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-   -   So which "existing" diabetes drug turns the PGC-1 Alpha "Master Switch" back on? (https://www.neurotalk.org/parkinson-s-disease/134572-existing-diabetes-drug-pgc-1-alpha-master-switch.html)

caldeerster 10-06-2010 09:03 PM

So which "existing" diabetes drug turns the PGC-1 Alpha "Master Switch" back on?
 
Possibly this one?

http://jap.physiology.org/cgi/content/full/101/6/1685

Metformin increases the PGC-1 protein and oxidative enzyme activities possibly via AMPK phosphorylation in skeletal muscle in vivo

http://en.wikipedia.org/wiki/Metformin

Conductor71 10-06-2010 09:24 PM

Good question
 
Quote:

Originally Posted by caldeerster (Post 702160)
Possibly this one?

http://jap.physiology.org/cgi/content/full/101/6/1685

Metformin increases the PGC-1 protein and oxidative enzyme activities possibly via AMPK phosphorylation in skeletal muscle in vivo

http://en.wikipedia.org/wiki/Metformin

I am thinking this class of drugs:

Thiazolidinediones one of which is Pioglitazone which I remembered seeing that it was a diabetic drug that held promise for treating Parkinson's

Here is an article on it from 2006


I find it interesting that we have an endocrine link...who is it here that strongly feels PD is linked to insulin metabolism...is it Bluedhalia?

Laura

caldeerster 10-06-2010 09:51 PM

Thanks for the link
 
That was four years ago. Have they started a trial yet?


Quote:

Originally Posted by Conductor71 (Post 702165)
I am thinking this class of drugs:

Thiazolidinediones one of which is Pioglitazone which I remembered seeing that it was a diabetic drug that held promise for treating Parkinson's

Here is an article on it from 2006


I find it interesting that we have an endocrine link...who is it here that strongly feels PD is linked to insulin metabolism...is it Bluedhalia?

Laura


Conductor71 10-06-2010 10:13 PM

We're talking the world of research alternate universe
 
Quote:

Originally Posted by caldeerster (Post 702174)
That was four years ago. Have they started a trial yet?

Yep, that's why I wondered whether this was just old but updated news which essentially it is. Researchers were onto this four years go, but I guess the genetic link and the master switch thing are the key new developments.

The brand name is Actos. I guess this is one of the few that doesn't have nasty cardiac side effects. There is a really great article in Nature on all of this. You'll love this quote:

... a clinical trial to test Actos in patients with Parkinson's disease has already been approved by regulators.

Nature article

No trial to date that I can find at clinicaltrials.gov

Laura

caldeerster 10-06-2010 10:20 PM

I looked there too
 
Couldn't find anything.

There is a new trial of Byetta (another Diabetes drug) that is taking place in England. But I don't know if it stimulates this particular protein.

The link you provided says that MJFF provided some funding for the study. I don't get why four years have gone by without a trial.

Cal


Quote:

Originally Posted by Conductor71 (Post 702179)
Yep, that's why I wondered whether this was just old but updated news which essentially it is. Researchers were onto this four years go, but I guess the genetic link and the master switch thing are the key new developments.

The brand name is Actos. I guess this is one of the few that doesn't have nasty cardiac side effects. There is a really great article in Nature on all of this. You'll love this quote:

... a clinical trial to test Actos in patients with Parkinson's disease has already been approved by regulators.

Nature article

No trial to date that I can find at clinicaltrials.gov

Laura


paula_w 10-08-2010 09:25 AM

Published online 6 October 2010 | Nature | doi:10.1038/news.2010.518

News
Damaged cell powerhouses linked to Parkinson's
New uses for old drugs

Such drugs have already been widely pursued as potential therapies for type 2 diabetes, and some have already been approved for that use. Avandia (rosiglitazone), a diabetes drug recently pulled from the European market because it raises the risk of heart attack, activates a key protein in the PGC-1α pathway.

But a related drug called Actos (pioglitazone) has not been firmly linked to heart attack and remains in use. Beal says that a clinical trial to test Actos in patients with Parkinson's disease has already been approved by regulators.

http://www.nature.com/news/2010/1010....2010.518.html

no mention of metformin altho it sounds safe for diabetes.

Conductor71 10-08-2010 11:21 AM

What happened to it?
 
Quote:

Originally Posted by paula_w (Post 702624)

But a related drug called Actos (pioglitazone) has not been firmly linked to heart attack and remains in use. Beal says that a clinical trial to test Actos in patients with Parkinson's disease has already been approved by regulators.

http://www.nature.com/news/2010/1010....2010.518.html

no mention of metformin altho it sounds safe for diabetes.

Paula,

We're onto that, but Actos was first brought up in the news four years ago! MFJJ funded the initial study and there has been no movement on it. I searched for the lead researchers name "Marina Emborg" and it doesn't even look like it is on her radar...another possible major treatment sucked into the black hole.

