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Effects of Parkinson's-Disease Mutation Reversed In Cells

Soulskill posted 1 year,30 days | from the flipping-genetic-switches dept.

Medicine 44

An anonymous reader sends this quote from a press release at Eurekalert: "UC San Francisco scientists working in the lab used a chemical found in an anti-wrinkle cream to prevent the death of nerve cells damaged by mutations that cause an inherited form of Parkinson's disease. A similar approach might ward off cell death in the brains of people afflicted with Parkinson’s disease, the team suggested in a study reported online in the journal Cell on August 15 (abstract). ... Mutations that cause malfunction of the targeted enzyme, PINK1, are directly responsible for some cases of early-onset Parkinson’s disease. Loss of PINK1 activity is harmful to the cell’s power plants, called mitochondria, best known for converting food energy into another form of chemical energy used by cells, the molecule ATP. In Parkinson’s disease, poorly performing mitochondria have been associated with the death of dopamine-producing nerve cells in a region of the brain called the substantia nigra, which plays a major role in control of movement. Loss of these cells is a hallmark of Parkinson’s disease and the cause of prominent symptoms including rigidity and tremor. A UCSF team led by Shokat, a Howard Hughes Medical Institute Investigator, used the chemical, called kinetin, to increase mutant PINK1 enzyme activity in nerve cells to near normal levels. 'In light of the fact that mutations in PINK1 produce Parkinson’s disease in humans, the finding that kinetin can speed mutated PINK1 activity to near normal levels raises the possibility that kinetin may be used to treat these patients,' Shokat said."

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Looks promising. (1)

madwheel (1617723) | 1 year,30 days | (#44598005)

This is actually very exciting for me. I have a fairly advanced Lyme disease with other related diseases (protomyxzoa). I have a worry for long term health issues because Lyme is consistently linked to Parkinson's in the long run. Seeing articles like this always give me the hope I've been expecting with modern medicine and technology. Joe

The confusing wordings of TFA (1)

Taco Cowboy (5327) | 1 year,30 days | (#44598165)

Since English isn't my mother tongue, there are times I find myself struggling to understand things others have written.

I have read, and re-read the following, which I copied from TFA:

'In light of the fact that mutations in PINK1 produce Parkinsonâ(TM)s disease in humans, the finding that kinetin can speed mutated PINK1 activity to near normal levels ...'

I dunno about you, but the more times I re-read the above the more confused I got

I do understand the gist of TFA is that the chemical "Kinetin" somehow revived the mitochondria to produce the molecule ATP, and that somehow, delayed or stopped the death of the dopamine-producing nerve cells that had been affected by either the loss of, or the mutation of the PINK1 enzyme

I still having difficulties digesting the exact meaning of the above quoted texts, though

Re:The confusing wordings of TFA (2)

Nidi62 (1525137) | 1 year,30 days | (#44598187)

Since English isn't my mother tongue, there are times I find myself struggling to understand things others have written.

I have read, and re-read the following, which I copied from TFA:

'In light of the fact that mutations in PINK1 produce Parkinsonâ(TM)s disease in humans, the finding that kinetin can speed mutated PINK1 activity to near normal levels ...'

I dunno about you, but the more times I re-read the above the more confused I got

Well, it talks about the mitochondria "perform poorly". My guess is that the mutation somehow slows down the operation of the mitochondria, which would have been linked to Parkinsons. So my takeaway is that the kinetin speeds back up the operation of the mitochondria to close to non-mutated levels. But yes the summary is worded rather poorly.

Re:The confusing wordings of TFA (1)

AmiMoJo (196126) | 1 year,30 days | (#44599177)

I wonder if this could also be used to treat Chronic Fatigue Syndrome. The current best theory on how it works is that the mitochondria are not working properly and so energy is not delivered to the muscles properly.

Of course it will probably be decades before I can benefit from this...

Re:The confusing wordings of TFA (0)

Anonymous Coward | 1 year,29 days | (#44600811)

Kinetin ends up in KTP, which causes PINK1 to be more effective (instead of being on ATP substrate). Sounds as a relatively simple way to address the cause of the disease with a simplistic (and non-patented) chemical.

Re:The confusing wordings of TFA (1)

Anonymous Coward | 1 year,30 days | (#44598375)

They are claiming that mutated PINK1 does its job slower but if you mess with something else it can make mutated PINK1 do its job as fast as nonmutated PINK1 would have done.

Re:The confusing wordings of TFA (0)

Anonymous Coward | 1 year,30 days | (#44598679)

Essentially yes, the enzyme produced from the mutant PINK1 performs poorly, they have found that kinetin can enhance it's activity to nearly normal levels you would see with non mutant PINK1, thus allowing the mitochondria to produce normally.

