Slashdot Mirror
Researchers Neutralize Parkinson's Dopamine Killers
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."
This research seems kinda shaky.
Wouldn't it be nice if this were NOT vapor? I'd like to see Michael J. Fox be able to stay around as long as possible.
Here's to hoping this pans out. Cheers.
Censorship is obscene. Patriotism is bigotry. Faith is a vice. Slashdot 2.0 sucks.
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.
There are 4 boxes to use in the defense of liberty: soap, ballot, jury, ammo. Use in that order. Starting now.
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"
Is the dopamine-hindrance the primary cause of Parkinson's? Is Parkinson's generally associated with depression due to lack of dopamine?
Fuck systemd. Fuck Redhat. Fuck Soylent, too. Wait, scratch the last one.
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.
Sig Battery depleted. Reverting to safe mode.
... Certain typical Anti-Psychotic medicine, like Haldol, 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?
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?
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.
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.
The enemies of Democracy are
"10 years" and "major breakthrough"? Somethind doesn't add up here.
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.
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.
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.
-- Tigger warning: This post may contain tiggers! --
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).
-- Tigger warning: This post may contain tiggers! --
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.
"I may be synthetic, but I'm not stupid." -- Bishop 341-B
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.
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.
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
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.
The enemies of Democracy are
Still would be nice to have some links if you could...thanks in advance..
unlike you I actually work in research - specifically involving Alzheimer's, Parkinson's, Autism, and Lipids.
I stand by my statement on mechanisms.
-- Tigger warning: This post may contain tiggers! --
I'm not sure, but I think it may be this drug which treats this form of leukemia. The treatment and the frequency of the type of leukemia both sound right. It was longer ago than I thought, though, since the drug was approved in 2001. That would have put me in college still while the study was going on, so yeah that's probably right.
The enemies of Democracy are
tyvm for your links, i would mod you, but you cant on your own conversations... : (
No problem. I'm really sorry this probably can't help your grandfather since if he had this kind of leukemia he'd already be receiving the treatment. They're always finding new ways to fight cancer, though, so you never know.
The enemies of Democracy are