medicine. A few magazine ads. A few infomercials. Not ones selling anything in particular, but just selling the concepts. It may not be as financially rewarding for the drug companies, but even though it could never be 100% effective it would probably do some good.

Luna (who enjoys banging her head off brick walls, and who followed you over here from Respectful Insolence).

At Thu Apr 06, 04:48:00 AM EDT, Anonymous BOB FIDDAMAN said...

MHRA - In whose Interests?

The recent TeGenero drug trial debacle was an accident waiting to happen. As long as the Pharmaceutical Industry continues to suppress clinical trial data the MHRA (Medicines and Healthcare products Regulatory Agency) will walk blindly and feed the British public false information.

News this week that GlaxoSmithKline knowingly withheld clinical trial data from the MHRA regarding the top selling anti-depressant drug Seroxat will add further fuel to the fire and hopefully push for an independent review into how the MHRA could be duped into believing that a drug they have reviewed on numerous occasions was safe.

The MHRA are made up of medical experts, some of whom are former employees and shareholders of the pharmaceutical companies they grant licenses to. Surely this is wrong and at the very least there is the suspicion of a conflict of interest?

For too long now the MHRA have been hoodwinked by the Pharmaceutical Industry. Lawsuits for damages in respect of harm caused to patients are popping up all over the place, but avoid media and public scrutiny because they are usually settled out of court on the proviso that evidence is not made public.

A public enquiry is needed to examine how the MHRA is run and why former Pharmaceutical Industry directors are allowed onto the board. Would a convicted drink driver be allowed to adjudicate on a road safety panel?

The MHRA need to pull the plug NOW on their close associations with the Pharmaceutical Industry. The British public expects and naively assumes impartiality and not a regulatory authority whose main interest seems to be one of ‘delivering jobs for the boys.’

Mr Robert Fiddaman (Group Moderator of the Online Seroxat Support Group)

Birmingham, UK

At Sat Jul 08, 02:12:00 PM EDT, Anonymous Anonymous said...

Exactly. The problem is not with medicine (alopathic or otherwise).
The problem is of corruption.
And the UK drug regulatory body, the MHRA is as corrupt and conflicted and useless as you get.

At Tue Aug 08, 12:52:00 AM EDT, Blogger john grant said...

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