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Researchers Neutralize Parkinson's Dopamine Killers

ScuttleMonkey posted more than 4 years ago | from the knowing-is-half-the-battle dept.

Medicine 105

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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I don't know (4, Funny)

killmenow (184444) | more than 4 years ago | (#30037300)

This research seems kinda shaky.

Re:I don't know (0, Insightful)

Anonymous Coward | more than 4 years ago | (#30037348)

I'm all for making fun of people who get injured by their own stupidity. I'm talking about the guys who decide to skateboard off of the roof of a 3 storey house, and end up breaking their penises or permanently damaging their scrotums.

But please, show some respect for those who are cursed with a disease or disability that they had no control over.

Re:I don't know (2, Funny)

Anonymous Coward | more than 4 years ago | (#30037382)

But please, show some respect for those who are cursed with a disease or disability that they had no control over.

Like stupidity?

Re:I don't know (0)

Anonymous Coward | more than 4 years ago | (#30038652)

Please, have some respect. The polite term for those people is "Republicans".

Re:I don't know (0)

Anonymous Coward | more than 4 years ago | (#30039860)

Objectivists.

Re:I don't know (3, Funny)

Parlett316 (112473) | more than 4 years ago | (#30037386)

What about Ali? Maybe he should have bobbed and weaved instead of rope a dope.

Re:I don't know (-1, Troll)

Anonymous Coward | more than 4 years ago | (#30037556)

Speaking of...

What do you call a leper in a pot of boiling oil?

Bob

Re:I don't know (1, Insightful)

swanzilla (1458281) | more than 4 years ago | (#30037658)

I'm all for making fun of people who get injured by their own stupidity. I'm talking about the guys who decide to skateboard off of the roof of a 3 storey house, and end up breaking their penises or permanently damaging their scrotums.

But please, show some respect for those who are cursed with a disease or disability that they had no control over.

I find your code of ethics fascinating.

Re:I don't know (2, Insightful)

noundi (1044080) | more than 4 years ago | (#30038666)

I'm all for making fun of people who get injured by their own stupidity. I'm talking about the guys who decide to skateboard off of the roof of a 3 storey house, and end up breaking their penises or permanently damaging their scrotums.

But please, show some respect for those who are cursed with a disease or disability that they had no control over.

I find your code of ethics fascinating.

I find ethics fascinating.

Re:I don't know (1)

sbeckstead (555647) | more than 4 years ago | (#30039402)

bucking for the Spock of the week award?

Re:I don't know (0)

Anonymous Coward | more than 4 years ago | (#30040112)

...And I'd like to subscribe to your newsletter.

Re:I don't know (0)

Anonymous Coward | more than 4 years ago | (#30039000)

My grandfather had Parkinson's and he would have laughed his ass off over that comment (incidentally he owned the T-shirt Hell t-shirt that said "I'm not getting jiggy, I have Parkinson's). It's like the kids my ex taught who had high-functioning autism. Several made the joke that they "rock!".

I've found that many people offended by the jokes like that don't actually belong to the group that the joke is about. It's all in good fun.

Re:I don't know (1)

tool462 (677306) | more than 4 years ago | (#30037806)

The insensitivity of this joke made me shudder.

Re:I don't know (0)

noundi (1044080) | more than 4 years ago | (#30038712)

This research seems kinda shaky.

That's not funny.

Re:I don't know (1)

makuabob (1035076) | more than 4 years ago | (#30038876)

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!

Re:I don't know (0)

Anonymous Coward | more than 4 years ago | (#30042752)

Ba-dum TSK.

huh? (0)

Anonymous Coward | more than 4 years ago | (#30037334)

'Once we find the compound, we need to make sure it’s safe. ... says Kanthasamy."

This is not quite doing it for me.

Re:huh? (5, Insightful)

icebike (68054) | more than 4 years ago | (#30037516)

It might do it for you if you had the disease.

