Gas6?

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Cobblestones said:
I don't agree, because they're only looking at acute anemia in WT. What they would need is a model for chronic anemia with WT. There will be some physiological adjustment to the chronic anemia which might be exploited.
As I said, more representative. Got to work with what we have!
 
May 13, 2009
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King Boonen said:
As I said, more representative. Got to work with what we have!
And I maintain that neither is representative.

What seems not disputed is the effect of a combined treatment following acute anemia (caused by extracting a pint or so for refill day).

Maybe the bilharzia thing is just a red herring in that story and the EPO (+GAS6)-assisted autologous transfusion thing is all the explanation which is needed, however it certainly looks like an odd coincidence.
 
Sep 25, 2009
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based on a single study of Angelillo-Scherrer et al, i am trying to figure out if Gas6 has the potential as a doping agent

let's look at several groups to understand the applicability

1. A healthy, non anemic adult -Hct=45% with some fluctuations due to a life style (elevation, diet etc). When given EPO, easily responds by raising hct above 50%. not the subject of the study.

2. Anemic adult - Hct-30%. May or may not respond to EPO (for ex, 50% of cancer patients don’t respond). not the subject of the study.

3. A healthy professional rider, good EPO responder - Hct=42%. hct easily pushed to over 50%. not the subject of the study.

4. Anemic mouse, non-responsive to EPO alone (a case similar to humans in para. 2). not THE subject of the study.


5. Anemic, epo-alone non-responsive mouse that responds when epo was co-administered with Gas6. the subject of the study.

let's entertain how a healthy professional athlete can become a sick mouse that does not respond to epo alone ?

Simple. from the study: he/she has to:
- make rbc where humans don’t - the spleen.
- possess a pathology that results in anemia (cancer or excessive rbc destruction for whatever cause etc…)
- be an epo doper to begin with

To achieve a purely theoretical possibility of having the mouse study apply to a pro rider we must assume that he would benefit from gas6 ONLY if he was anemic AND a poor epo responder, natural or exogenous, does not matter. Fair enough, no medic would be surprised if a poor epo responder becomes anemic. right ?

but here is the first problem. how would a rider become an elite endurance pro if he is lacking the key precondition of any elite performance - having a healthy rbc reproduction in the first place? Well, the clinic expert might retort, 'he consumed mega doses of epo or transfused own or someone’s blood all along…'

this brings us to the second problem - the precondition for Gas6 effectiveness is presence of epo, which means he doped with both epo and gas6 since being a junior.

this is a catch 22 game. needless to point to the absurdity of such logic. But as a clinic topic it is perfect.
 
taiwan said:
Agree it's an interesting thread, but I'm clearly no experts. Posters with (genuine ;)) specialised knowledge would be very welcome to keep the thread realistic.
Yes, a very interesting thread, especially in the last few pages. Thanks.

So the discussion of the effects of the Biharzia a few pages back suggest an interesting ethical question:

If (for the sake of this particular argument) you give Froome the benefit of the doubt in terms of intentional doping, but it turns out the annual biharzia treatment prompts a physiological response that confers him a doping-like benefit (the hypothesis being the treatment stimulates low level natural epo) should he (or some future sufferer) be allowed to race at all? I'm tending to think (if it was the case that the treatment has a 'doping' effect outside the immediate treatment of the parasite) that he shouldn't - otherwise you might create a bizarre incentive for riders to seek out a parasite in order to use the treatment (or maybe just because I want Contador to win . . .)

Apologies if this has been discussed elsewhere - I've lost track of the clinic over the last few months.
 
May 13, 2009
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python said:
based on a single study of Angelillo-Scherrer et al, i am trying to figure out if Gas6 has the potential as a doping agent

let's look at several groups to understand the applicability

1. A healthy, non anemic adult -Hct=45% with some fluctuations due to a life style (elevation, diet etc). When given EPO, easily responds by raising hct above 50%. not the subject of the study.

2. Anemic adult - Hct-30%. May or may not respond to EPO (for ex, 50% of cancer patients don’t respond). not the subject of the study.

3. A healthy professional rider, good EPO responder - Hct=42%. hct easily pushed to over 50%. not the subject of the study.

4. Anemic mouse, non-responsive to EPO alone (a case similar to humans in para. 2). not THE subject of the study.


5. Anemic, epo-alone non-responsive mouse that responds when epo was co-administered with Gas6. the subject of the study.

let's entertain how a healthy professional athlete can become a sick mouse that does not respond to epo alone ?

Simple. from the study: he/she has to:
- make rbc where humans don’t - the spleen.
- possess a pathology that results in anemia (cancer or excessive rbc destruction for whatever cause etc…)
- be an epo doper to begin with

To achieve a purely theoretical possibility of having the mouse study apply to a pro rider we must assume that he would benefit from gas6 ONLY if he was anemic AND a poor epo responder, natural or exogenous, does not matter. Fair enough, no medic would be surprised if a poor epo responder becomes anemic. right ?

but here is the first problem. how would a rider become an elite endurance pro if he is lacking the key precondition of any elite performance - having a healthy rbc reproduction in the first place? Well, the clinic expert might retort, 'he consumed mega doses of epo or transfused own or someone’s blood all along…'

this brings us to the second problem - the precondition for Gas6 effectiveness is presence of epo, which means he doped with both epo and gas6 since being a junior.

this is a catch 22 game. needless to point to the absurdity of such logic. But as a clinic topic it is perfect.
Not quite.

