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."

Re:I don't know

[Anonymous Coward]

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:Hmm, how safe is safe enough?

[jrmcc]

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:huh?

[icebike]

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:Hmm, how safe is safe enough?

[ColdWetDog]

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:I don't know

[swanzilla]

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:Skepticism may be warranted, here.

[smellsofbikes]

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:Hmm, how safe is safe enough?

[afidel]

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?

Cure, eh?

[TheModelEskimo]

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:How do they calculate the time needed

[PotatoFarmer]

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:Hmm, how safe is safe enough?

[Caged]

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:Cure, eh?

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

Re:Hmm, how safe is safe enough?

[Qzukk]

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.

Here's the abstract:

[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 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.

Re:Hmm, how safe is safe enough?

[afidel]

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:I don't know

[noundi]

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.

pardon me?

[Anonymous Coward]

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

Re:Cure, eh?

[mea37]

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.