Doping Technology 2014

[DirtyWorks]

Thanks again to Dr. veloclinic, I found some very informative, newly published, research.

I don't pretend to know what every term means, but some things are confirmed.

Unsurprisingly, this has resulted in the suspected and proven misuse of a wide range of peptide hormones and substances such as insulin, insulin-like growth factor 1, human growth hormone (hGH), epoetins, chorionic gonadotrophins, gene doping substances including RNA interference (RNAi), ‘designer drugs’ (eg, Tetrahydrogestrinone) as well as non-approved, emerging or discontinued compounds (eg, aminoimidazolecarboxamideriboside-AICAR, GW1516, selective androgen receptor modulators, hypoxia-inducible factor stabilisers and erythropoietin (Epo)-mimetic agents).

The biggest news to me is dopers are simulating EPO.
The oldest news to me is the peptides and SARM technology. Both are discussed extensively in body building forums.
Rumoured and now confirmed, gene doping technology.

http://bjsm.bmj.com/content/48/10/801.full

Veloclinic is always worth following: http://veloclinic.tumblr.com/

Here's the link to the May, 2014 issue with research authored by the UCI's own Martial Saugy. New readers may not know that Mr. Saugy responded to requests by the UCI to teach riders about the EPO test years ago. Mr. Saugy and the UCI go very, very far back.

http://bjsm.bmj.com/content/48/10.toc

The UCI's Mario Zorzoli also has published something totally discredited by the link above in the same edition. Here's a little refresher on Dr. Zorzoli: http://www.cyclingnews.com/news/zorzoli-back-in-the-uci

 

[DirtyWorks]

2013 EPO Detection Research

2013 research on EPO detection is worrying.

More than 80 different copy epoetins have been compounded. Every novel copy EPO could differ in structure and chemical properties from conventional and biosimilar EPOs such that the direct EPO test may be insensitive to these agents. An alternative test method using SDS-PAGE gel electrophoresis, which differentiates EPO molecules based on the molecular masses, enables the identification of some of the copy epoetins, but it is unlikely that all of these copies can be identified with conventional detection methods.

Excellent detail on how gene doping induces EPO production too. Again, I don't pretend to understand it all.

Also describes cobalt salt tablets increasing EPO production. Yeah, don't do it. Regular use leads to likely organ damage and heart failure.

http://asheducationbook.hematologylibrary.org/content/2013/1/627.full

 

[the sceptic]

2013 research on EPO detection is worrying.

More than 80 different copy epoetins have been compounded. Every novel copy EPO could differ in structure and chemical properties from conventional and biosimilar EPOs such that the direct EPO test may be insensitive to these agents. An alternative test method using SDS-PAGE gel electrophoresis, which differentiates EPO molecules based on the molecular masses, enables the identification of some of the copy epoetins, but it is unlikely that all of these copies can be identified with conventional detection methods.

Excellent detail on how gene doping induces EPO production too. Again, I don't pretend to understand it all.

Also describes cobalt salt tablets increasing EPO production. Yeah, don't do it. Regular use leads to likely organ damage and heart failure.

http://asheducationbook.hematologylibrary.org/content/2013/1/627.full

Good read, thanks.

Correct me if im wrong here, but why would anyone be using "normal" EPO if there are over 80 copies available that does the same thing but may not be detectable? If you dont have to worry about testing positive, you can pretty much do whatever you want. (as long as you know how to manipulate the passport and/or can get the UCI to look the other way).

 

[DirtyWorks]

Good read, thanks.

Correct me if im wrong here, but why would anyone be using "normal" EPO if there are over 80 copies available that does the same thing but may not be detectable? If you dont have to worry about testing positive, you can pretty much do whatever you want. (as long as you know how to manipulate the passport and/or can get the UCI to look the other way).

Let's imagine for a minute that the UCI cares about the 50% Hct rule and would actually sanction someone for it. We know they run soft sanctions by sending out warning letters. Let's say you have JTL's luck, the 50% Hct is the limit.

And, BTW, it seems like you can do detectable EPO anyway. Just do a Hincapie and flee when the testers show up in the "glowing" window. What's out is doing the long-acting EPO CERA.

