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Biotech Science

Drugs to Prevent Cell Suicide 110

MrErlenmeyer writes "Many injuries and diseases including heart attacks, stroke, and Parkinson's cause healthy cells to kill themselves. A group of scientists at Washington University in Saint Louis believe they have a lead on how to stop apoptosis (unwanted cell suicide) and thus minimize the tissue damage that occurs as a result of these injuries. They designed drugs that halt the actions of executioner caspases, proteins that act as a molecular wrecking crew. Other scientists had found that a chemical called isatin could prevent tissue damage in rabbit hearts that were deprived of oxygen. This was the starting point for the team of researchers in Missouri. By making some changes to the molecule, they were able to develop an even more effective molecule. With some further refinement, this may lead to a new class of emergency medications."
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Drugs to Prevent Cell Suicide

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  • Cancer (Score:2, Interesting)

    by Anonymous Coward
    Since cancer is uncontrolled cell growth, has increased risk for cancer been looked at?
    • Re:Cancer (Score:4, Interesting)

      by NeverVotedBush ( 1041088 ) on Friday June 29, 2007 @03:39PM (#19693839)
      I immediately thought the same thing. There is an article in the New Scientific American about how cancer cells modify their environment so that the processes that kill off cells are inhibited. This new treatment could lead to similar. On the other hand, would you rather be dead or brain dead or increase the chance you get cancer?

      This could also be a clue in how to treat and kill off cancer cells.

      Interesting stuff.
      • Considering that this is a transient treatment, the problem with cancer will probably depend on the length of the treatment, which probably would not lead to a very large increase in cancer rates. There is still a lot of ground to cover for cancerous cells to become malignant (angiogenesis, telomere limits) and these sorts of things take decades of accumulated mutation and selection.

        A three month suppression of apoptosis and then a return to homeostasis is probably safer than a three month vacation to Haw
    • by enjerth ( 892959 )
      While that's an interesting question, I don't think it should be a consideration for suppressing or delaying the production of the drug.

      If it comes to it, I'd rather die from cancer 5 years after a heart attack rather than die from the same heart attack.
    • During the time of your treatment, numerous almost-cancer cells get to be cancer cells.

      You're not going to keep taking this drug, are you? Take it once, it wears off... that's not a lot of time for nasty things to grow.
  • by smellsofbikes ( 890263 ) on Friday June 29, 2007 @03:30PM (#19693725) Journal
    Cessation of programmed cell death is often called cancer.
    I'm sure they have all sorts of good research and know lots about this, and I freely grant that a 10x increase in your chances of getting cancer somewhere down the line beats Parkinson's, but this still sounds really scary.
    • by nonsequitor ( 893813 ) on Friday June 29, 2007 @03:40PM (#19693863)
      This is for emergency response to strokes, heart attack, etc to prevent healthy cells from being destroyed by the enzymes which cause apoptosis. It would follow common sense that the inhibitor would be out of the system within a day or so after treatment with the drug is ended. In conclusion, RTFA.
      • by nten ( 709128 )
        A previous story indicated that apoptosis was responsible for the tissue damage caused when blood oxygenation was resumed, even up to several hours after the cessation of breathing and brain activity. If this drug could be spread to all tissues (including brain), we might be in for some Herbert West style fun.
      • I guess it's pretty fucking useless against Parkinson's then isn't it?
        • It is not yet a treatment, only experimental compound used on lab animals. As is, if the compound were modified and approved for use on humans it would not be immediately useful against Parkinson's. Eventually what is learned by further studying the processes involved the article asserts it may one day lead to treatments for Parkinson's.
    • Yes, "unwanted cell death" is inaccurate. Apoptosis has a function for survival (mustn't it, in order to exist in life as prevalently as it does?)
      • by smellsofbikes ( 890263 ) on Friday June 29, 2007 @04:03PM (#19694157) Journal
        Your fingers are formed by apoptosis, in fact. Well, so is most everything: it all grows as tissue, and programmed cell death is what allows tissues to separate. (One interesting area of research is how the body forms hormone concentration gradients that rsult in regional apoptosis, leading to formation of eg fingers from continuous tissue.) But of course that's way prior to birth. Once you're born, having injured or marked cells commit suicide is, generally speaking, a very good thing, and messing with their ability to do so has some interesting implications.
      • by catbutt ( 469582 )
        They probably should have said "unwanted cell death" was the definition of "unwanted apoptosis". Since what they are talking about is stopping the sort of apoptosis that is problematic.

