# Anti Myostatin Drugs - The New Anabolic Steroids



## B-GJOE (May 7, 2009)

Interesting article I found

Memorandum from Dr Henning Wackerhage and Dr Aivaras Ratkevicius, School of Medical Sciences, College of Life Sciences & Medicine, University of Aberdeen

ANTI-MYOSTATIN DRUGS: THE NEW ANABOLIC STEROIDS?

1. Myostatin function

Myostatin is a key regulator of muscle mass: it is a peptide that potently inhibits muscle growth. Experimental myostatin knockout in mice or some natural mutations of the myostatin gene increase muscle mass dramatically in mice, cattle and human beings. The case of a boy with twice the normal muscle mass due to a "natural" myostatin mutation was reported widely.

2. Anti-myostatin drugs

Muscle wasting is a problem in a wide variety of conditions that include normal ageing, HIV/AIDS and some forms of cancer. Anti-myostatin therapy seems suitable for many of these conditions. Myostatin is an "easy" drug target because it can be targeted extracellularly, acts tissue specific and because endogenous inhibitors can be mimicked. It is also a commercially attractive drug target because it is suitable for the prevention of muscle wasting in the whole elderly population. This could be a crucial intervention leading to greater independence in ageing Western societies.

3. Current drug development

Wyeth are currently testing the effectiveness of a monoclonal anti-myostatin antibody (MYO-029) on patients with facioscapulohumeral muscular dystrophy (FSHD), Becker muscular dystrophy (BMD) and limb-girdle muscular dystrophy (LGMD). Results are expected for late 2006. Thus it seems likely that anti-myostatin drugs will become available well before the 2012 London Olympics. Bogus anti-myostatin treatments (Myozap) are commercially available showing the desire of bodybuilders and others to achieve muscle growth by inhibiting myostatin.

4. Likelihood of abuse and dangers

Many doping scandals are linked to bodybuilders or strength/power athletes taking agents that aim to increase muscle mass. Thus muscle growth-promoting myostatin inhibitors are likely to be (ab-) used once they become available. At the same time myostatin inhibitors are probably safer than anabolic steroids because myostatin action is muscle specific whereas anabolic steroid affect many organs other than muscle. Anti-myostatin drugs are likely to be the new anabolic steroids.

5. Challenges for drug testers

Monoclonal antibodies (ie the anti-myostatin treatment currently tested) is a new kind of doping agent. It should be easy to detect these antibodies in blood because they are raised in another species. However we are unsure whether such antibodies or their degradation products can be detected in urine. It is, however, likely that future myostatin treatments will not be limited to monoclonal antibodies. There is a series of papers reporting the existence of endogenously produced myostatin-inhibiting peptides. These are nature's models for anti-myostatin therapy and it seems likely that pharmaceutical companies or others will attempt to copy these. Myostatin-inhibiting compounds might be detected by screening libraries of chemical compounds.

6. Executive summary

Myostatin inhibitors are likely to become available well before the 2012 Olympic Games in London. There is little doubt that they will be abused by bodybuilders and other strength/power athletes. Myostatin inhibitors are likely to be safer than anabolic steroids, growth hormone and clenbuterol which are drugs currently used to attempt to increase muscle mass. If monoclonal anti-myostatin antibodies are used to inhibit myostatin then the detection in blood should be easy but it is unclear whether the detection in urine is feasible. Research is needed to develop urine-based detection methods.

ADDITIONAL INFORMATION

The potential for different HETs, including drugs, genetic modification and technological devices, to be used legally or otherwise for enhancing sporting performance, now and in the future

I wish to comment on the likelihood that new HETs will be developed and used in sport. Currently molecular biologists and sports and exercise scientists discover at new mechanisms and genetic variations that regulate factors such as muscle growth, capillarity, oxygen transport capacity, energy metabolism and heart growth. Mechanistic knowledge allows us to understand how physical training induces adaptations. It is also crucial knowledge for developing treatments (or HETs) that target these mechanisms for therapeutic aims. For example, the discovery of erythropoietin (EPO) laid the foundation for the synthesis of this hormone. Synthetic EPO can be used to increase red blood cell production in patients with low red blood cell count and in endurance athletes where it increases oxygen transport capacity. The discovery of the muscle growth inhibitor myostatin triggered the development of monoclonal antibodies against myostatin. These can potentially be used to increase muscle mass in > 75 year olds or in strength athletes. Novel HETs are likely to be developed especially for mechanisms that can be targeted extracellularly (both EPO and myostatin can be targeted extracellularly). In my opinion serious genetic manipulation of athletes is unlikely to be attempted before 2012 because it is technically difficult and the type of desired and side effects are unclear. To conclude it seems likely that novel HETs will be developed and used by athletes before the London 2012 Olympics.

