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Researchers Neutralize Parkinson's Dopamine Killers 105

Posted by ScuttleMonkey
from the knowing-is-half-the-battle dept.
futurity.org writes with news that Iowa State researchers have made a breakthrough that could eventually lead to a cure for Parkinson's. Identifying the protein that kills the dopamine-producing cells in the brain has allowed the researchers to disable it and could be the first step in the development of new treatments. "Now, Kanthasamy’s group is looking for additional compounds that also can serve to neutralize protein kinase-C. By identifying more compounds that perform the function of neutralizing kinase-C, researchers are more likely to locate one that works well and has few side effects. This discovery is expected to provide new treatment options to stop the progression of the disease or even cure it. 'Once we find the compound, we need to make sure it’s safe. If everything goes well, it could take about 10 years, and then we might be able to see something that will truly make a difference in the lives of people with this disorder,' says Kanthasamy."
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Researchers Neutralize Parkinson's Dopamine Killers

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  • by killmenow (184444) on Monday November 09, 2009 @03:05PM (#30037300)

    This research seems kinda shaky.

    • by tool462 (677306)

      The insensitivity of this joke made me shudder.

    • by noundi (1044080)

      This research seems kinda shaky.

      That's not funny.

    • by makuabob (1035076)
      Seems a bit off-color for humor, but...

      This is GOOD news! When it pans out, I have relatives who will be better.
      C'mon! Lighten up, be happy!

    • by physburn (1095481)
      Its was shaky but stiffened up nice at the end. Serious Parkinson's diease is a killer, one of the slow degenerative ones, that destroys the brain of it victim so any hope for a cure is good. Ten years is to long.

      ---

      Drug Discovery [feeddistiller.com] Feed @ Feed Distiller [feeddistiller.com]

  • Wouldn't it be nice if this were NOT vapor? I'd like to see Michael J. Fox [wikipedia.org] be able to stay around as long as possible.

    Here's to hoping this pans out. Cheers.

  • by afidel (530433) on Monday November 09, 2009 @03:10PM (#30037370)
    Since the disease leads to paralysis then death how safe does it have to be to be effective? If the cure kills 5% of the people that take it I would think that will be less than the 10 year delay in getting a "perfect" cure out of the lab and through FDA testing.
    • Re: (Score:2, Insightful)

      by jrmcc (703725)
      If I am looking at a slow decline into the symptoms of Parkinsons and a nasty end, would I take a 95% shot at stopping the symptoms versus dying?

      I'll take the meds!!

    • by ColdWetDog (752185) on Monday November 09, 2009 @03:21PM (#30037552) Homepage

      Since the disease leads to paralysis then death how safe does it have to be to be effective? If the cure kills 5% of the people that take it I would think that will be less than the 10 year delay in getting a "perfect" cure out of the lab and through FDA testing.

      Firstly, there are drugs that are moderately effective in Parkinson's Disease - not curative, but they do significantly improve patient functioning. Secondly, and most importantly, they found enzyme that they affects dopamine levels. They HAVE NOT (at least as far as I can tell from TFA) found that they can reverse the clinical entity known as Parkinson's disease by altering the function of that enzyme. That's first.

      Then they have to find something (a drug or other treatment modality) that alters enzyme function that can get into brain (not easy) and not trash everything else in sight and / or create more problems than it solves.In this case, the bar is going to be set fairly high.

      There are countless potential medical breakthroughs stuck at this stage. Very interesting, likely very important. Very speculative.

      • Re: (Score:3, Insightful)

        by afidel (530433)
        I'm more questioning the whole process of drug development and approval as it applies to diseases that are always fatal. I think the modern western approach has gone too far along the "it must be perfect for approval" path with the attached very high cost without showing that it has eliminated or even greatly reduced risk vs a more relaxed approval approach. Sure for a drug like Viagra perhaps the bar should be set high as the gain from the drug is fairly minimal in comparison to the potential problems but
        • Re: (Score:3, Insightful)

          by Qzukk (229616)

          if you are talking about eliminating Parkinsons or non-Hodgkin's lymphoma then the bar should probably be lower

          The problem with this approach is that the worse the disease, the more snake-oil you can find out there, promising to cure you and your wallet of all of your ills.

          • Re: (Score:3, Informative)

            The problem with this approach is that the worse the disease, the more snake-oil you can find out there, promising to cure you and your wallet of all of your ills.

