Follistatin Gene Therapy Works? (Gain Muscle Without Training) NEW Myostatin Inhibitors!
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- čas přidán 24. 07. 2024
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TIMESTAMPS:
00:00 - Intro Teaser
00:21 - Follistatin Gene Therapy
02:37 - Two New Myostatin Inhibitor Peptides
04:15 - ACE-031 Overview
05:16 - ACE-031 Human Clinical Trials
09:18 - ACE-031 Animal Models
11:24 - ACE-031 Hypothetical Cycle
13:20 - ACE-083 Overview
15:23 - ACE-083 Human Clinical Trials
19:03 - ACE-083 Animal Models
19:53 - Steve’s Conclusions
25:08 - Closing Thoughts
#VigorousSteve #Follistatin #GeneTherapy - Sport
ACE-083 Project GoFundMe: bit.ly/3dV6cFr
AI Bodybuilder: playgroundai.com/post/gigantic-random-bulky-male-model-7-foot-tall-bulky-oversized-cln0vgue702vqs601a9jq286n
Clinical Trials & Studies Discussed:
Kanno, Y. et al. (2013) Selective androgen receptor modulator, YK11, regulates myogenic differentiation of C2C12 myoblasts by follistatin expression. Biological and Pharmaceutical Bulletin, 36(9):1460-5. doi: 10.1248/bpb.b13-00231
sci-hub.zidianzhan.net/10.1248/bpb.b13-00231
ACE-031 / ACVR2B/Fc:
Acceleron Pharma, Inc. (September, 2008) A Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of ACE-031 (ActRIIB-IgG1) in Healthy Postmenopausal Volunteers. NCT00755638
clinicaltrials.gov/study/NCT00755638
Attie, K.M. et al. (March, 2013) A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers. Muscle & Nerve, 47(3):416-23. doi: 10.1002/mus.23539
sci-hub.zidianzhan.net/10.1002/mus.23539
Acceleron Pharma, Inc. (August, 2008) A Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of ACE-031 in Healthy Postmenopausal Women. NCT00952887
clinicaltrials.gov/study/NCT00952887
Attie, K.M. et al. (April 6, 2011) Increased lean mass and muscle volume in healthy post-menopausal women treated with ACE-031 (soluble activin type IIB receptor), an inhibitor of myostatin and other negative regulators of muscle. Proceedings of the American Academy of Neurology.
Acceleron Pharma, Inc (April, 2010) Study of ACE-031 in Subjects With Duchenne Muscular Dystrophy. NCT01099761
clinicaltrials.gov/study/NCT01099761
Campbell, C. et al. (April, 2017) Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial. Muscle & Nerve, 55(4):458-464. doi: 10.1002/mus.25268
sci-hub.zidianzhan.net/10.1002/mus.25268
Cadena, S.M. et al. (September, 2010) Administration of a soluble activin type IIB receptor promotes skeletal muscle growth independent of fiber type. Journal of Applied Physiology, 109(3):635-42. doi: 10.1152/japplphysiol.00866.2009
sci-hub.zidianzhan.net/10.1152/japplphysiol.00866.2009
Klimek, M.E.B. et al. (January 15, 2015) Acute inhibition of myostatin-family proteins preserves skeletal muscle in mouse models of cancer cachexia. Biochemical and Biophysical Research Communications, 391(3):1548-54. doi: 10.1016/j.bbrc.2009.12.123
sci-hub.zidianzhan.net/10.1016/j.bbrc.2009.12.123
Lee. Y.S. et al. (October 15, 2015) Muscle hypertrophy induced by myostatin inhibition accelerates degeneration in dysferlinopathy. Human Molecular Genetics, 24(20):5711-9. doi: 10.1093/hmg/ddv288
sci-hub.zidianzhan.net/10.1093/hmg/ddv288
Lee. Y.S. et al. (October 24, 2015) Genome-wide expression analysis comparing hypertrophic changes in normal and dysferlinopathy mice. Genome Data, 6:253-7. doi: 10.1016/j.gdata.2015.10.010
sci-hub.zidianzhan.net/10.1016/j.gdata.2015.10.010
Barreto, R. et al. (July 12, 2016) Chemotherapy-related cachexia is associated with mitochondrial depletion and the activation of ERK1/2 and p38 MAPKs. Oncotarget, 7(28):43442-43460. doi: 10.18632/oncotarget.9779
sci-hub.zidianzhan.net/10.18632/oncotarget.9779
Bondulich, M.K. et al. (October 27, 2017) Myostatin inhibition prevents skeletal muscle pathophysiology in Huntington's disease mice. Scientific Reports, 7(1):14275. doi: 10.1038/s41598-017-14290-3.