What's interesting is the 2014 Giro is not showing evidence of EPO performances. Maybe cycling is kind of stuck in low-tech doping?

It's all very interesting.

 

[meat puppet]

Might be interesting: http://www.essex.ac.uk/news/event.aspx?e_id=6578

"It means we could overcome some of the inherent problems with transfusions..."

 

[blackcat]

Good read, thanks.

Correct me if im wrong here, but why would anyone be using "normal" EPO if there are over 80 copies available that does the same thing but may not be detectable? If you dont have to worry about testing positive, you can pretty much do whatever you want. (as long as you know how to manipulate the passport and/or can get the UCI to look the other way).

well, for starters, you need to get your hands on one of those 80, and then, you need to have confidence in what you are buying. if you are buying Eli Lily, or Amgen, atleast you can trust what you are getting is legit, ofcourse, the package could be a chinese counterfeit package of sugar tabs in the foil packaging

 

[blackcat]

Might be interesting: http://www.essex.ac.uk/news/event.aspx?e_id=6578

"It means we could overcome some of the inherent problems with transfusions..."

i heard team GB the track side, were doing gene doping close to a decade back.

 

[the sceptic]

well, for starters, you need to get your hands on one of those 80, and then, you need to have confidence in what you are buying. if you are buying Eli Lily, or Amgen, atleast you can trust what you are getting is legit, ofcourse, the package could be a chinese counterfeit package of sugar tabs in the foil packaging

yeah if youre a low level rider buying the stuff on the internet thats obviously a risk.. But I would guess that the big players are a bit more advanced than that.

Can someone explain how the gene manipulation works?

 

[blackcat]

yeah if youre a low level rider buying the stuff on the internet thats obviously a risk.. But I would guess that the big players are a bit more advanced than that.

Can someone explain how the gene manipulation works?

i think that where the peptides and amino acids are at, you take something, and it manipulates your pituitary gland, to release your own, the endogenous testo/hgh.

by manipulates, i mean, it sends the pituitary the signals to produce your own. i have no understanding about the biochemical structure of this tho

 

[mikeoneill]

surely the biological passport picks up on any new epo variant in high doses

the readings will still be off won't they, no matter what the variant if the dose is high enough?

 

[Will Carter]

i heard team GB the track side, were doing gene doping close to a decade back.

I'd be interested in reading that - can you provide a link?

 

[DirtyWorks]

surely the biological passport picks up on any new epo variant in high doses

Read the link. The researcher isn't prepared to say that. Also, tests for certain kinds of artifacts are difficult enough to develop. Now you want the test to work on all variations. Furthermore, developing an effective test for drugs you will never get the manufacturer to assist you with is exceedingly difficult.

the readings will still be off won't they, no matter what the variant if the dose is high enough?

Chris Horner showed us all how scores don't matter. For others, they get sanctioned. For others still, their case drags on. JTL says hello while he waits.

Again, as frustrating as this research suggests, the 2014 Giro was apparently not done at EPO-induced speeds.

 

[DirtyWorks]

yeah if youre a low level rider buying the stuff on the internet thats obviously a risk.. But I would guess that the big players are a bit more advanced than that.

Can someone explain how the gene manipulation works?

In addition, different pharmacological and genetic approaches may be able to simulate the effects of hypoxia at the cellular level to increase expression of hypoxia-inducible genes such as hypoxia-inducible factor (HIF). HIF will eventually lead to an increase in the production of EPO and, subsequently, HB or RBC mass. Modulation of the hypoxia-induced genes could be achieved by inhibiting HIF-prolyl hydroxylase, a key regulatory enzyme of HIF. Administering drugs that inhibit HIF-prolyl hydroxylase enzymes changes the stability of the HIF-alfa subunit and thus the activation and expression of hypoxia-responsiveness genes.27 Selective activation of the erythropoietic cascade has the potential to induce the full complement of factors necessary for erythropoiesis including EPO, EPO-R, and iron-regulatory genes. Of particular concern are the small molecules such as clinically used iron chelators and small molecules currently in phase 2 or 3 studies. Currently, tests do not exist to detect hypoxia-induced gene “doping” with pharmacological and/or genetic strategies. Pharmaceutical companies already offer HIF-prolyl hydroxylase–inhibitory reagents and it is likely that these drugs are already used by athletes.

http://asheducationbook.hematologylibrary.org/content/2013/1/627.full

I'm definitely out of my league, but it seems like they "turn on" the genes that regulate EPO manufacturing. As mentioned earlier, another way is to use peptides to do the "turning on."