If the side effects are more tolerable than the disease itself most people would opt to use the medicine. Waiting for perfect solutions has never really worked, especially for diseases that slowly rob you of any ability to manage your daily life.

Re:huh? (3, Interesting)

Chris Burke (6130) | more than 4 years ago | (#30038598)

It might do it for you if you had the disease.

If the side effects are more tolerable than the disease itself most people would opt to use the medicine. Waiting for perfect solutions has never really worked, especially for diseases that slowly rob you of any ability to manage your daily life.

Indeed. If and when it comes time to do trials in humans, they can probably expect to have volunteers lined up around the block. There are certain diseases where "we don't know if this is safe" is not that big a concern.

My godfather was in a study for an experimental treatment for a particular kind of leukemia. He was very close to entering the "acute" (as in acutely fucked) stage and the best matching marrow donor he'd found in years of searching would have left him with an under 10% chance of surviving the transplant if it came to that. He was sick and miserable thanks to his chemotherapy. So, what exactly did he have to lose? Not a whole hell of a lot. What was the outcome? The drug, as far as they could tell, cured him and everyone else in the study. All signs of leukemia vanished.

That's a long shot to happen in any particular case, but how many people who are facing nasty death if they don't try wouldn't be willing to take it?

On a related note, my graduate algorithms professor had a side gig of consulting for the medical industry. He related that he had worked on an algorithm for situations like this one, where as the study progresses and (assuming) the drug is showing signs of being effective you want to move people from the control group to the active group as quickly as possible while still maintaining the validity of the study. The algorithm was exponential in the size of the study, so study sizes or the ability to move people into the active group could be seriously constrained by available computing power. His optimizations (didn't change the big-O iirc) improved the performance and thus allowed larger study sizes and thus, as a result, could have literally saved lives.

Re:huh? (1)

praksys (246544) | more than 4 years ago | (#30038806)

Also worth keeping in mind that because this disease kills about 15,000 people a year in the US (and many tens of thousands world wide) every year of delay caused by over-regulation will kill many thousands of people.

Re:huh? (1)

hesaigo999ca (786966) | more than 4 years ago | (#30044786)

Not to call you on your bluff, but would you happen to have facts to these stories, as to which medication and which trial your grandfather was in, I could use it for MY grandfather, and would love to hear where this trail took place, I might book him a ticket right now

Re:huh? (1)

Chris Burke (6130) | more than 4 years ago | (#30047394)

The study took place over 5 years ago, so I don't remember much of the details. I could find out the non-marketing name of the drug, but I should warn you that it was only for his particular type of leukemia, which is one of the least common ones (I think roughly 3000 people have it in the U.S.).

Oh and not that it matters, but it was my godfather, as in my dad's best friend and the guy that would have become my legal guardian in the event that I was orphaned.

Re:huh? (1)

hesaigo999ca (786966) | more than 4 years ago | (#30048968)

Still would be nice to have some links if you could...thanks in advance..

Re:huh? (0)

Anonymous Coward | more than 4 years ago | (#30040066)

I'm the original AC.

Awarding Obama the Nobel prize is also not quite doing it for me.

Re:huh? (1)

jenik (1030872) | more than 4 years ago | (#30043140)

Protein kinase C is one of the most important intracellular signalling enzymes. If you block it in the whole organism you die pretty quickly. I.e. the trick is in blocking it selectively only in dopaminergic neurons. Let's say it's not trivial.

Wouldn't it be nice if this were NOT vapor? (1)

mr_stinky_britches (926212) | more than 4 years ago | (#30037360)

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.

speaking of vapor and dopamine release (0, Offtopic)

Anonymous Coward | more than 4 years ago | (#30037410)

http://www.storz-bickel.com/vaporizer/volcano-vaporization-system.html

the only true therapy with any real benefit.

