GMO corn for LSD

Since the anti-science foo-foo hippies lost their bid to have all foods labeled ‘CONTAINS GMO WARBLEGARBLE! TEACH THE CONTROVERSY!’, a group of scientists at the Evil League of Evil have generated GMO corn for LSD. I guess as a gesture of good-will, or something.

There.

I hope everyones happy now.

*whisperswhisperswhispers*

What?

*whisperswhisperswhispers*

The GMO corn for ‘LSD’ is not for the mind-altering drug ‘LSD’, but actually a putative treatment option for ‘Lysosomal storage diseases‘?  This is GMO corn that could help treat a collection of genetic conditions that kill children/debilitate adults?

Oh thats much cooler!!

Production of α-L-iduronidase in maize for the potential treatment of a human lysosomal storage disease

People with a lysosomal storage disease have… something ‘wrong’ with their lysosomes.  When your cells cannot break down waste/old proteins/etc properly, all that garbage builds up, and terrible things happen.  You might have heard of Tay–Sachs disease (‘common’ in European Jewish populations), or Niemann–Pick disease.  Usually these kinds of diseases arise from non-functional or disfunctional enzymes (proteins that *do* something, have an active ‘job’).

Thus some of these diseases can be treated with enzyme replacement therapy… to the tune of $300,000-$800,000 per year.

:-/

Why the hell is this treatment so expensive? I mean people with Type I diabetes also need a constant infusion of a protein, insulin, and they only cost maybe a couple thousand bucks to treat a year.  Why $800,000???

Because enzymes are hard to produce cheaply.

One way we cut costs is to grow needed proteins in bacteria, blow up the bacteria, harvest the protein.  We cant do that with enzymes humans need, though, because in order for the enzyme to work properly and not illicit an immune response, it needs to be decorated properly.  With sugar.  And bacteria dont use the same sugars human use.  Our immune system uses this fact to fight bacteria.

We also cant get plants/plant cell lines to make the enzymes for us– They have sugars humans dont have too– xylose and fucose.

So scientists have been working really hard trying to figure out a way to grow the necessary enzymes in bacteria/plants that keep the ‘bad’ sugars from being added– but they all require modifying the enzyme in some way.  Too many modifications, and you risk generating an immune response to the enzyme when you try to administer it to patients.

This group of scientists were very, very clever.

A lot of the sugar ‘decorations’ are changed in a cells Golgi.  So, an enzyme being made in a plant cell in the endoplasmic reticulum, and the same enzyme being made in a mammalian cell in the endoplasmic reticulum, look pretty much the same.  But when those same proteins are trafficked to the Golgi, the plant enzyme gets xylose and fucose decorations, and the mammalian enzyme gets galactose and sialic acid decorations.

They noticed that a protein in plants, γ-Zein, is made in the ER, and then goes about its business.  It doesnt get shuffled over to the Golgi.  And this is the result of the mRNA that makes γ-Zein, NOT a feature of the γ-Zein protein itself.

Which means that they could, theoretically, put the γ-Zein “GO TO THE ER AND THEN DO NOOOOT GO TO THE GOLGI!!!” message on an enzyme we want to make for and LSD, and maybe we could get the plants to make a human-useable enzyme, without altering the protein in any way!

They tried it with one of the enzymes used to treat MPS Iα-L-iduronidase. They generated a GMO corn that would make human α-L-iduronidase with the corn γ-Zein mRNA signals to make sure it stayed in the ER and didnt get ‘decorated’ in the Golgi.

And it worked!

The corn made ‘good’ human α-L-iduronidase!  The right sugar on the outside, it appeared to be biologically active (even though they didnt test it in any animal models or anything, just in lab experiments).  There was some contamination by α-L-iduronidase with ‘bad’ sugars– the mRNA signal was not able to keep ALL of the protein out of the Golgi– but it was easy enough to clean up the protein by filtering out any of it that ‘stuck’ to anti-xylose or fucose purification schemes.

And again, none of this has made it into humans yet.  And, just to be clear, its not like LSD patients will be able to eat corn instead of getting IV infusions of functioning enzymes.

What this study is, is showing that there might be a cheaper, safer (dont have to worry about human pathogens contaminating a corn field!) way of treating a family of genetic diseases.

GMO corn.

Comments

  1. #1 Scented Nectar
    November 8, 2012

    I grew up near a kid with Tay Sachs. Even though he lived much longer than they expected (to 17), his body was a crippled mess, and I doubt he enjoyed life much. If he had had “GMO” enzymes back then, he might have had a full and normal life. These enzymes are going to prevent a lot of suffering.

