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.
'Once we find the compound, we need to make sure it’s safe. ... says Kanthasamy."
This is not quite doing it for me.
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.
http://www.storz-bickel.com/vaporizer/volcano-vaporization-system.html
the only true therapy with any real benefit.
... 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?
Finally, M.J.Fox can make Back To The Future 4 !
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!
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.
"10 years" and "major breakthrough"? Somethind doesn't add up here.
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! --
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?
http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/SpeedingAccesstoImportantNewTherapies/ucm128291.htm
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.
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
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
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.
-- Tigger warning: This post may contain tiggers! --