Steps that could be taken to minimise the use of illegal HETs at the 2012 Olympics

I don't have any new ideas to contribute.

The case, both scientific and ethical, for allowing the use of different HETs in sport and the role of the public, Government and Parliament in influencing the regulatory framework for the use of HETs in sport

Without being a legal expert I feel that there is a case for a strong legal deterrent against using the most dangerous doping agents such as EPO. Seven elite cyclists died of sudden cardiac death between 2003 and 2004 alone (The Observer, Sunday 7 March 2004) and it seems very likely if not obvious that most if not all of these deaths are related to the use of EPO or related agents. Thus, government may wish to consider strengthening the law to try to prevent the use of such agents by athletes.

For all other agents I feel that the anti-doping policies by most sporting associations are adequate. The government and parliament should consider lobbying for removing sports from the Olympic programme that do not sufficiently control doping.

The state of the UK research and skills base underpinning the development of new HETs, and technologies to facilitate their detection

Sports and exercise research is probably less well funded in the UK than in the US or Scandinavia. There are several researchers [Goldspink, Harridge, Montgomery (London), Wagenmakers (Birmingham), Rennie, Greenhaff (Derby/Nottingham). Harris (Chichester), Maughan (Loughborough) and Baar, Sakamoto, Hardie (Dundee)] that make important contributions to the discovery of exercise mechanisms and genetic variations that are related to performance, therapies and HET development. Additional financial support for such research is desirable.

It is unfortunate that the practical skills (ie biochemical, molecular biology and genetic techniques) necessary for mechanistic exercise research are not often taught as part of sports and exercise science degrees. At Aberdeen we have thus decided to develop a MSc in Molecular Exercise Physiology where hands on training in such techniques is a key component. It is desirable that such skills are also developed as part of other sports and exercise science programmes.

The great challenge for HET detection is the detection of HETs or their degradation products in urine unless blood samples are taken. Some new classes of HETs (for example antibodies) require novel approaches for their detection in urine which may be difficult.

May 2006

Source http://www.parliament.the-stationery-office.co.uk/pa/cm200607/cmselect/cmsctech/67/67we07.htm


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## BigBalls (Aug 13, 2010)

crazy maybe these will be produce a new era in bbing


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## RICKYT (Aug 7, 2010)

very interesting iv been following this drug for a while but still nothing on the black market yet but its in the docs drug cabinets now so hopfully not long


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## Jake1436114563 (May 9, 2008)

I remember reading about these drugs a couple of years back. Wonder how far off we are from them being actually made and used.....


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## B-GJOE (May 7, 2009)

RICKYT said:


> very interesting iv been following this drug for a while but still nothing on the black market yet but its in the docs drug cabinets now so hopfully not long


It's going to happen soon, for sure, then BOOM! A new era of bodybuilding will rise.

Maybe it already is...........FOLLISTATIN

http://www.prospecbio.com/Follistatin_Human_3

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

Wiki Says

Clinical significance

Follistatin is being studied for its role in regulation of muscle growth in mice, as an *antagonist to myostatin* (also known as GDF-8, a TGF superfamily member) which inhibits excessive muscle growth. Lee & McPherron demonstrated that inhibition of GDF-8, either by genetic elimination (knockout mice) or by increasing the amount of follistatin, resulted in greatly increased muscle mass. [3][4] In 2009, research with macaque monkeys demonstrated that regulating follistatin via gene therapy also resulted in muscle growth and increases in strength. This research paves the way for human clinical trials, which are hoped to begin in the summer of 2010 on Inclusion body myositis.[5]

A study has also shown that increased levels of follistatin, by leading to increased muscle mass of certain core muscular groups, can increase life expectancy in cases of spinal muscular atrophy (SMA) in animal models. [6]

It is also being investigated for its involvement in polycystic ovary syndrome (PCOS), though there is debate as to its direct role in this infertility disease.


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## pea head (May 28, 2008)

SOUNDS good but im thinking this will end up weaking the bones/joints.


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## Dezw (May 13, 2009)

Yay, more stuff to experiment on myself with.