Re:Wouldn't it be nice if this were NOT vapor? (3, Interesting)

icebike (68054) | more than 4 years ago | (#30037734)

Yes, it certainly would be nice.

Especially when you consider there appear to be links between Parkinson’s, Alzheimer’s.

http://pn.psychiatryonline.org/cgi/content/full/36/20/23-a [psychiatryonline.org]

There has been other research suggesting that understanding one of these diseases leads to avenues of research for the other.

Re:Wouldn't it be nice if this were NOT vapor? (1)

dj_tla (1048764) | more than 4 years ago | (#30038388)

I haven't done enough research on Alzheimer's to support the link between the two, but the destruction of dopamine-producing cells in Parkinson's surely has an effect on long-term memory.

http://www.sciencemag.org/cgi/content/abstract/325/5943/1017 [sciencemag.org]

A lack of dopamine affects other cognitive functions, so I can imagine seeing similar behavioural effects as one sees in Alzheimer's, but I'm not aware of Alzheimer's characteristic loss of neurons and synapses in Parkinson's disease. So the link between them seems a bit shady to me.

Re:Wouldn't it be nice if this were NOT vapor? (1)

simplexion (1142447) | more than 4 years ago | (#30041062)

Although Alzheimer’s disease (AD) and Parkinson’s disease (PD) are distinct neurological disorders, previous studies have indicated that as many as 25 percent of patients with AD develop PD-like symptoms, and some PD patients develop signs of AD as well.

It's pretty normal to lose your mind as you get old.

Re:Wouldn't it be nice if this were NOT vapor? (1)

hesaigo999ca (786966) | more than 4 years ago | (#30044798)

Really, you want that little bugger to still be around, I thought he died along time ago, when that show of his with heather locklear got cancelled.

Re:Wouldn't it be nice if this were NOT vapor? (1)

mr_stinky_britches (926212) | more than 4 years ago | (#30045766)

Back to the Future, dude. ;)

Hmm, how safe is safe enough? (4, Interesting)

afidel (530433) | more than 4 years ago | (#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:Hmm, how safe is safe enough? (2, Insightful)

jrmcc (703725) | more than 4 years ago | (#30037502)

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!!

Re:Hmm, how safe is safe enough? (0)

Anonymous Coward | more than 4 years ago | (#30037546)

As someone whose grandfather had Parkinson's disease, I can assure you that they are never short of volunteers for clinical trials. Those come before FDA approval.

Re:Hmm, how safe is safe enough? (3, Insightful)

ColdWetDog (752185) | more than 4 years ago | (#30037552)

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:Hmm, how safe is safe enough? (2, Insightful)

afidel (530433) | more than 4 years ago | (#30037794)

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 if you are talking about eliminating Parkinsons or non-Hodgkin's lymphoma then the bar should probably be lower as the potential gains are that it likely helps everyone it doesn't kill (who would have died shortly of the disease anyways).

Basically the reason so many cures are stuck at that early stage is that drug companies don't see a potential for profit because the system has become so cumbersome. I'm not normally a free-marketeer but perhaps the balance should be tipped back to the drug companies a bit for some classes of drugs?

Re:Hmm, how safe is safe enough? (2, Insightful)

Qzukk (229616) | more than 4 years ago | (#30038372)

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:Hmm, how safe is safe enough? (2, Informative)

IndustrialComplex (975015) | more than 4 years ago | (#30039088)

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 patients aren't immediately dying from liver failure or brain hemorrhages, I'd like to see the drug released with a medical disclaimer that it is still in the 'trial' phase and the negative effects have not yet been fully evaluated.

That way, you don't have snake oil (ineffective) treatments being sold, but you aren't holding off a treatment from someone who WILL die because the treatment may cause their hair to fall out. (Isn't that how we treat chemotherapy?)

Re:Hmm, how safe is safe enough? (2, Informative)

sjames (1099) | more than 4 years ago | (#30037900)

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 the progress of the disease right where it is. Whatever your level of function is, that's where it will stay using only this theoretical new drug. Presumably, you would then use other methods to either reverse the progress (knowing it won't progress again) or to alleviate the symptoms.

