Follistatin, ACTN3, IGF-1, shRNA myostain and gene therapy

[radone]

There is good scientific evidence for the use of gene therapy for follistatin and IGF-1. There is also good potential with ACTN3 (sprinter's gene) and shRNA for myostatin (myostatin inhibitor). (I am a real researcher, studying athletic performance enhancement and the treatment of muscle diseases) I am currently working on a research project related to these and some other genes. If you compare gene therapy versus injection of the gene product (peptide or protein), there are definite safety advantages to administration of the peptide. Has anyone else observed this same research? My question is related to gene therapy with IGF-1. In theory, you should be able to obtain similar results from the injection of IGF-1 peptide as you would with IGF-1 AAV gene therapy. Of course, the peptide will require frequent dosing. It has been my experience that the IGF-1 peptide does not even come close to achieving the results that gene therapy does. Any thoughts?

 

[bigironkiller]

What degrees do you have? Always wanted to be a researcher.

 

[radone]

Undergraduate was biochemistry. I have an MD, but also post graduate work in Molecular Biology and Biochem. My research has been mainly for cancer gene therapy, but got into anabolic work for cancer muscle wasting. Once I started working on muscle building, I have become completely consumed. The potential is very exciting.

 

[JohnnieFreeze]

Ive read some studies about gene therapy for muscle growth..subjects were able to gain a higher degree of muscle, and in a matter of weeks rather than months like with simple injections..
but unless you're Bill Gates its probably not a realistic option for most.

 

[radone]

I agree that it isn't cheap. However, a single injection can give 2 plus years of muscle 2-4x greater than steroids. If you compare it, in the long run, gene therapy is a better value.

 

[radone]

My initial post was really meant to see if anyone is getting good results injecting IGF-1. The gene therapy for IGF-1 in animals was very impressive. It seems that you should be able to obtain similar results with peptide injections. Plus with peptide injections, you control the amount. However, I suspect the results of peptide injections fall well short of gene therapy. The reason I ask, is related to follistatin and actn-3. The follistatin peptide is available, but too expensive. I think it could be produced in bulk, which would make it more reasonable in price. I have not found actn-3 available as a peptide. It too could be created by a custom peptide production. However, if the peptide injections do not work that well, then it would be a wasted effort. It would be better to pursue the gene therapy avenue. Thanks for any help!

 

[darkvard]

is it even safe to perform gene therapy on humans?

 

[lyfespan]

interested in reading a lil more about this. Been intrigued by the myostatin inhibition, since seeing thats world's strongest toddler on TLC.

as well as whating to know more about igf-1, after all im 35

 

[radone]

Darkvard,

There are several types of gene therapy vectors. Adenoviruses are fairly safe. There is a gene therapy for treating cancer (gendacine) approved in China using adenoviruses. Adeno associated virus (AAV) are probably the one of choice. There is a low immune response with good gene expression. Retroviral vectors (ie Lentivirus) are effective, but much more dangerous. In human trials, this type has caused cancer.
Overall, it is not fully known if gene therapy is safe. Adeno and AAV seem to be, but experience is limited. There are some human trials for treating muscle dystropies beginning soon.

 

[darkvard]

Darkvard,

There are several types of gene therapy vectors. Adenoviruses are fairly safe. There is a gene therapy for treating cancer (gendacine) approved in China using adenoviruses. Adeno associated virus (AAV) are probably the one of choice. There is a low immune response with good gene expression. Retroviral vectors (ie Lentivirus) are effective, but much more dangerous. In human trials, this type has caused cancer.
Overall, it is not fully known if gene therapy is safe. Adeno and AAV seem to be, but experience is limited. There are some human trials for treating muscle dystropies beginning soon.

But nobody is doing it for bodybuilding yet? right

 

[bigironkiller]

Radone,

Any advances you have heard of regaurding spinal disc herniation? I know there are trials with fibrin/collagen injections. Also I believe in Europe they withdraw a portion of the injured disc, basically regrow the material in a lab and reinhect it back into the disc. What are your thoughts?

 

[radone]

Bigironkiller,

I am glad you asked. That is my speciality. I do minimally invasive imaged guided spine procedures.
You should research ozone disc therapy. It is used more in Europe, though you can find it in the US. It has good success, better than surgery for an isolated disc herniation. There are a few other options for disc herniations. There are mechanical discectomy (looks like a corkscrew) which pulls out a small amount of disc (Stryker Decompressor is the device name). There is also laser discectomy. This burns a small amount of disc in the center, which can cause the disc to retract, treating the herniation.

For these mentioned therapies to work, the disc herniation needs to be contained. So, if you have an annular tear with disc extrusion, these are not a good options.

Overall, Ozone disc injection/therapy seems to have the best results.

I hope this info helps!