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## B-GJOE (May 7, 2009)

Fcuking Hell http://www.prospecbio.com/ these guys have got every flipping peptide known to man. For the scientifically inclined biochemists amongst you, you could really go to town with what these guys have to offer.


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## B-GJOE (May 7, 2009)

pea head said:


> SOUNDS good but im thinking this will end up weaking the bones/joints.


25g of Cissus will sort that!

I'm sure the bodybuilding community will come up with some other drug to combat the negative side of any myostatin inhibitor. We're experts in polypharmacy :thumb: :whistling:


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## kingliam84 (Feb 7, 2010)

sounds futristic kinda stuff lol


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## B-GJOE (May 7, 2009)

Just done a search for *Recombinant Proteins* on Google, and it is scary what is available out there. For example, 1 site in the top 10 google

5,000 Purified Human Proteins from HEK293 Cells

For those that don't know what the Hell I am going on about, recombinant proteins is basically genetically modifying bacteria to produce synthetic clones of human peptides. This is where your HGH, IGF's, GHRP's all come from.


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## B-GJOE (May 7, 2009)

BUMP


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## LittleChris (Jan 17, 2009)

B|GJOE said:


> BUMP


x2 :thumbup1:


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## B-GJOE (May 7, 2009)

LittleChris said:


> x2 :thumbup1:


I keep trying to get this Myostatin thing going, but the threads seem to fall off a cliff by about end page 2. Surely someone out there is really looking into the subject on our behalf, and with all them peptides available, surely something will block it, or occupy receptors or something.......


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## brockles (Jun 23, 2009)

Havent read it but its just a myostatin inhibitor? Been info on them knokcing around a few years. Ever see that baby who was like 1 or 2 and could do the iron cross between his mums hands?Ever seen a Belgian Blue? Welcome to a lack of myostatin!


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## SK-XO (Aug 6, 2009)

Good article Joe, reps to you.

Do a lot of the pro's not have myostatin disorders? alough amazing genetics I had read that some of them have myostatin defficiency etc.


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## LittleChris (Jan 17, 2009)

Rumours Flex was deficient in it, although I doubt he underwent tests.


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## brockles (Jun 23, 2009)

I imagine anyone who has myostatin deficiency disorders wont ever need to take steroids!


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## Joshua (Aug 21, 2008)

B|GJOE said:


> Just done a search for *Recombinant Proteins* on Google, and it is scary what is available out there. For example, 1 site in the top 10 google
> 
> 5,000 Purified Human Proteins from HEK293 Cells
> 
> For those that don't know what the Hell I am going on about, recombinant proteins is basically genetically modifying bacteria to produce synthetic clones of human peptides. This is where your HGH, IGF's, GHRP's all come from.


Why would HEK293 cell proteins be of use to you?

There are loads of proteins which will do all sort of things in the body - many of which are extremely undesirable. One of my concerns with the increase in peptide use in bodybuilding is that one can do all sorts of things with peptides and a small mistake in the name can yield massive changes in effect.



B|GJOE said:


> It's going to happen soon, for sure, then BOOM! A new era of bodybuilding will rise.
> 
> Maybe it already is...........FOLLISTATIN
> 
> ...


Follistatin is not a good PED IMHO - it is far too promiscuous in its effects, and can cause all sorts of other growth other than muscle, such as widescale organ growth.

J


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## B-GJOE (May 7, 2009)

Joshua said:


> Why would HEK293 cell proteins be of use to you?
> 
> There are loads of proteins which will do all sort of things in the body - many of which are extremely undesirable. One of my concerns with the increase in peptide use in bodybuilding is that one can do all sorts of things with peptides and a small mistake in the name can yield massive changes in effect.
> 
> ...


I haven't read too much into it, but are peptides not synthesised from E-Coli bacteria via genetic mutation.


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## Joshua (Aug 21, 2008)

Yep. I have no problem with the way they are made. I would far prefer to take a recombinant form than one extracted from glandulars.

The point I was getting at was there are enormous numbers of different peptides. In addition to the natural ones occurring in organisms, there are synthetic ones where bits are added or chopped off the sequence of aminos. The end result being loads of different peptides, which can change the way an organism works.

Some peptides will have highly specific effects eg( myostatin ) which affects skeletal muscle, and others will have very wide ranging effects eg ( follistatin ). The reason why follistatin will increase skeletal muscle is that it interacts with a system called activin-inhibit-follistatin axis [ checkout this for an intro ]. This axis is a major regulator of growth and development in many organisms.