Yes, it's quite speculative, but IF it pans out, it could be a major improvement in the lives of Parkinson's sufferers.

Re:Hmm, how safe is safe enough? (3, Interesting)

Caged (24585) | more than 4 years ago | (#30038230)

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 essentially tampering with brain chemistry.

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.

Re:Hmm, how safe is safe enough? (0)

Anonymous Coward | more than 4 years ago | (#30039156)

If I'm understanding the article, this promises to provide a way to prevent the brain damage that causes Parkinson's in the first place. The current treatment is essentially treating the decreased dopamine in the brain; this sounds like a treatment for the *cause* of the decreased dopamine.

Current treatment isn't that great, since essentially you build up a tolerance for the drugs, it's a balancing act between providing patient function and getting the minimum dose, because the minimum dose will increase in time. Also the fact that too much of the will cause schizophrenia-like symptoms. Great fun.

If I had Parkinson's, I'd be willing to accept a risky treatment. Current treatment isn't that great.

Re:Hmm, how safe is safe enough? (0)

Anonymous Coward | more than 4 years ago | (#30041910)

If I had Parkinson's, I'd be willing to accept a risky treatment. Current treatment isn't that great.

My father has it and I can tell you he's reached the point where he'd take any risk. The schizophrenia-like symptoms are very hard on the family and cause huge problems at an facility he lives in.

Re:Hmm, how safe is safe enough? (5, Informative)

sonnejw0 (1114901) | more than 4 years ago | (#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).

Re:Hmm, how safe is safe enough? (0)

Anonymous Coward | more than 4 years ago | (#30041762)

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).

Right on.

Also, I think it's important to note that the name of the enzyme they are studying is indicative of how far detached it is from actual dopamine inhibition or destruction. Dopamine is not a protein, therefore the most immediate way that PKC can affect it is by activating an enzyme that can.

It seems to me that (if the summary is accurate) this isn't very useful information. Of course it's easier said than done, but the important information is in HOW PKC is affecting dopamine levels, not the mere fact that it is.

Re:Hmm, how safe is safe enough? (0)

Anonymous Coward | more than 4 years ago | (#30042022)

It's not necessarily that bad. The substantia nigra is part of a feedback error correction system (the extended basal ganglia), so it may well be possible to regrow functional connections as an adult. And while yes, any general PKC blocker is going to be fairly dirty, it might be possible to find an antagonist specific to the subtype involved in this pathway (whatever it is, I didn't see enough detail there ... I'm assuming some sort of signal transduction pathway specific to dopamine receptors).

Even if you can't, from what I understand, part of the etiology of PD is free radical damage (dopamine is a fairly reactive chemical) so reducing PKC activity just a little bit may be enough to stop the progression of the disease without adversely affecting everything else.

Re:Hmm, how safe is safe enough? (1)

Andvari (685645) | more than 4 years ago | (#30042614)

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 that would otherwise be normal in a different setting (some of the ones I've seen include: moving pieces on a chess board, dancing and writing on a blackboard).

Re:Hmm, how safe is safe enough? (1)

sonnejw0 (1114901) | more than 4 years ago | (#30047486)

I stand corrected.

Re:Hmm, how safe is safe enough? (0)

Anonymous Coward | more than 4 years ago | (#30040478)

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.
 

Create more problems than it solves? If it doesn't work they die anyway... what's the risk?

Re:Hmm, how safe is safe enough? (2, Insightful)

Caged (24585) | more than 4 years ago | (#30038106)

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.

