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Topic: Catalytic Antibodies and Addiction  (Read 7130 times)

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Catalytic Antibodies and Addiction
« on: March 05, 2007, 06:24:48 PM »
At the risk of sounding too much like a narc, I have picked a controversial subject for my inaugural post on the Chemical Forums Blog.  Before I get underway, I want to thank Mitch for the invitation to contribute here, and I also welcome Maz to the fold.  I’m sure that each of us will highlight very different, but interesting topics.  As for background, I am a grad student in synthetic organic chemistry in the US.

On to the post.  This was inspired by a recent paper by Dickerson and Janda (at Scripps) regarding a catalytic antibody approach to the treatment of addiction (ACS link).  Now I am no chemical biologist, so I admittedly have not followed any of the catalytic antibody literature, but here is my understanding: these antibodies are just like the normal antibodies our bodies produce to fight of infection and the like, except that these antibodies do more than just bind the offending molecule, they catalyze a chemical reaction changing the structure and, hopefully, the bioactivity/degradation of that molecule.  Catalytic antibodies are great for pharmaceutical applications because they avoid many of the toxicology problems that plague non-natural therapeutics.

This is a powerful concept for addiction therapy since, for many drugs, the specific molecule responsible for the intoxicating effect is well known (e.g., LSD, cocaine).  Although this idea is striking, what really caught my eye was the selection of the target in the Dickerson and Janda work: delta9-tetrahydrocannibol (THC).



I love to read the intro paragraphs of papers like this because they always talk about the sweeping socioeconomic effects of whatever particular ailment they are targeting.  As someone who is in a first-world ivory tower academic institution, most of the time the reality of these diseases and effects are at arms-length; they do not directly touch my life.  So this topic really struck me because everybody knows someone who just smokes weed all the time.  Say what you want about the way some people choose to live/waste their lives, I have always thought it is not really my place to judge these people too harshly.  More annoying to me is that a quick search of the Internet will give you a laundry list of reasons why marijuana should not be a controlled substance because, for one reason or another, some people think it just isn’t that bad, some even saying that it is not addictive (One from each side: DEA (pdf file), NORML).  I have read all the arguments for legalizing marijuana, and I have not found one that really convinces me; it is still an intoxicant with demonstrated addictive properties (don’t give me the “so is alcohol” straw-man argument either).

As a scientist, I would really like to see some facts on the matter, and the intro to this paper gives some great scientific data on the subject.  To paraphrase: the now famous “cannabis gateway hypothesis” does, in fact, have some real experiments that show that delta9-THC specifically changes opiod receptors in the body, perhaps making them more susceptible to other drugs (link to that study).  Not proof positive, but a start that is not just based on surveys and statistical manipulation.  To summarize the results in the paper, Dickerson and Janda have identified catalytic antibodies which do effect oxidative degradation of delta9-THC, mostly to cannabitriol (which is not the predominant metabolite in humans).  Some detailed kinetic studies suggest that these antibodies may drop the effective half-life of delta9-THC from ~20 hours to less than 40 minutes.  They have some preliminary biological data on the effect of cannabitriol (which incidentally is also a naturally occurring compound in cannabis) but they need some more extensive studies to shore up the efficacy of this approach in reality.



I guess my point is that while at one end of the spectrum pervasive drug use has slowly become a more acceptable part of our society, I am very happy to see that there are prominent scientists looking to address these problems as they would any other ailment.  Kudos to these researchers for taking on an unpopular problem.

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« Last Edit: May 09, 2007, 12:19:05 AM by Mitch »

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Re: Catalytic Antibodies and Addiction
« Reply #1 on: March 05, 2007, 09:16:44 PM »
I'm more of the, allow Marijuana for medical use. No reason not to let cancer patients get high, if it makes them feel better.
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Re: Catalytic Antibodies and Addiction
« Reply #2 on: March 06, 2007, 12:32:42 AM »
I kind of intentionally avoided the medicinal marijuana argument.  I have always thought of those laws as an end-run, especially since there are alternatives like Marinol.  That's a controversial topic too though.

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Re: Catalytic Antibodies and Addiction
« Reply #3 on: March 06, 2007, 09:47:37 AM »
I read a paper revolving around a Morphine metabolising Abzyme last year. One of the major problems with Abzyme seems to be the binding and catalysis rates, which are still very low. I don't know how far protein engineering has improved the situation yet, but I suppose it's quite a tricky topic with a lot of modelling work (yuck, computational biology). The initial design is intruiging, as it involves the synthesis of a transition-state analog for the sought reaction and endless screenings for an AB that actually binds the educts at a reasonable rate as well as catalyses the reaction within a life-time (bless phage display techniques).
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