They did check for the spleen/BM thing by surgically removing the spleen. Still works with BM.

Parasites feasting on RBCs is considered a pathology resulting in anemia.

An EPO doper to begin with? Not necessary

Need to be a poor EPO responder? Not necessary, he may be compared to the control group if applicable. Remember anemia =/= poor EPO responder

Became an elite endurance pro despite bilharzia? That's the story fed to us by Sky. Fact is, he is an elite endurance pro now. He might suffer (might have suffered up to a point in time) from bilharzia. If there was an overlap in time, I don't know. Maybe it's crap like the Danielse-Eskimo-gluten BS.

Presence of EPO: there's nothing indicating that he doesn't produce sufficient EPO. In fact, I have argued repeatedly that he's possibly producing more EPO precisely because of his disease.

Perfect clinic topic? Clearly YMMV
 
Weight Loss

Role of Gas-6 in Adipogenesis and Nutritionally Induced Adipose Tissue Development in Mice
Objective— A potential role of growth arrest-specific gene 6 (Gas-6) in energy storage in adipose tissue was investigated in murine models of obesity...
Conclusions— Gas-6 enhances the accumulation of adipose tissue in diet-induced obese mice....

Altogether, these observations suggest that Gas-6 belongs to a class of molecules that are redundant for normal homeostasis, but critical for stress responses. Not surprisingly, inactivation or malfunctioning of such genes does not necessarily cause life-threatening developmental defects but may significantly modulate the severity of disease-related phenotypes such as thrombosis4 and obesity.
http://atvb.ahajournals.org/content/25/5/1002.full?sid=78cd3039-0298-4d64-be32-fb3f3afdab11

Experiments with mice fed a high-fat diet indicated that overexpression of Gas6/TAM signaling might enhance body-fat accumulation, but blocking the system could reduce body-fat mass and body weight
http://jcem.endojournals.org/content/98/2/E267.full

So it also has a major role in obesity ?
 
Feb 8, 2013
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King Boonen said:
Stimulates recoveries, not overproduction. That's why I think it's perfectly reasonable to suggest it could be used as a recovery


So, in conclusion, and this is all based on one study in mice, which is kind of important;

if Froome were a non-responder to EPO, treatment with Gas6+EPO would have less effect than treating an EPO-responder with EPO only.

The research seems to show little to no benefit in combination treatment of Gas6 and EPO for healthy individuals. The lack of much information on this also indicates these findings.

Gas6 treatment aids recovery of hematocrit in both healthy and EPO non-responders, but this recovery is back to baseline. So it has a possible use as recovery aid
King Boonen said:
Based on the evidence in the paper, it's pretty useless for doping except to help non-responders get some boost from EPO.
Yea I pretty much agree with what you've said, from the (limited) evidence doesn't look like gas6 (alone at least) is the answer for froome. The idea of it as a recovery aid from extraction is interesting though...

In the absence of any human studies its hard to know exactly what it's effect wold be

What intrigues me most is what Frei knows about this - with hardly any published research about gas6 it's pretty cutting edge stuff (expensive too btw!).. Has he been dabbling in biochem in his 'break' or is he aware about it from being a pro...? Assume the latter is more likely

King Boonen said:
This is really beyond my biological level but I don't believe that would work. Gas6 is produced at the cellular level so I think it would have to be intravenously administered.
In general proteins can definitely be administered SC, and that's usually preferred too,
 
Dec 14, 2012
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Possible mechanism of action and use: Everyone has a certain basal level of EPO floating around in the system, this level is pretty stable of course as it relates to the oxygen tension at the kidneys. EPO is needed as a signal for erythroblasts to terminally differentiate into mature RBC's.

GAS6 allows erythroblasts to be more sensitive the EPO, thus requiring a lower level of natural EPO to grow up to mature RBC's. The point is that if you could naturally increase EPO, altitude training, you will eventually achieve a higher Red blood cell volume with a smaller drop in the retic count, beating the passport.

My theory.
 
Jul 28, 2009
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taiwan said:
Agree it's an interesting thread, but I'm clearly no experts. Posters with (genuine ;)) specialised knowledge would be very welcome to keep the thread realistic.
To a scientist this is a pretty fun thread. Unlike some other spoilsport 'scientists' on this forum I'm more than happy for you guys to go for it. Why dampen your enthusiasm :D
 
May 26, 2011
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sugarman said:
Yea I pretty much agree with what you've said, from the (limited) evidence doesn't look like gas6 (alone at least) is the answer for froome. The idea of it as a recovery aid from extraction is interesting though...