Radone

 

[radone]

Darkvard,

I don't think they are. But I am sure that once there is a little more data or when the agents are more available, then it will be used for performance enhancement. The researchers are predicting that it will be showing up in athletes within the next 2 years. There is no way to test for it, except by muscle biopsy. WADA has put a lot of effort in to developing a test, with no real luck.
Follisatin significantly increases fast twitch type II muscle fibers. I heard a researcher estimate from the animal data that a human treated may be able to run up to 46 mph with an estimated 40 yard dash speed of 2.5 seconds. Now, I think that is unlikely, but sub 4 second speed is a definite possibility. Can you image a NFL running back with that type of speed?

This area of research is fascinating!

 

[JohnnieFreeze]

I agree that it isn't cheap. However, a single injection can give 2 plus years of muscle 2-4x greater than steroids. If you compare it, in the long run, gene therapy is a better value.

I agree...plus its muscle that wont disappear when the injections stop..you just need lots of dough upfront for this kind of thing. I did hear a story of a guy supposedly doing some form of myo-blocking drug..and running him thousands for a 4-6 week cycle.

 

[darkvard]

wasn't a big side effect of myostatin inhibition that joints would become weak and frail?

 

[sanchezgreg18]

radone: have you heard of MYO-029? supposedly a myostatin inhibiting peptide?


supposedly the peptide:

"appears to block the actions of a protein- GDF8- that decreases muscle mass, increases fat accumilation, and increases blood glucose. As an anti-GDF8 antibody, MYO-029 has the potential to decrease the high glucose levels that characterize Type 2 diabetes. MYO-029 also may have the potential to treat muscle-waisting diseases such as age related frailty and muscular dystrophy."

 

[radone]

I have heard about myo-029. It is a monoclonal antibody blocking the myostatin receptor. That helps block the effect of myostatin. The trials weren't super exciting. The company that was developing it has decided not to move any further with it. This doesn't mean that it would not work for general muscle enhancement, but just not great for muscular dystophies. The problem is the fact that it is monclonal antibody. Those type of drugs generally have bad side effects or allergy problems. There is another drug acvr2b, which is soluble (free) mysotatin receptor. The thought is that it will bind myostatin and inhibit it from stimulating the real receptor. The study results that i read were pretty good. I think it may be available as research products, but pricing is too high. The dose in mice was 10-50 mg/kg.
Overall, Follistatin is still the most promising option.

In regard to tendon tear/rupture. There is some concern with myostatin inhibitors. This is mostly due to the fact that the muscle becomes stronger than the tendon is designed to handle. I have not heard this being as much of a problem with follistatin, but it is still a mild concern.

 

[JohnnieFreeze]

I have heard about myo-029. It is a monoclonal antibody blocking the myostatin receptor. That helps block the effect of myostatin. The trials weren't super exciting. The company that was developing it has decided not to move any further with it. This doesn't mean that it would not work for general muscle enhancement, but just not great for muscular dystophies. The problem is the fact that it is monclonal antibody. Those type of drugs generally have bad side effects or allergy problems. There is another drug acvr2b, which is soluble (free) mysotatin receptor. The thought is that it will bind myostatin and inhibit it from stimulating the real receptor. The study results that i read were pretty good. I think it may be available as research products, but pricing is too high. The dose in mice was 10-50 mg/kg.
Overall, Follistatin is still the most promising option.

In regard to tendon tear/rupture. There is some concern with myostatin inhibitors. This is mostly due to the fact that the muscle becomes stronger than the tendon is designed to handle. I have not heard this being as much of a problem with follistatin, but it is still a mild concern.

Pretty much explains why the price for myo-029 has gone down..lol

 

[radone]

JohnnieFreeze,

You are probably right. Researchers are losing interest for that one. I have checked around on research grade acvr2b. It seems like a better choice. It is just too high for a researcher in today's economy. I will keep an eye out for a better deal.

 

[ezza]

This sounds incredibly interesting. I wonder how many people out there have tried this on themselves. I did a quick search and it is readily available only thing is for close to 5G you only get 1 mg. Very expensive if doses need to be between 10-50mg/kg.

 

[JohnnieFreeze]

JohnnieFreeze,

You are probably right. Researchers are losing interest for that one. I have checked around on research grade acvr2b. It seems like a better choice. It is just too high for a researcher in today's economy. I will keep an eye out for a better deal.

great..please do keep in touch if you come across a "deal". :fingersx:

 

[radone]

It is very expensive. There may be some options for custom bulk synthesis. That may get the prices down to a reasonable level. Also, I forgot to mention that was once a week dosing at 10-50mg/kg. I did see some research that suggest that dosing might be effective for every 3-4 weeks. That would really cut the amount needed along with the associated cost.

Radone

 

[angelo212]

Hey Radone,
myo-029 is available at some research chem sites now. You think it's a waste of money?

 

[xxl610]

super interesting info radone.

 

[xxl610]

do you know of any good sites that follow the research on these experimental gene therapys. like the one being tested china that you mentioned.