Re:Hmm, how safe is safe enough? (1)

IndustrialComplex (975015) | more than 4 years ago | (#30039158)

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)

Re:Hmm, how safe is safe enough? (1)

EvilPhil (1648481) | more than 4 years ago | (#30041914)

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 upstairs. Psychosis is one of those little "whoopsie" features of jumpstarting dopamine conversion with tyrosine or carbodopa, and all the rest. It hit about 30% who take relatively high amounts. As for the percentage of people who are convinced that people are out to get them, or some other effect comprable to hitting that caffeine too hard, who can say. And then there are the extreme ends, the ones who want to kill the fundies so they can get their stem cells and go back to being functional again, or who are looking down on hitting stage three and possibly looking at just a little bit of payback. Worst case maybe you get the chair before you hit stage four, or wait, maybe that would be the upside. ;)

Re:Hmm, how safe is safe enough? (1)

vlm (69642) | more than 4 years ago | (#30038216)

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 years later when 100% die, you have to start all over again, except you've wasted ten years.

And then too, bad money always pushes out good money if the purchasers are ignorant, and all customers of medical treatment are ignorant, so no free medical market can exist, so.... A scammer could make a lot of dough, for awhile, by pushing something that doesn't work but is marketed well, look at the supplement and diet industries for example. So you need a system that prevents intentional failures from being marketed, otherwise we'd end up with only scams, because dreaming up scams is cheaper than real research. So to save everyone else from some totally different scam, we have to prove this real treatment isn't a scam, even if it takes awhile. And its only fair, since if we didn't prevent other scams in the past, this guy would never have gotten research money to find a real treatment, since it would have been more profitable to invest in a scam.

Thus the policy of careful testing, in the long run, is more humane, even if in the short run it looks bad.

Re:Hmm, how safe is safe enough? (1)

AlexBirch (1137019) | more than 4 years ago | (#30038528)

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:Hmm, how safe is safe enough? (2, Insightful)

afidel (530433) | more than 4 years ago | (#30038550)

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, most organizations don't need 5 9's uptime and can't afford it so they go for something more affordable which still brings significant benefits to the organization.

Re:Hmm, how safe is safe enough? (1)

samkass (174571) | more than 4 years ago | (#30038794)

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 qualitatively things are the way you suggest they should be.

don't think -- *know* (0)

Anonymous Coward | more than 4 years ago | (#30039524)

http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/SpeedingAccesstoImportantNewTherapies/ucm128291.htm [fda.gov]

FDA's explanation of Accelerated Approval, Priority Review and Fast Track for getting drugs to the market faster. It's a little sad that (in the FDA's own words) "drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists" are still talking an average of 50% as much time to get FDA approval as "a drug that offers at most, only minor improvement over existing marketed therapies". You can thank the drug company lobbying that pushed the FDA (via 2002's amendments to PDUFA) to focus more of their resources on those minor-improvement drugs so that PHRMA can keep extending the patents on their money makers.

Re:Hmm, how safe is safe enough? (1)

giorgist (1208992) | more than 4 years ago | (#30039912)

"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

Skepticism may be warranted, here. (2, Interesting)

dintlu (1171159) | more than 4 years ago | (#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"

Re:Skepticism may be warranted, here. (4, Insightful)

smellsofbikes (890263) | more than 4 years ago | (#30037744)

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.

Re:Skepticism may be warranted, here. (4, Informative)

smellsofbikes (890263) | more than 4 years ago | (#30038034)

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.

Re:Skepticism may be warranted, here. (4, Informative)

Pedrito (94783) | more than 4 years ago | (#30037874)

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.

Re:Skepticism may be warranted, here. (1)

Pedrito (94783) | more than 4 years ago | (#30037912)

Hmmm. For some reason, my delta character didn't show up. Should be 'PKCd' where the 'd' is a little delta. Oh well. :(

Re:Skepticism may be warranted, here. (3, Informative)

OG (15008) | more than 4 years ago | (#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.

Re:Skepticism may be warranted, here. (1)

Eskarel (565631) | more than 4 years ago | (#30043052)

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.