            For something that IS time sensitive like Parkinson's, I'd not lower the bar on claims, I'd lower the bar on the risk aspect.

            In otherwords, lets say I make a claim that my drug does "A". I would like for the FDA to evaluate it for "A" and the major risks of "Will this likely hurt me more than help?"

            Then once "A" has been sufficiently proven, and

      • Re: (Score:3, Informative)

        by sjames (1099)

        You're at least comparing apples, oranges, and pears here.

        The current meds can help alleviate the symptoms of the disease, but do nothing to arrest it's progress. Eventually, the disease progresses until the drugs cannot help anymore.

        Various transplants aim to reverse the progression of the disease significantly. If it works, it's like starting over, but you still have a progressive degenerative disease and if you live long enough, you'll need another transplant.

        TFA is talking about a drug that would halt t

        • Re: (Score:3, Interesting)

          by Caged (24585)

          There are about 2-3 'stages' of Parkinson's medication, depending on just how much advanced the illness is at time of diagnosis. The first line of defence is the best and has good, manageable, results with relatively few side effects. The initial medication (typically L-Dopa tablets) regimen is effective for approximately the first 8-10 years, with the other stages of treatment decreasing rapidly in effectiveness plus worsening physical and mental side effects.

          Remember that treating Parkinson's is essentia

      • by sonnejw0 (1114901) on Monday November 09, 2009 @06:30PM (#30040026)
        Protein Kinase C is a key enzyme activated by many very different pathways involved in many different functions across the board. Blocking it will affect innumerable systems.

        Saying Protein Kinase C is the key to neutralizing Parkinson's Diseases is like saying Money is the key to the Financial Crisis. ... Duh.

        The clinical effects of Parkinson's Disease are the result of neuron death. You can't reverse the effects. Even if you induce neuronal growth, the brain will have to relearn the connections it needs to make, which took a lifetime to form. Forget about playing the piano again. You'll have to relearn to play (although you'll still have the conceptual knowledge).
        • by Andvari (685645)

          Even if you induce neuronal growth, the brain will have to relearn the connections it needs to make, which took a lifetime to form. Forget about playing the piano again. You'll have to relearn to play (although you'll still have the conceptual knowledge).

          Wrong. The striatum (which governs procedural memory) is only indirectly affected in parkinson's. Parkinson's is caused by the death of dopamine producing cells in the substantia nigra which is the region that communicates with the striatum. The memory of these movements (such as playing a piano) is still there, but the ability to access them is not. One of the things that is noticeable about parkinson's patients is that many of the jerky movements and tics caused by the medication are often movements t

    • Re: (Score:2, Insightful)

      by Caged (24585)

      Be aware that this cure won't reverse degeneration that has already occured.

      It will merely hault the progression of Parkinson's so that those in the future diganosed with this illness do not have to fear a slow, lingering decrease in their ability to function in society.

      Sadly, this news is 20 years too late to help my father.

      • This news is too late for a lot of people. However, preventing further damage is the first step in recovery (if recovery is possible). While the brain isn't technically viewed as a resiliant organ, it can partially recover if given enough time.

        If we can stop the damage causing element, I wouldn't be surprised (I wouldn't hold my breath) if the damage reversed itself over time (which could be decades)

        • by EvilPhil (1648481)
          Stopping the progression is a pretty big step. You do adapt to the disease if the progression is slow such as in the young onset forms. I suspect that many don't quite realize that not all adaptations are favorable. For instance, when your dopamine comes in pill form, or is moderated by something in pill form you can have a period of mania after you take the pills, and a suicidal depression that lasts for a few minutes before going to sleep. After years of this one tends to get a little scrambled up upsta
    • by vlm (69642)

      Since the disease leads to paralysis then death how safe does it have to be to be effective? If the cure kills 5% of the people that take it I would think that will be less than the 10 year delay in getting a "perfect" cure out of the lab and through FDA testing.

      Unfortunately, if you give that treatment to everyone, after 5% die, you'll have no one left to experiment on to find an even newer cure that kills no one. Or even worse, you'll find out that half the dosage of the same stuff, cures them just as well without killing anyone at all.

      Also the hypothesis is always that its a cure, because that is better for research grants. Of course, if you give it to everyone in an uncontrolled manner, if it doesn't work, which would not be entirely surprising, then ten year

      • Unfortunately, if you give that treatment to everyone, after 5% die, you'll have no one left to experiment on to find an even newer cure that kills no one. Or even worse, you'll find out that half the dosage of the same stuff, cures them just as well without killing anyone at all.