    Oh, almost forgot. Some hippies asked me to ask you…
    “Hey man, if we stop freaking out about GMO plants/food, will you make the other LSD your next project?” :D

    http://www.youtube.com/watch?v=J39fAJT8Ua4

  2. #2 Matthew Herper
    November 8, 2012

    Enzyme replacement therapy isn’t expensive mainly because of the cost of production, but because of the small patient population. All “ultra-orphan” drugs are in this price point. Cheaper methods of manufacture only bring down the price a bit, not a lot.

  3. #3 Phil Giordana FCD
    November 9, 2012

    Oh fuck! And here I was hoping for some trippy corn kernels, 70′s style. FUCK YOU SCIENCE AND YER STUPID INITIALS!!!

    Otherwise, pretty cool.

  4. #4 dinkum
    United States
    November 9, 2012

    That Scientific American article in the first link is a virtual syllabus for the foo-foos (nice one) to get their shit together and make themselves worth taking seriously. Too bad so many of the commentors didn’t read for comprehension.

    Basically, separate the science from the business practices, and then actually learn something about the science. Address the specific problems. Then you won’t be so much of an obvious dumbass for railing against, say, treatments for genetic diseases.

    Didja read the actual proposition? Bunch of vague fearmongering can, could, may, might crap with no references to anything resembling evidential support, and a healthy schmear of corporate conspiracy (it’s just the money trail, people, no conspiracy needed). Even the major Cali newspapers saw through it.

    It’s funny that “the right to know” never seems to include “the right to actually know what you’re talking about.”

  5. #5 B Griffin
    Florida
    November 9, 2012

    @DINKUM:
    When you wrote:
    .
    ‘…Too bad so many of the commentors didn’t read for comprehension…..’
    .
    and then:
    .
    ‘….. Then you won’t be so much of an obvious dumbass for railing against, say, treatments for genetic diseases…..’
    .
    To whom are you referring? The relevant-to-topic nature of other three comments at the time of this posting clearly demonstrate no significant deficit in reading comprehension of what was posted.
    .
    Who is ‘railing against’ treatments for genetic diseases?
    .
    It is difficult to know exactly where the breakdown has occurred, so the following suggestion will necessarily be overly broad…..
    .
    …When suggesting shortcomings in others, such as a deficiency in reading comprehension, it is probably a good idea to do a quick personal review to make sure you aren’t the pot calling the kettle black;
    ….. reread that to which you are responding (with accusations of deficiencies)..to make sure you are responding to something that was actually intended;
    ….any plea for others to ‘read for comprehension’,should be composed in a style that might fairly be described as ‘written for comprehension’

  6. #6 dinkum
    November 10, 2012

    @B Griffin

    Well, as my comment began with,

    “That Scientific American article in the first link,”

    I thought it was fairly clear that I was referring to the Scientific American article referenced by the first link in Abbie’s OP (‘foo-foo” being another reference point), and that the immediately following sentence regarding commentors would clearly be referring to the commentors on that article.

    Perhaps I should have typed the words, “on that article” between the phrases ‘Too bad so many of the commentors” and, “didn’t read for comprehension,” but as I clearly stated my thesis in my first sentence, I did not, at the time, consider contextual continuity through a two-sentence paragraph to be an issue.

    My apologies. Too much (bad) fiction writing of late, I suppose.

    My point was that the aforementioned Scientific American article, linked to in the first sentence of Abbie’s original post under ‘anti-science foo-foo hippies lost their bid,” in colored font, is a thesis statement on how the anti-GMO crowd can restructure their positions for effective legislative change, if that is actually their goal. The rest was my burbling on why I thought so, still referencing the Scientific American link and the comments thereon.

    You can have your lecture back. I have more than I can use already, and I would have been more than happy to clarify without it.

  7. #7 martin
    November 11, 2012

    It may be interesting to note that plant cell-derived glycoprotein is already in use for treatment. Israeli company Protalix makes recombinant human glucocerebrosidase (for treatment of patients with another lysosomal disorder, Gaucher disease), which is produced in carrot cells and contains one extra fucose residue in its oligosaccharide chains (compared to its human counterpart). Surprisingly, this does not significantly increase its imunogenicity in humans. Carrot cells are grown in supension in polyethylene bags and glucocerebrosidase is targeted to the storage vacuoles, using a plant-specific C-terminal sorting signal, which is a neat trick, because the oligosaccharides remain high mannose – therapeutic glucocerebrosidase is targeted to macrophages via mannose receptor. Nice technology, too.

  8. #8 Josh
    November 19, 2012

    Hm, I have been occasionally reading your blog for some time now, ERV (the only blog on scienceblogs.com I bother with after the pepsi thing) and I am disappointed at your failure to understand the situation here.

    I suggest you check out foodpolitics.org if you want to get the viewpoint of a reliable, non hippy type regarding GMO labelling. They actually should be labelled, and you reveal your gullibility by taking the other side.