Re:The confusing wordings of TFA (0)

Anonymous Coward | 1 year,29 days | (#44602049)

It looks like there is a naturally occurring enzyme called Pink1 that is needed in a section of the brain called "substantia nigra" that controls motor functions. Pink1 (like all other cells) needs a chemical called ATP (Adenosine Tri-Phosphate). There is a cycle called krebs cycle that produces a net of 36 ATP every time the cycle is completed. A mutation in Pink1 slows the production of ATP, and the loss of ATP causes damage to the "Substantia Nigra" and this damage shows up as Parkinsons Disease.

Re:The confusing wordings of TFA (0)

Anonymous Coward | 1 year,28 days | (#44606537)

Let me see if I can't clear things up a bit - I know the researchers who did this work well, and have spoken to both recently.

What they found is that kinetin triphosphate, a molecule that looks a lot like ATP (just with a furfuryl group off the top), can be used instead of ATP by PINK1 as a phosphor donor. That by itself is a really cool result, since the ATP binding site for kinases are extremely well conserved, generally. What makes it exciting for Parkinson's Disease is that they discovered that this 'neo-substrate' (as they termed it) can amplify the activity of PINK1 pretty substantially. PINK1's role inside the cell is to drive elimination of broken mitochondria (among some other related things) - and bear in mind that broken mitochondria are probably the most significant source of free radicals in cells, and that they can be potent inducers of programmed cell death (apoptosis). Add to this that dopamine is very toxic to mitochondria, and you can see why some people are excited about the potential for their drug to be a PD therapy.

In their paper, the scientists found that their drug, when given to neurons that had been stressed, meaningfully reduced their rate of apoptosis. They're now moving forward into other models of the disease, and hoping that they can show that in the presence of mitochondrial stress in-vivo, their drug can promote neuron survival.

Wish them luck!

Re:The confusing wordings of TFA (1)

Optali (809880) | 1 year,28 days | (#44616157)

Oh, oh, I read ATP, speeding up and mitochondria... and I can't but think on a new market:

Kinetin supplementation for athletes !!!

Re:Looks promising. (0)

Anonymous Coward | 1 year,30 days | (#44598175)

Good luck with all that.

How's the Morgellons disease progressing?

Re:Looks promising. (1)

philip.paradis (2580427) | 1 year,30 days | (#44598835)

Are you aware that Lyme disease [wikipedia.org] is real, and is frequently difficult to treat unless diagnosed relatively early?

Re:Looks promising. (0)

Anonymous Coward | 1 year,28 days | (#44610091)

I'm well aware of Lyme disease, having known several people who have been treated for it.

I'm always well aware of various other diseases, including mental diseases. Just Google Protomyxzoa. Both Lyme and Protomyxzoa are catch-all diseases that people suffering (whether in actuality or not) from some undiagnosed illness frequently self-diagnose with.

The OP might also think he has Fibromyalgia. I don't doubt that he's suffering from something, just that when people start throwing around terms like Lyme or Protomyxzoa, mental illness should hit your radar.

I knew a guy who had rare genetic disease effecting his ligaments. For years he went from doctor to doctor trying to get a diagnosis, as he was apparently deteriorating neurologically, having severe muscle tremors. But even his own mother (a psychiatrist) thought he was faking it, or had a mental illness. Heck, even I thought that a little bit. But eventually, after 8+ years, he found a specialist who was able to diagnose his disease (I forgot the name, but the crux of it was that his spine was being pulled out of his skull slowly, tearing the fibers), for which he was able to receive treatment and halt the neurological regression.

So... I can understand the pain of having an undiagnosed illness. But despite everything he went through, he never once claimed any particular diagnosis, even though he could have easily told friends he had Lyme disease, as so many other people have.

How can lyme cause dna damage in mitochondria? (1)

Marrow (195242) | 1 year,29 days | (#44599707)

How can lyme disease be at all related to Parkinsons? Are they saying that advanced stage lyme disease has similar symptoms to parkinsons?

Coming soon to theaters (4, Funny)

dkleinsc (563838) | 1 year,30 days | (#44598055)

Back to the Future IV - Great Scott!

Re:Coming soon to theaters (1)

Horshu (2754893) | 1 year,30 days | (#44598261)

My thoughts exactly!

What brand of wrinkle cream? (1)

Anonymous Coward | 1 year,30 days | (#44598077)

I didn't think any of that stuff actually worked. Now to rub some on my brain.....aahhhh. Soothing.

Re:What brand of wrinkle cream? (0)

Anonymous Coward | 1 year,30 days | (#44599003)

"I didn't think any of that stuff actually worked. Now to rub some on my brain.....aahhhh. Soothing."

It does. Your brain will smooth out and you'll be real slick.