If Debi Brooks is reading...help! :)

Laura

caldeerster 10-08-2010 04:21 PM

I second that - Debi Brooks can you give us an update? TIA!
 
Thanks Laura

Cal

Quote:

Originally Posted by Conductor71 (Post 702661)
Paula,

We're onto that, but Actos was first brought up in the news four years ago! MFJJ funded the initial study and there has been no movement on it. I searched for the lead researchers name "Marina Emborg" and it doesn't even look like it is on her radar...another possible major treatment sucked into the black hole.

If Debi Brooks is reading...help! :)

Laura


paula_w 10-08-2010 08:18 PM

emailed
 
...debi brooks and katie hood; hope they know, could it possibly be under wraps? Does it involve a separate patent?

villiers 10-09-2010 06:06 AM

it seems cinnamon & extra virgin coconut oil supplementation might do the job as good as a diabete drug concerning the PGC-1 Alpha
Alzeihmer is considered more&more as a diabete type 3 (cognitive diabete)
i invite you to read this !!!!!!!!!!!!

coconut oil
http://alzheimers.infopop.cc/eve/for...261/m/63910335

cinnamon
http://alzheimers.infopop.cc/eve/for...1/m/6051008062

reverett123 10-09-2010 08:58 AM

My money is betting that they are talking about Exendine-4 that Tom Isaacs is flogging gila monsters to produce. I found a corporate presentation for investors from early this year at pharmain.com/pdfs/Non-ConfidentialTechnologyPresentation.pdf

Download and look at the last three or four pages. Among other interesting tid bits are "PGC protects GLP-1 from DPP-IV degradation". That is exactly what Tom and crew are into. GLP-1 is the peptide that rebuilds the brain and DPP-IV is the enzyme that prevents it from working.

lurkingforacure 10-09-2010 09:23 AM

I read this also
 
Quote:

Originally Posted by villiers (Post 702909)
it seems cinnamon & extra virgin coconut oil supplementation might do the job as good as a diabete drug concerning the PGC-1 Alpha
Alzeihmer is considered more&more as a diabete type 3 (cognitive diabete)
i invite you to read this !!!!!!!!!!!!

coconut oil
http://alzheimers.infopop.cc/eve/for...261/m/63910335

cinnamon
http://alzheimers.infopop.cc/eve/for...1/m/6051008062

Yep, I read about the connection between Alz. and diabetes some time ago, glad to see others are looking into this as well. And I have also read that the coconut oil helps with other dementias, not just Alz. Rick posted a thread about a gentleman taking coconut oil who was improving cognitively, so there is definitely something to that oil. I've also read it helps with constipation, FYI.

paula_w 10-09-2010 09:42 AM

received a reply
 
From Katie Hood in part: "I know we've led a lot of work on pioglitazone in PD. what's exciting is that we just launched/are launching a new "repurposing" RFA - meant to specifically fund work to show that drugs developed for other diseases might help PD. $3M i believe. so work like this has a way to get funded!"

From Todd Sherer: "Just for more information, based on work supported
by the MJFF, the NIH has awarded funding for a clinical trial on
pioglitazone that is scheduled to start early next year."

Thanks to you both for responding!

caldeerster 10-09-2010 01:35 PM

That's good news
 
Thanks for that, Paula.

The ongoing exendin trial in the UK may provide some answers as well. Is anyone here participating in that trial or knows someone who is?



Quote:

Originally Posted by paula_w (Post 702955)
From Katie Hood in part: "I know we've led a lot of work on pioglitazone in PD. what's exciting is that we just launched/are launching a new "repurposing" RFA - meant to specifically fund work to show that drugs developed for other diseases might help PD. $3M i believe. so work like this has a way to get funded!"

From Todd Sherer: "Just for more information, based on work supported
by the MJFF, the NIH has awarded funding for a clinical trial on
pioglitazone that is scheduled to start early next year."

Thanks to you both for responding!


Conductor71 10-09-2010 08:57 PM

This sounds even better
 
Quote:

Originally Posted by reverett123 (Post 702946)
My money is betting that they are talking about Exendine-4 that Tom Isaacs is flogging gila monsters to produce. I found a corporate presentation for investors from early this year at pharmain.com/pdfs/Non-ConfidentialTechnologyPresentation.pdf

Download and look at the last three or four pages. Among other interesting tid bits are "PGC protects GLP-1 from DPP-IV degradation". That is exactly what Tom and crew are into. GLP-1 is the peptide that rebuilds the brain and DPP-IV is the enzyme that prevents it from working.

Wow. Hadn't heard of this potential treatment. Tom must be doing something right; it looks like clinical trials (pilot study) on Exendin-4 for PD is now recruiting participants in the UK. This would move through FDA hoops so much the sooner.

Exendin-4 as a Treatment for Parkinson's

lurkingforacure 10-10-2010 01:07 PM

what about cogane?
 