sci-hub.zidianzhan.net/10.1038/s41598-017-14290-3
Barreto, R. et al. () ACVR2B/Fc counteracts chemotherapy-induced loss of muscle and bone mass. Scientific Reports, 7(1):14470. doi: 10.1038/s41598-017-15040-1
sci-hub.zidianzhan.net/10.1038/s41598-017-15040-1
Hulmi, J.J. et al. (April, 2018) Prevention of chemotherapy-induced cachexia by ACVR2B ligand blocking has different effects on heart and skeletal muscle. Journal of Cachexia, Sarcopenia and Muscle, 9(2):417-432. doi: 10.1002/jcsm.12265
sci-hub.zidianzhan.net/10.1002/jcsm.12265
Magga, J. et al. (March 6, 2019) Systemic Blockade of ACVR2B Ligands Protects Myocardium from Acute Ischemia-Reperfusion Injury. Molecular Therapy Journals, 27(3):600-610. doi: 10.1016/j.ymthe.2019.01.013
sci-hub.zidianzhan.net/10.1016/j.ymthe.2019.01.013
Connell, T.M.O. et al. (August 21, 2019) Treatment with Soluble Activin Receptor Type IIB Alters Metabolic Response in Chemotherapy-Induced Cachexia. Cancers, 11(9):1222. doi: 10.3390/cancers11091222.
sci-hub.zidianzhan.net/10.3390/cancers11091222
Szabó, Z. et al. (August, 2020) Systemic blockade of ACVR2B ligands attenuates muscle wasting in ischemic heart failure without compromising cardiac function. The FASEB Journal, 34(8):9911-9924. doi: 10.1096/fj.201903074RR
sci-hub.zidianzhan.net/10.1096/fj.201903074RR
Huot, J.R. et al. (December 2020) ACVR2B antagonism as a countermeasure to multi-organ perturbations in metastatic colorectal cancer cachexia. Journal of Cachexia, Sarcopenia and Muscle, 11(6):1779-1798. doi: 10.1002/jcsm.12642
sci-hub.zidianzhan.net/10.1002/jcsm.12642
Zhong, X. et al. (August 2022) Sex specificity of pancreatic cancer cachexia phenotypes, mechanisms, and treatment in mice and humans: role of Activin. Journal of Cachexia, Sarcopenia and Muscle, 13(4):2146-2161. doi: 10.1002/jcsm.12998
onlinelibrary.wiley.com/doi/10.1002/jcsm.12998
Li, C. et al. (September 2, 2022) The relationship between myodural bridges, hyperplasia of the suboccipital musculature, and intracranial pressure. PLOS One, e0273193. doi: 10.1371/journal.pone.0273193
journals.plos.org/plosone/article?id=10.1371/journal.pone.0273193
ACE-083 / FST288/Fc:
Acceleron Pharma, Inc. (September, 2014) Phase 1 Study of ACE-083 in Healthy Subjects. NCT02257489
clinicaltrials.gov/study/NCT02257489
Glasser, C.E. at al. (June 2018) Locally acting ACE-083 increases muscle volume in healthy volunteers. Muscle & Nerve, 57(6):921-926. doi: 10.1002/mus.26113
sci-hub.zidianzhan.net/10.1002/mus.26113
Acceleron Pharma, Inc. (May 10, 2019) Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) and Charcot-Marie Tooth (CMT) Disease Types 1 and X (CMT1 and CMTX). NCT03943290
clinicaltrials.gov/study/NCT03943290
Thomas, F.P. et al. (May 11, 2022) Randomized Phase 2 Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease. Neurology, 98(23):e2356-e2367. doi: 10.1212/WNL.0000000000200325
www.neurology.org/doi/10.1212/WNL.0000000000200325
Acceleron Pharma, Inc. (July 31, 2017) Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease. NCT03124459
clinicaltrials.gov/study/NCT03124459
Statland, J.M. et al. (July 2022) Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy. Muscle & Nerve, 66(1):50-62. doi: 10.1002/mus.27558
onlinelibrary.wiley.com/doi/10.1002/mus.27558
Thomas, F.P. et al. (May 29, 2020) Results of a phase 2 double-blind placebo-controlled study of a local muscle therapeutic, ACE-083, in subjects with Charcot-Marie-Tooth (CMT) disease. Presented at the 72nd American Academy of Neurology Annual Meeting (virtual).