Dynamite Plots (0)

Anonymous Coward | 1 year,30 days | (#44598235)

No time to look closer but use of dynamite plots should cause readers to doubt the authors are serious about data analysis.

I have just spent the last half hour studying PD (1)

Macchendra (2919537) | 1 year,30 days | (#44598239)

And I just can't seem to find anything snarky or witty to say about it. :-( Oh Slashdot...

Re:I have just spent the last half hour studying P (0)

Anonymous Coward | 1 year,30 days | (#44598323)

Its easy for any paper these days. Is the following info made obvious:
1) Sample size
2) Distribution of results (not just mean +- whatever)
3) Comparison of effect sizes to "reference group" data from previous studies if available
4) Discussion of the multitude of assumptions made and experiments discarded due to what has been deemed probably accidental deviations from the protocol

Wrinkles (0)

Anonymous Coward | 1 year,30 days | (#44598273)

But if it takes the convolutions (wrinkles) out of my cerebral cortex won't I be stupider?

Virgin coconut oil contains kinetin (2, Informative)

sonamchauhan (587356) | 1 year,30 days | (#44598301)

See this site for some of the benefits of coconut oil: (Parkinson's is mentioned)
http://m.naturalnews.com/news/039388_coconut_oil_dementia_alzheimers_disease.html [naturalnews.com]

Re:Virgin coconut oil contains kinetin (1)

Anonymous Coward | 1 year,30 days | (#44598367)

"This is not just a 'health nut' making these claims - it's all backed by scientific research and touted by many natural healthcare professionals like, Dr. Bruce Fife and Dr. Russell Blaylock."

Oh, well, that puts me at ease. I'm usually pretty skeptical of these things, but there's nothing like a long-winded "trust me" to quell my concerns.

Re:Virgin coconut oil contains kinetin (0)

Anonymous Coward | 1 year,30 days | (#44598423)

If I had this, I would take injectable glutathione and alpha-lipoic-acid until I glowed bluer than a hindu god.

Re:Virgin coconut oil contains kinetin (4, Interesting)

pnagel (107544) | 1 year,30 days | (#44598779)

This comment is actually much more relevant to the OP than it may seem.

As the OP says, Parkinsonson's is essentially a fuel crisis of the brain due to impaired mitochondrial function.

One way to fix this would be to repair the mitochondrial function, as the OP article tries to.

But another way would be to find an alternative fuel source for the brain.

Those who promote coconut oil point of that it it specifically the metabolism of glucose that is impaired in Parkinson's (hence the modern trend of calling it Type III Diabetes). But there are many other energy substrates used my mitochondria, and ketones is one type that brain cells can also make use of.

Coconut oil is high in MCTs (medium-chain triglycerides), which have the unique property of being immediately converted to ketones in the liver. Thus the point of the coconut oil is to give the starving brain something else to run on.

Another way to raise ketones is by using a ketogenic diet (hence the name), as was the standard effective treatment for epilepsy early last century before drugs became available (and ketogenic diets have been making a comeback as alternative treatment when drugs don't help).

In a ketogenic diet, the vast majority of one's energy is derived from fat sources, not carbohydrates. As a side effect of metabolising fat for energy all over the body, ketones are released at a much higher level than otherwise, and these ketones themselves are then available as fuel for the brain (and other tissues).

Atkins for Parkinson's (1)

tepples (727027) | 1 year,29 days | (#44600155)

Another way to raise ketones is by using a ketogenic diet (hence the name)

How close is the ketogenic diet to an Atkins style low carbohydrate diet?

Re:Atkins for Parkinson's (4, Interesting)

pnagel (107544) | 1 year,29 days | (#44600299)

The induction phase of the Atkins diet is mostly a ketogenic diet. For the treatment of epilepsy, there are now a handful of variations on the original ketogenic diet used since the 1920s, one of these is known as the "Modified Atkins" [charliefoundation.org] .

However, there are stricter metabolic goals when on a ketogenic diet and special things to watch out for (too much protein can knock one out of ketosis, for example), so it is best to approach a ketogenic diet as a specialty topic in its own right rather than as something that a different low-carb diet may or may not achieve as a side effect.

There is a lot of recent research on the neuroprotective properties of a ketogenic diet, not just for Alzheimer's, but also for Parkinsons and stroke. See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2367001/ [nih.gov] for example.

"shows potential"... "promising"... "possibly". (2)

mark-t (151149) | 1 year,30 days | (#44598513)

In other words... they don't *actually* have any good news. They're just particularly hopeful that they will.

Sounds like somebody is using a particularly optimistic phrasing in order to get funding for more research.

Not to belittle such research, but until that research actually bears real fruit, it feels to me like they are deliberately trying to mislead people into thinking that a practical cure or treatment is basically here already (even though they don't actually come right out and say so), and to me that's not any better than the conmen who travelled from village to village in the 1700's selling "snake oil".