Re:Skepticism may be warranted, here. (3, Informative)

reverseengineer (580922) | more than 4 years ago | (#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?

Re:Skepticism may be warranted, here. (1)

unifyingtheory (1357069) | more than 4 years ago | (#30042168)

What happens when you turn off apoptosis, and cells which turn "sick" are no longer able to die?

Cancer.

Re:Skepticism may be warranted, here. (1)

simoncpu was here (1601629) | more than 4 years ago | (#30043044)

What happens when you turn off apoptosis, and cells which turn "sick" are no longer able to die?

Zombies!

Parkinson's Disease questions (1)

oldhack (1037484) | more than 4 years ago | (#30037402)

Is the dopamine-hindrance the primary cause of Parkinson's? Is Parkinson's generally associated with depression due to lack of dopamine?

Re:Parkinson's Disease questions (0)

Anonymous Coward | more than 4 years ago | (#30038090)

My wife's grandmother takes large doses of dopamine-boosting drugs, which is interesting in that my wife takes large doses of dopamine-reducing drugs to help with her mania.

A manic-depressive with Parkinson's is almost beyond help.

Re:Parkinson's Disease questions (2, Informative)

reverseengineer (580922) | more than 4 years ago | (#30038422)

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 ones, tend to be nonspecific, and can produce side effects from working on the other pathways- like the movement disorders associated with antipsychotic drugs, for instance.

Re:Parkinson's Disease questions (1)

oldhack (1037484) | more than 4 years ago | (#30039566)

Thanks for that.

What about my buzz? (-1, Troll)

RiotingPacifist (1228016) | more than 4 years ago | (#30037572)

Will these new drugs, help me keep my buzz going for longer? If so will somebody please think of the children!

So how does this relate to.... (2, Interesting)

lbalbalba (526209) | more than 4 years ago | (#30037594)

... Certain typical Anti-Psychotic medicine, like Haldol [wikipedia.org] , which typically exhibit the side-effect of Parkinson-like-symptoms ?

Re:So how does this relate to.... (0)

Anonymous Coward | more than 4 years ago | (#30038184)

Anti-psychotic drugs act to reduce dopamine levels in the brain. Parkinson's has as a cause or symptom low dopamine levels in the brain. There's a clear correlation. The fact that people taking the drug show other signs of Parkinson's enhances that correlation, and leads me to hypothesize that the reduced dopamine is a cause of the other Parkinson's symptoms, not just a correlated effect.

Re:So how does this relate to.... (1)

lbalbalba (526209) | more than 4 years ago | (#30038648)

leads me to hypothesize that the reduced dopamine is a cause of the other Parkinson's symptoms, not just a correlated effect.

yeah, I was kinda hoping for that... :)

How do they calculate the time needed (1)

WormholeFiend (674934) | more than 4 years ago | (#30037604)

Really, I'm curious to know?

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

Re:How do they calculate the time needed (0)

Anonymous Coward | more than 4 years ago | (#30037670)

It comes down to funding and bureaucracy. With experience you can gauge how long things will take...it's often not the science that holds these things up.

Re:How do they calculate the time needed (2, Insightful)

PotatoFarmer (1250696) | more than 4 years ago | (#30037996)

Probably has something to do with the length of time necessary to complete Clinical Trials [wikipedia.org] for FDA (or equivalent regulatory agency) approval. Given that this process is still in the research phase and has not yet progressed to a testable drug state, 10 years sounds about right.

Re:How do they calculate the time needed (2, Informative)

jbeaupre (752124) | more than 4 years ago | (#30038262)

This might explain why: http://www.usatoday.com/money/industries/health/drugs/2006-08-23-drug-lawsuits-usat_x.htm [usatoday.com]

Willing to risk the entire company by taking a few shortcuts? Ethically you might say it's worth it. Better for a company to risk death than a person. But that's not how things are decided. Both have to live. And that takes a lot of time.