        (mustn't it, in order to exist in life as prevalently as it does?)
        Not necessarily. Cancer is prevalent, but it is not a function for survival. Well, not survival of the host anyway.
        • Indeed, evolution favours advantages by selecting against disadvantages. If there is no disadvantage there is no reason for it to disappear.
    • by Trifthen ( 40989 )
      It would only be temporary.

      The problem is, when a cell is deprived of oxygen, it gets marked for death as soon as it's reactivated. Hence, perfectly salvageable tissue, some that can't be replaced easily like heart muscle, dies merely as an inherent precaution.

      Now, I don't know about you... but I'd rather have a slight increased risk of cancer somewhere down the line, than be dead now thanks to my body's overzealous attempt to keep me healthy.

      This is a Good Thing (tm).
    • Re: (Score:3, Insightful)

      by Manchot ( 847225 )
      Of course, TFA also mentions that this method allows researchers to study apoptosis further, by allowing them to observe individual cells undergoing the process. Conceivably, once the mechanisms of the process are understood better, it will eventually be possible to trigger apoptosis in malignant cells (i.e., curing cancer). This development could possibly have revolutionary implications in the realm of cancer treatment.
  • by Anonymous Coward on Friday June 29, 2007 @03:30PM (#19693733)
    As stated in the second paragraph of the article, apoptosis is simply the process of cell death--a something perfectly normal and required by the body. Hardly "unwanted"! See http://en.wikipedia.org/wiki/Apoptosis [wikipedia.org]
    • Re: (Score:2, Insightful)

      by F-3582 ( 996772 )
      Man, but I'd love to have some webs between my fingers! Or a few billions more brain cells... Or a bazillion T-Lymphocytes trying to kill me... On the other hand, such medication would indeed be great for all those people who were cut off from oxygen for too long and whose myocard cells usually go into apoptosis once they're re-oxygenated.
    • Re: (Score:2, Insightful)

      by Trifthen ( 40989 )
      I disagree.

      When I've just had a heart attack, and apoptosis would rather kill 40% of my heart tissue, thereby killing me outright, than possibly increase my cancer risk, it's most certainly unwanted.

      For emergency purposes, stopping apoptosis is perfectly valid, and in fact desired to the grim alternative. I'd assume that once the treatment is out of your system, apoptosis is no longer suppressed, and everything goes back to normal... well, after a triple bypass to avoid future heart-attacks due to clogged
    • It is unwanted in cases like ALS. A French company called Trophos also works on this problem. [trophos.com]
  • Apoptosis (Score:5, Informative)

    by HomelessInLaJolla ( 1026842 ) <sab93badger@yahoo.com> on Friday June 29, 2007 @03:33PM (#19693767) Homepage Journal
    The summary characterizes apoptosis as unwanted cell suicide which, in most cases, it most certainly is not. Apoptosis is one of the natural mechanisms by which the body eliminates cells which have become damaged, dysfunctional, or are simply no longer needed.

    Especially with respect to cancer research apoptosis is a pathway which we seek to activate. Cells which become cancerous are supposed to enter apoptotic cycles and prevent themselves from creating tumors within the tissue. Cancerous cells manage to win the race condition between apoptotic and survival pathways but, in terms of the mechanisms at work within the cell, are tottering on the edge. Many new cancer treatments rely on this on the edge circumstance in the interest of introducing a pharmacologically active substance into the body which will cause cancerous cells, on the edge of apoptosis, to move fully into apoptotic function.

    Since the cells in the body are constantly in a state of self-regulation and interregulation it is possible that cells which enter apoptosis too easily are similarly causes of diseases. It is this set of conditions that the researchers in the article wish to treat.