In the absence of any human studies its hard to know exactly what it's effect wold be

What intrigues me most is what Frei knows about this - with hardly any published research about gas6 it's pretty cutting edge stuff (expensive too btw!).. Has he been dabbling in biochem in his 'break' or is he aware about it from being a pro...? Assume the latter is more likely


In general proteins can definitely be administered SC, and that's usually preferred too,
Spot on - that's what i want to know.....
 
Aug 18, 2009
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python said:
based on a single study of Angelillo-Scherrer et al, i am trying to figure out if Gas6 has the potential as a doping agent

let's look at several groups to understand the applicability

1. A healthy, non anemic adult -Hct=45% with some fluctuations due to a life style (elevation, diet etc). When given EPO, easily responds by raising hct above 50%. not the subject of the study.

2. Anemic adult - Hct-30%. May or may not respond to EPO (for ex, 50% of cancer patients don’t respond). not the subject of the study.

3. A healthy professional rider, good EPO responder - Hct=42%. hct easily pushed to over 50%. not the subject of the study.

4. Anemic mouse, non-responsive to EPO alone (a case similar to humans in para. 2). not THE subject of the study.


5. Anemic, epo-alone non-responsive mouse that responds when epo was co-administered with Gas6. the subject of the study.

let's entertain how a healthy professional athlete can become a sick mouse that does not respond to epo alone ?

Simple. from the study: he/she has to:
- make rbc where humans don’t - the spleen.
- possess a pathology that results in anemia (cancer or excessive rbc destruction for whatever cause etc…)
- be an epo doper to begin with

To achieve a purely theoretical possibility of having the mouse study apply to a pro rider we must assume that he would benefit from gas6 ONLY if he was anemic AND a poor epo responder, natural or exogenous, does not matter. Fair enough, no medic would be surprised if a poor epo responder becomes anemic. right ?

but here is the first problem. how would a rider become an elite endurance pro if he is lacking the key precondition of any elite performance - having a healthy rbc reproduction in the first place? Well, the clinic expert might retort, 'he consumed mega doses of epo or transfused own or someone’s blood all along…'

this brings us to the second problem - the precondition for Gas6 effectiveness is presence of epo, which means he doped with both epo and gas6 since being a junior.

this is a catch 22 game. needless to point to the absurdity of such logic. But as a clinic topic it is perfect.
rata de sentina said:
To a scientist this is a pretty fun thread. Unlike some other spoilsport 'scientists' on this forum I'm more than happy for you guys to go for it. Why dampen your enthusiasm :D
So you agree with python?
 
May 13, 2009
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Alex76 said:
Spot on - that's what i want to know.....
I'd hope the clinicians with connections to the race scene could chime in on that. Without Frei, I wouldn't care much about the stuff. It's one in thousands of studies on experimental stuff which might be construed to possibly give an advantage (hopefully without killing the subject first). With Frei, it becomes something else entirely (unless, of course, Frei got it from this thread in which case everything disappears in a pleasant **** of circular reasoning). Just think this thread had 5 posts in 2 years, then, after Frei's comment there's 15 pages in one day.

ETA: what's wrong with the word ****?
 
Sep 25, 2009
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i was not
Cobblestones said:
Not quite.

They did check for the spleen/BM thing by surgically removing the spleen. Still works with BM.

Parasites feasting on RBCs is considered a pathology resulting in anemia.

An EPO doper to begin with? Not necessary

Need to be a poor EPO responder? Not necessary, he may be compared to the control group if applicable. Remember anemia =/= poor EPO responder

Became an elite endurance pro despite bilharzia? That's the story fed to us by Sky. Fact is, he is an elite endurance pro now. He might suffer (might have suffered up to a point in time) from bilharzia. If there was an overlap in time, I don't know. Maybe it's crap like the Danielse-Eskimo-gluten BS.

Presence of EPO: there's nothing indicating that he doesn't produce sufficient EPO. In fact, I have argued repeatedly that he's possibly producing more EPO precisely because of his disease.

Perfect clinic topic? Clearly YMMV
i was not looking into the froome pathology specifically, rather a general case for gas6 having the potential as a doping agent for most/any pro rider...how many are truly anemic and compete at the highest elite endurance level at the same time ? of course, am not referring to a sports pseudo anemia due to plasma expansion found in most endurance athlete.

as for froome, yes, his case lends itself to gas6 doping easier, but even here there are many questions.

the way i understood the gas6 biochemical role, it acts as a guardian of homeostasis, as a co-factor, that is, normalizing and optimizing cells normal functions when present or impairing them when insufficient or absent.

a theoretical case can be made, that pro riders are in a constant mild state of anemia due to training loads thus elevating their rbc turnover and stimulating their natural epo production. though quite plausible, this scenario need several qualifiers before the gas6 effect can be translated into tangible performance increases in humans.

as to fun part of the clinic speculation, i am all for reading it, as opposed to being an active contributor. not my style.
 

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