www.neurology.org/doi/abs/10.1212/wnl.1514
Castonguay, et al. (March, 2019) Follistatin-288-Fc Fusion Protein Promotes Localized Growth of Skeletal Muscle. Journal of Pharmacology and Experimental Therapeutics, 368(3):435-445. doi: 10.1124/jpet.118.252304
sci-hub.zidianzhan.net/10.1124/jpet.118.252304
Pearsall, R.S. et al. (August 6, 2019) Follistatin-based ligand trap ACE-083 induces localized hypertrophy of skeletal muscle with functional improvement in models of neuromuscular disease. Scientific Reports, 9(1):11392. doi: 10.1038/s41598-019-47818-w
sci-hub.zidianzhan.net/10.1038/s41598-019-47818-w
Haha you bastard I can't remember the last time I got Rick Rolled
Question. Does it permanently change genetics?
Takes it. Turns on. Stop taking it. Never turns off. You become a mass of muscle that can no longer move. You’ve finally beat body dysmorphia
YAY!
Ok I need it steve how do I get it?
No, the muscles need to keep on growing till it goes beyond the observable universe and beyond!
@@kamartajsorta like me ?
@@Joe-ui5viwhere you live?
Thanks for taking the time to cover this
I’m going to wait till the super soldier project starts 😂
My calves have hope 🙏
Coach Steve gives us the key to grow a little more in ‘24. Happy New Year brother ! 😌💙🙏✌️
Thank you Steve I have been so interested in these. You’re the best.
Happy new myman
Steve thank you so much for this video. I've been trying to figure this out myself for so long. Hard to piece everything together. More peptide videos please!
"We just want to pin, win and gain muscle" 😂😂😂😂 put that on a t shirt
thanks Steve, happy new year !
that gofundme got me good, nice one steve!
Cant wait to see the 2034 olympia, nick walker at 500lbs at 2% bodyfat
I’m not sure if he’ll be around by then.
Regardless, I am curious how much muscle a human could carry with zero inhibitions.
Love the citations! Thanks, Steve.
Wait, no links to the studies in the description??
They're in the pinned comment buddy
Thanks for pricing it out and allowing me to come the the conclusion that test is always best once again 😂
Test rules all!
holy shit, im excited!
Thanks god there is Steve that do all the dirty work of researching and testing (when it's tempting/worth)
Very interesting, thanks Steve.
I'm excited 🎉🎉 happy new year
Unrelated question, looking at taking pregnenolone, what dosage do you recommend?
I don't think Brian Johnson is eating enough to get excess gains from it.
He stated that lifts light weights only as well.
I'd love to hear you and Peter Attia have a conversation. You should reach out. I love the episodes Derek and he have done.
Loved this video! Definitely interested to see what comes out in the next 10 years in the way of further literature on these.
I think the first heard about a bodybuilder doing this was in one of Regan's vlogs.
Gold. 💛👑
Instructive, informative and interesting like always, pure Special Hard Double 💪 approved stuff, thanks Steve!
The new CGI thumbnail guy is hard at work it seems!
it would be awesome to have this videos in blog forms
And this is the content why we are here :) quite hopeful results!
Very interesting it is hard to find research on this matter
new banger
“Just because you feel small doesn’t mean you have a muscle wasting condition” 🤣😹☠️💀 lmaoooo
I’m waiting on the productivity summary
What you think about potencial add on to with synergistic activin type II receptor blockers such as Bimagrumab that showed some promising data in humans recently?
Yeah that could work, but I didn't really look into Bimagrumab much. It's on the WADA Prohibited list, so that means it's the good shit XD
New editing? I like this sped up style a lot better
Meth, not even once!
Off topic- Hi steve, i would like to propose Chris Masterjohn as possible next podcast guest, he taught me several things such as snip chips genetic testing (like 23andme) isnt enought that in order to be super comprohensive you need whole genome sequening, next the comprohensive nutritional status testing such as genova diagnostics to catch possible micronutriend deficiencies and mitochondrial testing like mitoswab to determine how well your mitochondria work and witch of the complexes can be insuficient. Also his methyline blue E-book is next level.