        Believe me they do multiple dosage in the trials. This is presuming the worst case scenario. Also I wish that PD would magically disappear and that there would be never be a new case.

      • Re: (Score:3, Insightful)

        by afidel (530433)
        You're making it a black and white issue, under your assumption it's either snake oil or it's a perfect cure. In the real world there are shades of grey and we are shooting for (and paying for) 99.9% black but are probably really getting 97% black when we get anything at all, many diseases go untreated because it's too expensive to develop a drug with a small potential patient set. What I'm proposing is relaxing things to a target of say 95% black when the disease warrants it. It's kind of like uptime in IT
        • by samkass (174571)

          I think things ARE relaxed and graded according to how the disease warrants it. For example, a children's Rotavirus vaccine was pulled off the market in 1999 because an extra ~5 out of 1,000,000 children had an adverse reaction (ie. the vaccine was 99.9995% safe) than was expected by statistical analysis. On the other hand, cancer treatments which cause a great deal of toxicity but which extend life an extra few months are regularly approved. You may feel the scale isn't set quite right, but I think qual

    • by giorgist (1208992)
      "Do no harm"

      It should improve the rest, or at least we shoudl be able to stop treatment for those that it doesn't.

      G
  • by dintlu (1171159) on Monday November 09, 2009 @03:12PM (#30037400)

    They say the first thing you hear about research or technology is the best thing you will ever hear about it.

    I'm not so sure "neutralizing" this kinase-C will result in any miracle cures, as the protein happens to have a lot of other uses in the body, per wikipedia:

    "Recurring themes are that PKC is involved in receptor desensitization, in modulating membrane structure events, in regulating transcription, in mediating immune responses, in regulating cell growth, and in learning and memory"

    • by smellsofbikes (890263) on Monday November 09, 2009 @03:34PM (#30037744) Journal
      There are a bunch of different types of protein kinase c (known as isozymes: they do the same general thing, reduce the energy it takes for compound A to turn into compound B, but they're different enzymes) so one possibility is targeting only the PKC that's in the brain, and another would be to target only this specific isozyme, but I can't find anything that says *which* isozyme this one is.

      Personally, I'm more curious about why PKC is doing this: if we could figure out how/why the dopamine-producing cells are getting killed by PKC and reduce their vulnerability, that seems like it would be a less systemic way of getting the same result than trying to reduce PKC's activity. It'd likely have fewer side-effects since it would only affect the cells getting attacked, rather than all the other cells that need PKC for their normal function.

      • by smellsofbikes (890263) on Monday November 09, 2009 @03:54PM (#30038034) Journal
        Sorry to reply to my own post but the PKC in question is protein kinase C delta [aspetjournals.org], which is involved in a buttload of important pathways [wikipedia.org], and shutting it off would be problematic even if you could just kill it without messing with any other of the PKC family. PKC's are used throughout the body, since they add a phosphate group onto other enzymes, which is a sort of tagging system to mark the modified enzymes or activate them and allow them to do other things, but the specific effects/results vary depending on the cell. Metabolic and transcriptional control systems are *truly* complicated. So, in *my* (definitely not professional) opinion, I'm going to reiterate: it's very useful to have evidence that PKC-delta is responsible for killing dopamine-producing cells, but finding out why they're being killed seems a lot more useful theraputically than trying to reduce PKC-delta's activity/concentration. Maybe it's as simple as a defective cell-surface receptor that's getting modified by PKC-delta and we can target that, specifically.
    • by Pedrito (94783) on Monday November 09, 2009 @03:43PM (#30037874) Homepage
      I'm not so sure "neutralizing" this kinase-C will result in any miracle cures, as the protein happens to have a lot of other uses in the body, per wikipedia:

      First of all, there isn't just one Protein Kinase C. There are a number of different versions with different jobs. Hence the list of the various isozymes in the article. The one in question is Protein Kinase C delta (PKC), and is NOT covered in the wikipedia article.

      PKC mediates apoptosis, or programmed cell death, in certain dopamine producing neurons. By blocking the enzyme, you can prevent the apoptosis. Reading some of Dr. Kanthasamy's papers, it's clear that he's already found some agents that do this in animal models. This is, of course, a long way from human trials (10 years if things go well, I believe is what he said in the article). But this is very promising avenue of research.