Quote:

Originally Posted by reverett123 (Post 702946)
My money is betting that they are talking about Exendine-4 that Tom Isaacs is flogging gila monsters to produce. I found a corporate presentation for investors from early this year at pharmain.com/pdfs/Non-ConfidentialTechnologyPresentation.pdf

Download and look at the last three or four pages. Among other interesting tid bits are "PGC protects GLP-1 from DPP-IV degradation". That is exactly what Tom and crew are into. GLP-1 is the peptide that rebuilds the brain and DPP-IV is the enzyme that prevents it from working.

I thought Isaacs headed up the Cure PD Trust over there which was claiming Cogane was the "cure" for PD we have al been waiting for?....but not really, if he is really working on this? What does this say about Cogane, which is to start trials here in the US early next year?

reverett123 10-10-2010 04:57 PM

Tom and the Trust are miniature versions of MJFF and raise funds for multiple studies.


Quote:

Originally Posted by lurkingforacure (Post 703215)
I thought Isaacs headed up the Cure PD Trust over there which was claiming Cogane was the "cure" for PD we have al been waiting for?....but not really, if he is really working on this? What does this say about Cogane, which is to start trials here in the US early next year?


paula_w 10-10-2010 10:23 PM

Again
 
Quote:

Originally Posted by reverett123 (Post 703252)
Tom and the Trust are miniature versions of MJFF and raise funds for multiple studies.

let's keep it going i need more information - is that ok? i have a good feeling about this.


paula

TommyI 10-11-2010 04:00 PM

Sorry all. Been ill since wpc and trying to catch up.

For the record neither I nor anyone else at CPT has ever said Cogane will be the "cure" for Parkinson's. We continue to be excited about the product and our support of it assisted the pharma company which owns it in securing funding to the tune of £25million. Without our support the product might never have made it to clinical trial - so feel rather disgruntled about negative comments, but perhaps I misread them and no matter anyway. Just wanted to get that straight. No need for further comment.

Exendin - yes - it's looking more and more exciting particularly in view of articles which I am forwarding to Rick as I don't know how to attach them here. PIlot study has started a Queen Square in LOndon. Will keep you posted.

Tom

paula_w 10-12-2010 07:15 AM

hope you're feeling better
 
It's no wonder you came down with something. What a job it must have been to pull that off! We enjoyed it and see you have a very nice group working with you. It was a wonderful place to hang out but i thihk each wii machine has their own 'slant' as my bowling was terrible and i'm pretty decent at home.

:winky:

reverett123 10-13-2010 09:09 PM

Those following this subject might find this of interest.
http://onlinelibrary.wiley.com/doi/1...10.00090.x/pdf

VICTORIALOU 10-16-2010 06:58 PM

actos
 
Quote:

Yep, that's why I wondered whether this was just old but updated news which essentially it is. Researchers were onto this four years go, but I guess the genetic link and the master switch thing are the key new developments.
The brand name is Actos. I guess this is one of the few that doesn't have nasty cardiac side effects. There is a really great article in Nature on all of this. You'll love this quote:
... a clinical trial to test Actos in patients with Parkinson's disease has already been approved by regulators.
No trial to date that I can find at clinicaltrials.gov

Thanks for including the "Nature" article.
If I was reading it correctly, the regulators, referred to in the article, are in Europe. So perhaps there is a trial going on there.
I am definitely going to look into Actos after seeing the Science Daily article today on research from Harvard.

AmyStanford 07-13-2011 11:23 AM

PGC-1 activation causes severe side effects
 
It would be important to realize that activation of PGC-1 {alpha} and {beta} has severe side effects that can occur during a treatment:

Below a summary about the possible problems:
- When PGC-1 {alpha} or {beta} are higher in the muscle, tumor necrosis factor {alpha} (TNF {alpha}) is elevated. More TNF {alpha}, a mediator of inflammation, is secreted into the blood (cf. Olesen J et al; Medicine & Science in Sports & Exercise: October 2010 - Volume 42 - Issue 10 - p 58.
- The same article shows this at basal levels and that it worsens following injection of TNF into muscle.
- When PGC-1 is elevated more lipids are accumulating in muscle. People can become obese. Lipids often induce inflammation (cf. Summermatter S et al; Journal of biological chemistry: October 2010 22;285(43):32793-800)
- Then PGC-1 can even induce diabetes when too high (cf. Miura S, Journal of biological chemistry: August 2003 15;278(33):31385-90.)
- High PGC-1 {alpha} and {beta} levels, basal and after stimulation by TNF or Lipopolysaccharide (LPS) lead to high expression and release of inflammatory IL (interleukin) and of macrophage infiltration as indicated by CD (cluster of differentiation)

All this should be kept in mind. Maybe it's still ok to develop drugs that promote PGC-1, but it should be considered that this can have these side effects.


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