 

[Tinman]

they "turn on" the genes that regulate EPO manufacturing. As mentioned earlier, another way is to use peptides to do the "turning on."

In short, with so many new ways to turn on the body's own EPO production, as well as HGH and other Performance Enhancing Hormones ("PEH"), the fight against PED's looks pretty well lost. Keep in mind the sheer number of test developments required, the time and funds it takes to develop them, and more new ways to stimulate PEH's being discovered all the time.

And Bilharzia has shown us the uselessness of the biopassport. On top of that you can be guaranteed any young new talent has always been at the 50% limit right from "arriving" on the scene.

So it's a brave new world of everyone at the winning level doping within the limits allowed. Everyone else who is truly riding clean is somehow "underperforming". And some occasionally taking a punt and going over the limit in the hope (or rather assumption) they don't get caught when it matters.

 

[King Boonen]

I think you're barking up the wrong tree with gene doping guys.

 

[doolols]

I think you're barking up the wrong tree with gene doping guys.

Why? Is it not at least possible?

 

[King Boonen]

Why? Is it not at least possible?

If you mean scientifically, yes. If you mean for doping, at the moment no. Doping comes from research into other areas, there's no money in doping comparatively, it's all in medicine. Gene therapy is not anywhere near being put into use, the idea that British Cycling have been doing it for years is laughable.

I'm talking specifically about gene therapy, not using small molecules or proteins to activate genes.

 

[Dear Wiggo]

If you mean scientifically, yes. If you mean for doping, at the moment no. Doping comes from research into other areas, there's no money in doping comparatively, it's all in medicine. Gene therapy is not anywhere near being put into use, the idea that British Cycling have been doing it for years is laughable.

I'm talking specifically about gene therapy, not using small molecules or proteins to activate genes.

Genetic modification / manipulation at the genetic level, no.
Stimulating endogenous processes, yes.

Yes?

Certainly confused the flying fat rats tail out of me the first time I read it. Good grief. Can you imagine attempting to modify someone's genetic makeup and getting it wrong!? And then they have children. Eesh.

 

[Catwhoorg]

The nearest you can get to gene doping at this time is say, crossing a TDF rider with an Olympic cyclist (Phinney).

Maybe the Kenny/Trott relationship will provide a similar boost for Team GB in the 2040 Olympics.

 

[Dear Wiggo]

The nearest you can get to gene doping at this time is say, crossing a TDF rider with an Olympic cyclist (Phinney).

Maybe the Kenny/Trott relationship will provide a similar boost for Team GB in the 2040 Olympics.

And food. Pretty sure I read what you're eating can impact on the baby you're growing in your tummy.

 

[DirtyWorks]

Gene therapy is not anywhere near being put into use...

I'm talking specifically about gene therapy, not using small molecules or proteins to activate genes.

Can you expand on this? Go ahead and get technical.

 

[King Boonen]

Can you expand on this? Go ahead and get technical.

Gene therapy is hugely expensive to develop. I was wrong, they recently approved the first treatment so it's obviously further along than when I last looked at it but I'm not sure if Glybera has been used. Glybera is expected to cost in the region of $1.6 million per treatment.


Remember, doping products are almost always medicines beforehand (designer steroids being the exception but the chemistry and methods used were developed for medicines so they are still related). This means that any doping product is only going to become available if it is first developed for medicine. There are some obvious targets that will interest dopers, muscle wasting diseases, blood disorders etc. but the cost is going to be massively prohibitive to all but the richest of sports stars, and getting hold of it is going to be very difficult. It's not something that's going to be mass produced any time soon and because of the delivery vectors it will be very tightly controlled.