    Don't be misled about what apoptosis actually is, though, or be swayed to view it as good or bad. Different conditions within the tissue call for different actions within the cells which make up that tissue.
  • by elrous0 ( 869638 ) * on Friday June 29, 2007 @03:35PM (#19693783)
    Most suicide attempts are cries for help, you know.
  • by drsquare ( 530038 ) on Friday June 29, 2007 @03:36PM (#19693805)
    Why would you want to stop prisoners killing themselves? It would save tax-payers millions, and would be a much more effective form of justice than today's "OK you ran over a granny whilst drunk and stoned off your head on your way back from a bank robbery, you're sentenced to six months with sky TV, pool table and gym, out in two months due to good behaviour, plus free benefits if you can't be bothered working" form of justice that is doled out today, in Britain at least.
    • When I saw the headline, I thought "Wha? Somehow they've come up with drugs that target depressed prisoners?" Then I RTF summary and, eventually, RTFA. Parent's pretty funny. Though I could have done it better.
    • Yeah, I work in Law Enforcement. In true Slashdot fashion, I read the headline and formed an opinion. Drug prisoners? Okay, if it keeps them from offing themselves. Being interested, I read further... apoptosis? Damn, I didn't realize there was a word for it. Unwanted cell suicide? Aren't they all? Well, most of them anyway. I really need to start reading the articles.
    • I did 5 years Fed time in Texarkana TX and I can tell you that it ain't no picnic. The problem with American justice is that rapist, murders and child molesters get very little time.. except murder.. we've got life or good old capital punishment for that... and someone getting busted with 100 pounds of pot get's 10 years. There was one guy that I remember that mailed 10 hits of acid in the mail which made it a federal crime and he got a mandatory minimum 10 years. I'm convinced that really there is only the
    • I know this thread has nothing to do with prisoners and suicide, but I could not resist responding to that comment. I actually saw several people commit suicide while I was in there, and guards who moved slow as syrup when a guy had a heart attack and I thanking god that I did not have any health problems.
  • Boy, this has got "Unintended Consequences" written all over it. Seriously, I hope that this works brilliantly and the thousands of sufferers of Parkinson's disease etc. are able to be helped by this, but it seems like it could be a very shiny wrapper around an all new Pandora's box.
  • I am probably going to get Alzheimer's disease (my grandfather had it, and it skips a generation). Insight prevention/treatment of it happens slowly. I hope this is different.
    • by stox ( 131684 )
      You may be lucky, it looks like relief is on the way for Alzheimer's patients. Bapineuzmab is about to enter phase III trials. It is an anti-body which attacks beta-amyloid which is thought to be the cause of Alzheimer's. Entering phase II trials is a vaccine which also attack beta-amyloid. Both are being produced by an Irish pharmaceutical company, Elan, is partnership with Wyeth.
  • by Anonymous Coward
    Apoptosis is a natural cell mechanism, and one of our bigger problems (cancer) is caused when cells _fail_ to commit suicide.

    I suppose apoptosis-preventing drugs might have their place, but don't smoke or try to get a tan while you're taking them.
    • First understand how to block it where you don't want it, and that could perhaps help to understand how to stimulate it where you want it. This could be the start of a new-new line of CANCER drugs, maybea a general cure.
  • Your body currently has a bunch of cancerous cells here and there throughout. But you'll probably live a long, healthy life, and never be diagnosed with cancer. Why? Because apoptosis (among other cell processes) helps kill the cells that are off-track and FUBARed.

    This technique better be applied very specifically to cells and not "generally" to a mass of tissue, otherwise you'll be making the equivalent of a petri dish (read: idealized growing environment) for cancer.
    • But you'll probably live a long, healthy life, and never be diagnosed with cancer.
      Not sure about the latest numbers, but the risk of getting cancer as a male used to be about 50%. Of course, a healthy lifestyle, ... ,etc will put the odds in your favor.
  • :side effect may include nausea, vomiting, and super cancer:
  • A pill to prevent cell suicide? Like in jail? Reminds me of the time I was arrested for littering. It was two Thanksgivings ago, that is, two years ago on Thanksgiving...

    The cop took me to the jail, he says, "Kid, I'm gonna put you in the cell, I need your wallet and your belt."

    I says, "I understand you want my wallet so I don't have any money to spend in the cell, but why do you need my belt?"

    He says, "kid, we don't want any hangings." Of course, he was just making sure, because he also took out

    • Reminds me of the time I was arrested for littering....
      ....The cop took me to the jail, he says, "Kid, I'm gonna put you in the cell....

      Jail? for littering?

      Excuse the off topic-comment, but what did you toss casually out the car window, a metric ton of toxic waste?
    • by TheLink ( 130905 )
      But why did he have to take out the toilet seat? Shouldn't it then have been permanently removed?
  • I saw the subject and thought that they'ed invented a drug to prevent prisoners to stop commiting suicide. Then i read a sentence or two further and saw that how off base I was. Never the less, i'll comment about it.
  • by Pitr ( 33016 )
    A bit offtopic but, did anyone else think this sounds like a plot device for a zombie movie?
    • by geekoid ( 135745 )
      Yes..but then I think that of every story sounds like a plot device for a Zombie movies....