BTTF 4 (0)

Anonymous Coward | more than 4 years ago | (#30037704)

Finally, M.J.Fox can make Back To The Future 4 !

Excellent! (-1, Troll)

Anonymous Coward | more than 4 years ago | (#30037816)

That sounds really dope!

Research Completely Wrong (0, Flamebait)

frankxcid (884419) | more than 4 years ago | (#30037884)

These scientists are completely off their rockers. Don't they know that it is embryonic stem cells and the defeat of Bush that is the real cure for Parkinsons. Thank you Michael J Fox!

Cure, eh? (2, Insightful)

TheModelEskimo (968202) | more than 4 years ago | (#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:Cure, eh? (2, Insightful)

Anonymous Coward | more than 4 years ago | (#30038358)

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 provide "maintenance-level medications". Hell, most people won't consider a GM tomato. How the @(&%!#@ will they do it to themselves??

Re:Cure, eh? (3, Insightful)

mea37 (1201159) | more than 4 years ago | (#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.

Re:Cure, eh? (1)

Just Some Guy (3352) | more than 4 years ago | (#30039736)

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.

Re:Cure, eh? (0)

Anonymous Coward | more than 4 years ago | (#30040722)

Treatments that can cure you when your body can't do it on it's own? Ever heard of tuberculosis? Or any serious infectious disease?

Here's the abstract: (1, Insightful)

Anonymous Coward | more than 4 years ago | (#30038512)

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 dopaminergic neurotoxicity via protein kinase Cdelta dependent oxidative signaling mechanisms: relevance to etiopathogenesis of Parkinson's disease.
Afeseh Ngwa H, Kanthasamy A, Anantharam V, Song C, Witte T, Houk R, Kanthasamy AG.

Environmental exposure to neurotoxic metals through various sources including exposure to welding fumes has been linked to an increased incidence of Parkinson's disease (PD). Welding fumes contain many different metals including vanadium typically present as particulates containing vanadium pentoxide (V2O5). However, possible neurotoxic effects of this metal oxide on dopaminergic neuronal cells are not well studied. In the present study, we characterized vanadium-induced oxidative stress-dependent cellular events in cell culture models of PD. V2O5 was neurotoxic to dopaminergic neuronal cells including primary nigral dopaminergic neurons and the EC50 was determined to be 37 microM in N27 dopaminergic neuronal cell model. The neurotoxic effect was accompanied by a time-dependent uptake of vanadium and upregulation of metal transporter proteins Tf and DMT1 in N27 cells. Additionally, vanadium resulted in a threefold increase in reactive oxygen species generation, followed by release of mitochondrial cytochrome c into cytoplasm and subsequent activation of caspase-9 (>fourfold) and caspase-3 (>ninefold). Interestingly, vanadium exposure induced proteolytic cleavage of native protein kinase Cdelta (PKCdelta, 72-74 kDa) to yield a 41 kDa catalytically active fragment resulting in a persistent increase in PKCdelta kinase activity. Co-treatment with pan-caspase inhibitor Z-VAD-FMK significantly blocked vanadium-induced PKCdelta proteolytic activation, indicating that caspases mediate PKCdelta cleavage. Also, co-treatment with Z-VAD-FMK almost completely inhibited V2O5-induced DNA fragmentation. Furthermore, PKCdelta knockdown using siRNA protected N27 cells from V2O5-induced apoptotic cell death. Collectively, these results demonstrate that vanadium can exert neurotoxic effects in dopaminergic neuronal cells via caspase-3-dependent PKCdelta cleavage, suggesting that metal exposure may promote nigral dopaminergic degeneration.

pardon me? (1, Insightful)

Anonymous Coward | more than 4 years ago | (#30038700)

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

Re:pardon me? in research speed is slow (1)

WillAffleckUW (858324) | more than 4 years ago | (#30039422)

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).