Re:"shows potential"... "promising"... "possibly". (1)

jeffb (2.718) (1189693) | 1 year,29 days | (#44599721)

No, in other words, they're being responsible and cautious in their claims.

Are you really clamoring for more press releases that trumpet a "breakthrough" or a "cure"? It seems to me that we get plenty of those already, and I, for one, am pretty sick of them.

Re:"shows potential"... "promising"... "possibly". (1)

mark-t (151149) | 1 year,29 days | (#44600435)

Actually, I'd just appreciate if they were just a whole lot more up front about the fact that they haven't actually verified any of their hypotheses yet. They dance around this using what seems to be carefully chosen verbiage that reminds me all too much of people who try to twist the truth to make things sound better than they actually are, but don't want to get caught in any actual outright lie. Is forthright honesty really too much to expect from people?

Re:"shows potential"... "promising"... "possibly". (1)

cjjjer (530715) | 1 year,29 days | (#44599883)

You realize that this is the basis of all large scale research funding?

Water snake oil vs. VapoRub/Capzasin (1)

tepples (727027) | 1 year,29 days | (#44600303)

to me that's not any better than the conmen who travelled from village to village in the 1700's selling "snake oil".

The con men were themselves conned. There's one snake whose oil does in fact provide some of the benefits that were claimed for snake oil: Enhydris chinensis, the Chinese water snake. But too many snake oil peddlers were under the impression that any snake would work, which is where snake oil got its bad reputation. And then there was Clark Stanley's snake oil based on a Hopi recipe, which worked (it was similar to modern capsaicin and camphor rubs) but was ruled as mislabeled because it didn't come from a snake at all.

"a chemical found in an anti-wrinkle cream" (1)

someone1234 (830754) | 1 year,30 days | (#44598611)

What? Is that the first occurence of the chemical? I mean, the scientists just tested several cosmetics to look for a useful chemical? In the past, scientists looked for useful chemicals in plants or even designed them. Now they 'find' useful chemicals in products.

Re:"a chemical found in an anti-wrinkle cream" (1)

pspahn (1175617) | 1 year,30 days | (#44598915)

Few things drive science forward more than the need for French designed anti-aging skin products.

If women weren't so vain, we'd still be stuck in 1820.

Re: "a chemical found in an anti-wrinkle cream" (0)

Anonymous Coward | 1 year,29 days | (#44601739)

Speaking of women, and since it was UCSF, anyone know if any of this research used human embryonic stem cells? (Which exploits young women, hence my initial comment.)

Energy-restoring protoocols are effective for many (3, Informative)

Eukariote (881204) | 1 year,30 days | (#44598687)

This is not the first time that a protocol that restores energy metabolism, or protects it, has been found effective. And not just in early-onset Parkinson's. See for example the work of Birkmeyer [google.com] who developed a protocol around NADH and Co-enyme Q10 (both co-enzymes active in glucose metabolism). Or the use of coconut oil [undergroun...porter.com] (for the lauric acid contained therein) as a dietary addition to provide ketones as an alternative for glucose to energize cells: also found effective for many Alzheimers patients.

The ketogenic approach is easy to try as coconut oil is readily available. The Birkmeyer protocol requires a few supplements, in particular stablized NADH to be taken on an empty stomach.

Great Scott! (1, Funny)

Totenglocke (1291680) | 1 year,30 days | (#44598877)

I'm sure Michael J. Fox heard the news and started quivering in anticipation.

Anti-wrinkle cream boost sales (0)

Anonymous Coward | 1 year,30 days | (#44599281)

Great, you just gave the anti-wrinkle cream makers a new tagline:
Removes wrinkles and reverses Parkinson's disease!

Bad Elsevier; bad, bad, bad (1)

damn_registrars (1103043) | 1 year,29 days | (#44599919)

This article is so highly paywalled I have tried to access it from two large public research universities and neither of them has access to this yet even though they subscribe to Cell. They want the same $31.50 for the article from those universities as they want from anyone else.

More treating. (0)

Anonymous Coward | 1 year,29 days | (#44603641)

Less talk.

Common claim (1)

vrhino (2987119) | 1 year,29 days | (#44604875)

Every month this sort of article comes out. Maybe they are getting close. Somebody is going to get the cure or the vaccine but today the best treatment for humans is levadopa and that drug is from the 1950s. There are lots of things that can treat PD in a mouse or a monkey but for people, not so much. Although injection of Ganglioside GM-1 had a successful clinical trial.

Oh great... (1)

concurrent.ca (909690) | 1 year,28 days | (#44608571)

...isn't this exactly the sort of research that destroyed Raccoon City?
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