  • by Pedrito ( 94783 ) on Friday June 29, 2007 @04:53PM (#19694673)
    First of all, this doesn't seem like a huge deal. By the time you get to the hospital, most of the cells that are going to die are already undergoing apoptosis (BTW, that's programmed cell death and not necessarily unwanted cell death). The other issue is that hypoxia also causes cell necrosis, which is another form of cell death that's completely different from apoptosis and wouldn't be saved by this kind of drug.

    The major issue, however, is simply that most of the cells that are going to die are irreparably damaged byt he time you get to the hospital. They ER will likely give you drug thinners and do whatever else is needed to get oxygen supply back. Not that this drug wouldn't be somewhat helpful, but I'd be really surprised if there's any great improvement in the % of lives saved. And any life saved is certainly worth the effort, but I just don't see this as a major breakthrough.

    Now, show me a drug that can selectively induce apoptosis in certain cells, and then we'd have a cure for most forms of cancer (most forms of cancer are the result of cells whose apoptosis pathway is failing for some reason), and that would be a big deal.
    • They are probably thinking about a nitroglycerin or epinephrine type prescription where high risk patients carry it with them so they can take it immediately if the shit hits the fan.
    • Re: (Score:3, Informative)

      by compro01 ( 777531 )
      as far as i understand it, after a certain time of no oxygen, a "suicide bit" gets set and once oxygen comes back, the cell dies, but not until then.

      this would prevent that. the cells might not work for long, but hopefully long enough for replacements to come in, as a sizable number of cells spontaneously dying in the heart or brain tends to lead to death for everything else, but a few cells dying at a time and being replaced wouldn't, which i presume is the intent.

      though i can't RTFA (the server is probab
      • Actually, the current hypothesis is that the apoptosis in hypoxia (drowning, heart attack, stroke) is triggered because the rush of fresh oxygen overwhelms what the cell is capable of dealing with, poisoning the cell and irreparably damaging the DNA.

        Oxygen is a poison, as you may or may not know. Our cells can only use it because they create various enzymes, such as superoxide dismutase [wikipedia.org], that clean up the mess made by stray oxygen before it can do too much damage. Take away those enzymes, and oxygen rad

  • Reperfusion (Score:4, Insightful)

    by Anti_Climax ( 447121 ) on Friday June 29, 2007 @04:54PM (#19694679)
    They should probably have a related reading link for the story posted in May [slashdot.org] regarding the discovered consequences of oxygen reperfusion [msn.com] in the human body.

    Quick summary: Doctors and scientists are finding that the cells of the heart and brain are still alive after clinical death, but they go into a dormant state. Jolting them back with oxygen and adrenaline after 4-5 minutes seems to kill the otherwise still living cells. A trial run on 34 cardiac patients indicates a significant increase in CPR success when done in a very gradual and controlled manner after that 4-5 minute mark (about 80% success opposed to around 15% for traditional CPR techniques)
  • Drugs ? Emergency Medication? Over here!
  • Think of the applications for drowning victims too. Especially here in Canada where in the winter you're not dead till you're warm and dead. Now there's a chance that if they flood you with this stuff and get you to a local hospital there's a good chance of no/less brain or heart damage.
  • Apoptosis is not "unwanted cell suicide". Apoptosis is an essential part of growth and maintenance of organisms. Without apoptosis, your body would be a lump of flesh. If you simply turned off apoptosis in adulthood, your immune system would go haywire, viruses would proliferate, and so would cancer cells.

    Some specific forms of apopotosis may be harmful in some cases, but that's rare.
  • Think and read before replying -- apoptosis is, under normal circumstances, a good thing. The whole reason it says "emergency medication" is because that's the type of medication this knowledge would be used for. When cells don't get oxygen for whatever reason (let's say, pulmonary or cardiac failure of some sort), they start to die off. So you'd inject them with some of this if you couldn't get their heart started in time to prevent cell death, or in a similar situation. Seriously, haven't you people e
  • Linky [msn.com]

    In short, just because your heart stops beating doesn't mean your cells are going to die anytime soon. Cells are undergoing (committing?) apoptosis when oxygen is reintroduced, after they have been deprived for 5 minutes or so.

    If we could prevent apoptosis, we could conceivably restore life to a person who has been dead for hours. I wonder if that could time could be stretched even further under cold temperatures.

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