Old target (1)

methano (519830) | more than 4 years ago | (#30039210)

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 entirely speculative number. What it means is somewhere between 5 and forever. Also, given that there will be no organic chemists left in the US to do the work of this discovery, expect it to be an imported product.

Please note this won't reverse mitochondrial dmg (1)

WillAffleckUW (858324) | more than 4 years ago | (#30039404)

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.

Re:Please note this won't reverse mitochondrial dm (1)

Slashcrap (869349) | more than 4 years ago | (#30043618)

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.

Press release long on hype, short on substance! (0)

Anonymous Coward | more than 4 years ago | (#30039474)

I can't fathom what this article is doing here.

First, it links to a blog, that reprints the text of Iowa State University's over-hyped press release. If Slashdot it going to print hype, why not link directly to the source?

Second, the supposedly new compound discovered by Dr. Kathasamy that neutralizes PKC-delta is never named in the press release at all.

Third, no published research is cited in the press release.

Fourth, a Pubmed.gov search for Dr. Kathasamy's work finds articles on the dopamine killing protein PKC-delta dating back to the year 2003, and referencing research done on the neurotoxic effects of this protein dating back to the early 1990's.

Fifth, Dr. Kathasamy's articles published in 2003 and 2007 described results in cell cultures, and in animals, not in humans. Although he reported interesting results in those early studies, any clinical application of that work is merely conjecture at this point, and certainly years off in the future, if it ever materializes at all.

Sixth, those same articles include references to other promising results to block the neurotoxic effect of PKC-delta and its role in Parkinson's disease, which were obtained by other researchers in 1999, using a natural supplement, creatine, which was already being studied in clinical trials in human subjects. The studies with creatine, and also Co-Q10, which have been repeated by many researchers around the world have shown consistently good results, and also long-term safety. So why don't they tell us exactly what it is that is so special about Dr. Kathasamy's work to justify such hype?

All of which makes me want to know why Iowa State University issued the press release last week in the first place? Where is the alleged breakthrough? Why are they hyping something that is so far away from any possible clinical application? Why did they provide no details about the purported "key to possibly cure Parkinson's disease? What is this all really about?

2400 mg Co Q10 (0)

Anonymous Coward | more than 4 years ago | (#30040414)

2400 mg of Co Q10 with 1200 IU of vitmamin E - works well. I know someone who has Parkinsons - and the CO Q10 basically stopped the progression of the disease for the last 4 years.

Less than 1200 mg of CO Q10 has very little effect. Co Q10 without Vitamin E also has little effect. They did a study with 300 mg and found no difference with the Placebo. A study with 1200 mg found 44% difference with Placebo. I think 2400 mg is regarded as the optimum level.

The problem is that Co Q10 is sometimes either expensive or bad quality. And patients try to save by either taking cheap Co Q10 or less of it.

Here are some studies pro and against:

For (2002 NIH study at 800 mg and 1200 mg):
http://www.ninds.nih.gov/news_and_events/news_articles/pressrelease_parkinsons_coenzymeq10_101402.htm

Against (2007 German study but 300 mg):
http://www.sciencedaily.com/releases/2007/05/070514174229.htm

Current Clinical Trial (started 2008 with 1200 mg and 2400 mg):
http://clinicaltrials.gov/ct2/show/NCT00740714

Re:2400 mg Co Q10 (0)

Anonymous Coward | more than 4 years ago | (#30040490)

Of course, this is based on someone I know. Each person could be different. And there could be other factors why the disease stopped.

But it seemed to me to have a pretty direct correlation to Co Q10. And I know of someone else who was on high doses of meds and shaking. He started Co Q10 and cut his meds in half. He seems about the same, but his nightmares from the meds are a lot less.

Exercise is also a huge help in slowing the progression.

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Not A Cure (1)

DynaSoar (714234) | more than 4 years ago | (#30042574)

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 were allowed. The above research isn't required for this, but it would prevent loss of other original neurons.

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