Another interesting peptide is aMSH / melanotan 2 - although it has the obvious effects on skin pigmentation it also has psychoactive effects on hunger/satiety and on sex drive. This indicates that it is affecting several pretty core signalling systems in the body.

Part of my concern with uninformed use of peptides, is that with AAS people are generally limited to a few actives, and even then some people mess up on what they take eg( getting mixed up between oxandrolone and oxymethalone ). Tis far too easy for people to take myostatin antibodies, simply by seeing the words myostatin and anti, and get a nasty reaction (This mistake was actually made). I have also heard chaps talking of taking various growth factors, on the basis that they contain the word "growth" and assume that it will make them huge. Some of these are very powerful agents which are used in tumour promotion in animal models in the lab, others can cause cytokine storms or severe immune responses - checkout [ here ] a drug trial in 2006 that was in many of the UK papers where a anti-CD28 antibody was trialled which caused multiple organ failure in the subjects, even though it had been used well in animal models.

J


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## thereisnoexit (Aug 26, 2009)

I've actually posted about this before - the trick is to find a combination of protiens which will join with myostatin (and mystatin only) redering it useless like the hemogloblins igf-1 combines with or alternatively find a protien which will bind to the same receptor but not activate it as nolva does with breast tissue.

The issue is that that unique combination may not exist - and i dont believe for a second it has been achieved yet.


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## thereisnoexit (Aug 26, 2009)

That site has to be BS... you can buy HIV?!


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## thereisnoexit (Aug 26, 2009)

LittleChris said:


> Rumours Flex was deficient in it, although I doubt he underwent tests.


He was meant to not have the receptor... which is essentially the same thing - I personally dont buy it


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## lolik (Apr 24, 2010)

very interesting guess we have to wait and see


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## green19210 (Jul 26, 2010)

this sounds extremley intressting as i have to do my dissertation purposal this year and plan to do it on steriods...this is another avenue that i could do extensive research on!


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## spudsy (May 13, 2009)

I seem to remember reading an article about kai Green using myostatin manipulation... his physique has certainly got a unique look and i think his "look" is gonna be the way bb'ing goes over the next few years.

He looks almost alien(in a good way lol) compared to the physiques of 30 odd years ago.... the mind boggles as to where we'll be at in another 30!


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## B-GJOE (May 7, 2009)

spudsy said:


> I seem to remember reading an article about kai Green using myostatin manipulation... his physique has certainly got a unique look and i think his "look" is gonna be the way bb'ing goes over the next few years.
> 
> He looks almost alien(in a good way lol) compared to the physiques of 30 odd years ago.... the mind boggles as to where we'll be at in another 30!


He probably has been. There were drug trials on a substance called

MYO-029 (Stamulumab)

But research ceased in March 2008, the drug company developing it stopped.

On MYO-029



> However, the investigators found no improvements in muscle strength or function, and no statistically significant muscle growth in trial participants. (The authors note that the study was not designed to measure efficacy.)


Source http://www.mda.org/research/080311md_myo-029.html

However, this didn't stop some people trying to scam something out of it.

http://www.xtremebodybuilding.net/sten-labs/7395-pre-order-myo-029-a.html

http://www.anabolic-enhancement.com/forum/showthread.php?t=21126

Other usefull Links on MYO-029

http://onlinelibrary.wiley.com/doi/10.1002/ana.21338/full

http://www.physorg.com/news124465547.html

Then there is the natural Myostatin Inhibitors (Yeah! RIGHT!)

MYO-T12

Apparently derived from fertilised chicken eggs.

The hype seems pretty good, but leaves me with a large element of doubt!


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## Joshua (Aug 21, 2008)

Joe - IIRC those modified chick egg idea was based on delivering follistatin orally. If this is the case, regardless of the dose necessary, whether it is active follistatin, or whether it can even get through the gut to the target site, there is the matter of whether one would want follistatin working its magic in one's gastrointestinal tract or acting systemically. It could lead to users having large amounts of offal instead of skeletal muscle. IMHO, it will do little [hunch]. Either way, I think your doubt is well justified.

J


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## huarache (May 28, 2012)

ive seen this, been looking at it for ages, i dont understand all these different peps but i remember looking at that whippet that was born with a myostatin deficiency, although because of the insane muscle mass it developed naturally, because of the 'disease' its organs remain the same size and it ended up dying like half the age didnt it...

would love to see a human with it


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## musio (Jan 25, 2008)




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