      What I can't figure out is why this is recent news. Dr. Kanthasamy has clearly been following this line of research for a few years. There's a 2007 paper entitled Neuroprotective Effect of Protein Kinase C{delta} Inhibitor Rottlerin in Cell Culture and Animal Models of Parkinson's Disease [sciencemag.org], so clearly he had already connected PKC with PD and was already investigating agents to block it.
      • by Pedrito (94783)
        Hmmm. For some reason, my delta character didn't show up. Should be 'PKCd' where the 'd' is a little delta. Oh well. :(
    • by OG (15008) on Monday November 09, 2009 @03:44PM (#30037890)

      There are many different forms of PKC, including PKC delta, the one that seems to be in question here according to recent publications from this lab. Specifically, a caspase enzyme is cleaving PKC delta into a smaller protein, and it's this cleaved version that appears to be causing the damage to the dopamine neurons in the nigra. Caspases mediate programmed cell death, and the compound in the paper I looked at blocks a certain caspase that was activated by the presence of certain metals.

      So while PKC and caspases are found widely throughout the body, there's actually a fair degree of specificity in the current model. Of course it's still early, and there are things to worry about, such as a possible increased likelihood for cancer (caspase 3 may be involved in breast cancer). But if this particular interaction between capase 3 and PKC delta can be successfully blocked without harm to other systems, we may have a good treatment on our hands.

      • by Eskarel (565631)

        I dunno about you, but I reckon most people would take an increased risk of breast cancer(or even a straight up mastectomy) over what happens to you with PD, not a fun way to die as I understand it and die you will.

    • by reverseengineer (580922) on Monday November 09, 2009 @04:01PM (#30038128)
      "Protein kinase C" is really at least 10 different proteins in humans- "isozymes" that have similar function, but different structures and different regulation mechanisms. All of the protein kinaseC variant belong to the larger class of serine/threonine kinases (about 100 different enzymes), and all the work that any of those enzymes do is to add a phosphate group to a serine or threonine amino acid on a protein. That role is important because protein phosphorylation is used as a molecular switch to activate or deactivate a protein. There's nothing special about this particular protein kinase-C isozyme, other than the target it phosphorylates.

      Presumably, the target of this particular kinase C form is involved in the apoptosis pathway for dopamine-releasing neurons, so keeping the molecular switch from being turned on could prevent the cell death from being carried out. Since the structures of isozymes are different, you could develop a drug that knocks out this variant of PKC without turning off PKC globally.

      However, preventing apoptosis of neurons, while possibly leading to an effective treatment, still does not address why brain cells would feel the need to kill themselves. For instance, in at least some Parkinson's patients, neurons suffer from a buildup of improperly folded protein called alpha-synuclein (compare amyloid and tau in Alzheimer's, prions in prion diseases). (However, overall there are many possible causes of Parkinson's and related syndromes, including unknown causes.) Cell suicide is meant as a protective measure for the remaining cells so they are not in turn poisoned by the output of misfolded proteins. What happens when you turn off apoptosis, and cells which turn "sick" are no longer able to die?
  • Is the dopamine-hindrance the primary cause of Parkinson's? Is Parkinson's generally associated with depression due to lack of dopamine?
    • Re: (Score:3, Informative)

      Same substance, different parts of the brain. There are several different pathways that involve the release of dopamine; the mesolimbic pathway is where most of the behavioral functions of dopamine occur, and the nigrostriatal pathway, which is involved in motor control. In Parkinson's, the dopamine releasing neurons of the substantia nigra (at one end of the nigrostriatal pathway) die, leading to the characteristic motor symptoms. However, many drugs that act on dopamine pathways, particularly older one
  • ... Certain typical Anti-Psychotic medicine, like Haldol [wikipedia.org], which typically exhibit the side-effect of Parkinson-like-symptoms ?
  • Really, I'm curious to know?

    I mean, if you find something really promising, don't you try to accelerate the testing?

  • Cure, eh? (Score:3, Insightful)

    by TheModelEskimo (968202) on Monday November 09, 2009 @03:49PM (#30037946)
    Have we seen any real cures via treatments lately? I honestly don't know, but there sure are a lot of maintenance-level medications out there. Is there a treatment or a pill out there that can just cure you flat out, when your body wouldn't do so on its own?
    • Re: (Score:2, Insightful)

      by Anonymous Coward

      I would think that a drug that prevents a bad thing from happening is a cure. Yes, there are side effects, and yes, there are costs, but extending and enhancing quality of life is a pretty good definition of a cure to me.