The next issue is we are talking about replacing mutated genes in a medical sense. These mutations don't exist in healthy athletes, so chances are using similar products to those developed for medicine will have little to no effect. Again, doping is pretty much worthless to the pharmaceutical business. Yes, a pharmacist may be able to make a load of cash selling EPO to cyclists, but for a company to develop gene therapy, specifically for doping is just not going to happen. For this reason I can't see anything useful coming from gene therapy for a long time.

This, coupled with the cost of developing and producing it make me think that gene doping is years and years away, if it happens at all. It's not something British Cycling could develop, or pay to have developed, and keep quite. We're talking about massive scientific achievements, possible Nobel prizes etc. if it's very successful.


As a more general point there are huge risks involved with gene therapy. If it is incorporated into sex cells then it's unknown how it will affect future generations and the gene pool. For this reason germline gene therapy is prohibited in many countries, this slightly stifles the research slowing it down further (but is very sensible). This is what they mean when they talk about "designer babies" etc.

 

[blackcat]

Gene therapy is hugely expensive to develop. I was wrong, they recently approved the first treatment so it's obviously further along than when I last looked at it but I'm not sure if Glybera has been used. Glybera is expected to cost in the region of $1.6 million per treatment.


Remember, doping products are almost always medicines beforehand (designer steroids being the exception but the chemistry and methods used were developed for medicines so they are still related). This means that any doping product is only going to become available if it is first developed for medicine. There are some obvious targets that will interest dopers, muscle wasting diseases, blood disorders etc. but the cost is going to be massively prohibitive to all but the richest of sports stars, and getting hold of it is going to be very difficult. It's not something that's going to be mass produced any time soon and because of the delivery vectors it will be very tightly controlled.

The next issue is we are talking about replacing mutated genes in a medical sense. These mutations don't exist in healthy athletes, so chances are using similar products to those developed for medicine will have little to no effect. Again, doping is pretty much worthless to the pharmaceutical business. Yes, a pharmacist may be able to make a load of cash selling EPO to cyclists, but for a company to develop gene therapy, specifically for doping is just not going to happen. For this reason I can't see anything useful coming from gene therapy for a long time.

This, coupled with the cost of developing and producing it make me think that gene doping is years and years away, if it happens at all. It's not something British Cycling could develop, or pay to have developed, and keep quite. We're talking about massive scientific achievements, possible Nobel prizes etc. if it's very successful.


As a more general point there are huge risks involved with gene therapy. If it is incorporated into sex cells then it's unknown how it will affect future generations and the gene pool. For this reason germline gene therapy is prohibited in many countries, this slightly stifles the research slowing it down further (but is very sensible). This is what they mean when they talk about "designer babies" etc.

ok, so what i heard, would just have been the peptide/amino acid pathway to activating those pituitary stimilii for the endogenous testo/gh

thanks for the reply KB

 

[blackcat]

The nearest you can get to gene doping at this time is say, crossing a TDF rider with an Olympic cyclist (Phinney).

Maybe the Kenny/Trott relationship will provide a similar boost for Team GB in the 2040 Olympics.

saw Connie Carpenter, (i think she won the rr at olympics in 84LA) talking to Kathy Watt who won the Oly tt in 88 or 92. @Melbourne World rr in Geelong in 2010

 

[Catwhoorg]

As a more general point there are huge risks involved with gene therapy. If it is incorporated into sex cells then it's unknown how it will affect future generations and the gene pool. For this reason germline gene therapy is prohibited in many countries, this slightly stifles the research slowing it down further (but is very sensible). This is what they mean when they talk about "designer babies" etc.

This specifically is why the '3 person' baby which is really the only cure for mitochondrial disease whilst retaining (most of) the parents genetics is being so closely examined.

(Mother with mitochondrial disease has her egg nucleus moved to a 3rd persons egg. Father the fertilizes via IVF).

Permanently changing the human germ line is not something to be taken lightly.

On that specific matter I say use the donor egg intact. (despite being a scientist I guess I can be a bit of a luddite) Not modifying the germ line is a more important principle than the chance for the parents (mother) to have their genes passed on. Heck adopt if they want.

Viral vector genes inserted (into the lungs for CF is one thing under development) is another matter.