 

[radone]

Angelo,

I don't think I would try it. That type of drug tends to have a lot of sides. Now acvr2b, that would be worth trying.

 

[radone]

xxl610,

There is some info on genetherapy dot net. If you google follistatin or myostatin inhibitors there is also some good info.

 

[radone]

xxl610,

There is some info on genetherapy dot net. If you google follistatin or myostatin inhibitors there is also some good info.

 

[superchip]

There is good scientific evidence for the use of gene therapy for follistatin and IGF-1. There is also good potential with ACTN3 (sprinter's gene) and shRNA for myostatin (myostatin inhibitor). (I am a real researcher, studying athletic performance enhancement and the treatment of muscle diseases) I am currently working on a research project related to these and some other genes. If you compare gene therapy versus injection of the gene product (peptide or protein), there are definite safety advantages to administration of the peptide. Has anyone else observed this same research? My question is related to gene therapy with IGF-1. In theory, you should be able to obtain similar results from the injection of IGF-1 peptide as you would with IGF-1 AAV gene therapy. Of course, the peptide will require frequent dosing. It has been my experience that the IGF-1 peptide does not even come close to achieving the results that gene therapy does. Any thoughts?

so what you mean is that the gene therapy with igf-1 has the same effect as if you would inject igf-1 ed and have better results.?? so basicly what it does is raising your igf-1 level in the body to a higher level , even higher than if you would just inject a fair amount..?? or am i misunderstanding something here?

in my opinion having continiously high igf-1 levels in the body is not something you want to do to yourself sindse it will probably only give you cancer quick..

myostatin blockage is interesting though.. if you can get past the tendon problem.. and have some more data on human tests.. and cut the treatment price down to 1/10th of what it is now.. and ...

 

[radone]

Superchip,
Take a look at IGF gene therapy studies done by Dr. Lee Sweeney. The idea is that direct intramuscular injection would lead to increased IGF only in the muscle. So, the other risk associated with IGF should be reduced. These are only animal studies, so who knows how the results will be in humans. I agree you would have to be concerned about adverse effects. But just look at those mice that were treated. I don't think people injecting the IGF peptide are getting the same results. Why does the gene therapy bulk up a mouse, but injecting the peptide doesn't seem to be even close.

As for myostatin inhibitors and the tendon problem, there is a fix for that. Take a look at BMP14 and BMP12 (bone morphogenic protein) injections for tendons. They have a gene therapy for that too!

 

[hman85]

Super interesting! Good convo guys

 

[gobig1]

I can't believe such an interesting topic has just died off for almost a year now... I'm sitting over here in the big sand box wondering what the latest developments are with Follistatin, et. all, and other new developments in the niche world of gene-therapies...

Anyone got the latest scoop...

 

[jayice]

I can't believe such an interesting topic has just died off for almost a year now... I'm sitting over here in the big sand box wondering what the latest developments are with Follistatin, et. all, and other new developments in the niche world of gene-therapies...

Anyone got the latest scoop...

EXACTLY! i just stumbled up here now! and with the developments with Follistatin, ACTN3 and ACE-031 we could really use Radone's opinion!

 

[jayice]

bump for interest

 

[grega60438]

I have seen positive Follistatin logs, but I suspect some of those have a sales agenda. IMO it seems many of the average Joe logs have not been impressed with Follistatin, and some got sick from it. Some suspect the Follistatin quality was not up to par. I really want to like Follistatin, but these quality issues are concerning. I imagine there are many who feel the same concerns. It is a shame as it seems these quality issues may be hindering some potential Follistatin research. I hope this improves soon, so that we can better realize the potential of Follistatin.

 

[Spaniard]

Still no updates? You would think after a few years there would be some sort of research data appearing???

 

[IBE]

all follistatin on the black market are fake and we have some being tested from two different labs and will report next week when they are finished. I have been trying to tell everyone this for a while but now going to prove it

 

[Spaniard]

You have actual follistatin coming out? Please keep me updated.

 

[Jorsn]

all follistatin on the black market are fake and we have some being tested from two different labs and will report next week when they are finished. I have been trying to tell everyone this for a while but now going to prove it

Finally someone who has seen the light!

 

[Jorsn]

You have actual follistatin coming out? Please keep me updated.

That's not what he said. He said he was going to test the bunk Follistatin.

 

[kvothe]

interested in the results, subbed

 

[Whacked]

Wont this stuff allow ALL MUSCLE to grow (heart, along with other muscles we do not necessarily want to grow)

If so, scary stuff.

 

[Spaniard]

Got a little over zealous.

 

[Spaniard]

Wont this stuff allow ALL MUSCLE to grow (heart, along with other muscles we do not necessarily want to grow)

If so, scary stuff.

No I believe the preliminary reports have said it doesn't have any adverse effect on cardiac muscle. It only effects skeletal muscle.

 

[Whacked]

Very cool