      There might, and probably will be, drugs that eliminate cancers. Once such things occur, it might/will be possible to reduce or eliminate dosage. Many other diseases are a lack-of or an excess-of in the body. Short of genetic modification, what you can do in these cases OTHER than to pr

    • Re:Cure, eh? (Score:4, Insightful)

      by mea37 (1201159) on Monday November 09, 2009 @04:54PM (#30038902)

      I don't know your intentions, but you seem to be insenuating a shift in the approach medicne is taking. I'd say there's not really a change.

      Big breakthroughs in early medicne were things like antibiotics. Because the diseases they treat are caused by bacteria, and because you can eliminate all of the bacteria causing a given illness, cure is a reasonable goal.

      Viral or fungal infections, or cancers, are similarly things where it makes sense to hope for a cure. Any condition that's caused by somethign attacking your otherwise-functional body might potentially be cured.

      But as our lives get longer, and the number of deaths attributed to bacteria, etc. decrease, more and more of the conditions that have our attention are caused by some abnormal function of the body itself. The body is a complex and dynamic place; it's a bit much to hope that acute administration of a chemical will forever alter whatever defect is causing a problem. Suppose, for example, that the cause is ultimately genetic; then every cell is propagating the root cause. If you can interfere with the operation of the disease so as to eliminate - or sometimes even just reduce - symptoms, that's a great result; but it probably does mean you'll be on a maintenance medicine.

      Modern medicine is still looking for cures, but the problems we're facing are a lot harder now that the lowest-hanging fruit has been taken.

    • When I was a kid 20-mumble years ago, I knew someone who got Hodgkin's lymphoma (or "disease" at the time). His family prepared for the inevitable death that was to come a few months later. Today, the cure rate is 90% - it's the cancer you want to get if you're going to have one. I'm personally pretty happy with the cure rates we're seeing in some previously fatal diseases.

  • by Anonymous Coward

    This research is a bottom-up approach, working to understand the details of the disease and then develop a cure at the most fundamental level possible. This is why this group doesn't have a treatment out there yet- he's not trying to treat the symptoms, he seems to be doing a very thorough job of dissecting the problem (at least based on the abstract from his latest paper).
    Here's the abstract (abstracts are public domain):
    Toxicol Appl Pharmacol. 2009 Oct 15;240(2):273-85. Epub 2009 Jul 29.
    Vanadium induces d

  • pardon me? (Score:1, Insightful)

    by Anonymous Coward

    "10 years" and "major breakthrough"? Somethind doesn't add up here.

    • Ten years is fast in terms of human subjects - it takes a while to get informed consent, and a period of 7 to 10 years is common for such drug trials to reach the final stages.

      We've had a cure for half of all cancers for years now, but the trials and consents make it difficult to complete it quickly (especially as you have humans with cancer at the later stages, after you complete the mouse and primate models).

  • People have been working on finding selective inhibitors of the various PKC isozymes for about 20 years. There are, supposedly, a number of diseases that will be cured when the right ones are found. This target has the added difficulty of being behind the blood-brain barrier. Although it is possible that a selective inhibitor of PKC delta that makes it through the blood-brain barrier and does what it is supposed to do and not a lot of other things, will be found in the next ten years; ten years is an en
  • While this will help - a lot - if after 7-10 years a cure completes human trials - it won't fix the mitochondrial damage that has already taken place.

    However, a period of fasting (10-14 days) should force telomere resets in most cells and force a mitochondrial rebuild, which might work as a follow up to this.

    • by Slashcrap (869349)

      However, a period of fasting (10-14 days) should force telomere resets in most cells and force a mitochondrial rebuild, which might work as a follow up to this.

      The human body is not an MMO and tends not to work like one. Hope this helps, freak.

      • unlike you I actually work in research - specifically involving Alzheimer's, Parkinson's, Autism, and Lipids.

        I stand by my statement on mechanisms.

  • Title should read "dopamine producing cell killers"

    The research may lead to a treatment to stop the progression. It cannot lead to a 'cure'. By the time symptoms are noticed, about 2/3 of the dopamine producing cells are dead. No matter how loud and clear you tell the remaining cells to stop dying off ('halting apoptosis'; essentialy what the research is about), the dead ones stay dead.

    There is already a (partial) cure for Parky's: fetal stem cell injection. It worked 20 years ago, and it'd work today if it

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