Does Chris talk about Performance Enhancing Drugs? At all?
@@VigorousSteve not really, but his knowledge especially in the genetic/micronutrient department, might have i belive huge aplications for bodybuilders/strenght athletes/enterpreneurs seeking optimization.
Thanks
Hay Steve I want to start follistatin gene therapy what’s a good clinic in Virginia or do I need to take a trip somewhere?
Alright.. gonna need some of this stuff. Gimme gains and let me just grind with work without having to lift or eat 🤣
Or eat? So you will photosynthesize energy directly from the sun? You green?
@@krane15 I don’t even need the sun. With these drugs, any matter I come across including the atmosphere will just be nitrogenated and accumulate as muscle tissue.
Hopefully you sensed the sarcasm is both the initial comment and this one. These meds come out and people think they can skip the important stuff and just grow.
@@DrAdamHotchkisshe definitely did not pick up the sarcasm. The downside to not partaking in human to human interaction through text is sarcasm cannot be interpreted lol
I bought like 6 vials of ACE 031 from a friend like 2 years ago. He said it was gonna be a big thing, I never used them but I plan on stacking them with YK11 and Follistatin amongst other things later this year. I will probably either just use a vial every week for 6 weeks or 2 vials every two weeks and see if I’ll actually get anything. Cause it sounds like the dose needs to be aggressive and I don’t have that kinda cash so we can see what I’ll get from a smaller dose. Probably nothing but I might as well use it if I got it🤷🏽♂️
ACE-031 is pointless to take unless you have like 500mg-1g. The studies used a much larger dose than you could ever afford.
It prob broke down
@@SoulDelSol I’ve kept it in the fridge/freezer I’m not sure how good it’ll be but it’s worth a shot 🤷🏽♂️
It’s probably good if it’s a chest freezer or one with no auto defrost function. If it has auto defrost then it’s heat shocking the peptides every time it runs the defrost cycle. But either way it’s probably worth a shot if you have it.
All that at once is a major cancer risk
Started taking this today. Just the peptide not the gene therapy with the vector.
If this line of technology works, then bodybuilders will have to start doing sports because everyone will be yacked out of their minds 😅
I was pretty suppriced it wasent a new follistatin verision but the same peptide thats on the market, just prolonged half life ... wich means that the peptide is acully good enough (according to khan) but the regular one needs multiple injections..
Should be able to buy this in china w high mg and make yourself, just sterilize the powder and inj. I have no issue with 5 x inj per day if its a slin pin. Did khan mention wich of the few offical follistatin peptides he is using?
I wounder what khan got the dosing from, to sell it for 25k and you now said it dident even work that well .. thats ... yeah. He talks like he already know it works and the studies but have his gone thrue low vs medium vs high dosing? And so on, like why settle at the amount he did. At 25k every other year we need more results then just a little better fatloss and easier to build muscles
You said dosing every 3 weeks but dosent khan say the peptide verision of his is super short half life?
Has anybody heard about Dr.Khan's stance on what has follistatin gene therapy did to him in terms of benefits ? I remember him announcing he has done it himself. Anyone knows how's he doing ?
I'll be sure to ask him!
@@VigorousSteve Appreciate it
It'd be awesome to get a hold of some but insane amount of money 💰 😳 lol I'm sure there will be some pro trying this out
I like that it’s specific to contractile tissue. I wonder if these are beneficial or consequential to connective tissues ?
Yes, weakens connective tissue
3 or 4% increase in lean mass on a dexascan could potentially be 0% increase of actual muscle. Pretty sure I can increase 4% lean mass on a dexa just by carb loading. Wouldn't have to increase your internal organ size, that kind of fluctuation could easily be just fluid retention (AKA lean mass). Animal models sound great though!!
Search bimagrumab. They have a clinical trial in T2DM patients. They gained muscle and lost fat with no effect on appetite
You really should ask at the end of the video if any grey market vendors would like to sponsor your experiment it would boom their sales let’s be real 😂
When can I buy them lol
Might be a situation where myoststin inhibition through peptides never become commercially viable and you just have to go straight to gene down regulation which is who knows how far away
not that far away
Follistatin 315 does this already.
They've been available for almost twenty years, I took them pre 2008
Rehan Grimes recieved this in one of his videos i believe, and ofcourse alongside working with Milos his gains have been significant to say the least, but how much is actually from the peptide. Prolly not much
You should talk about yk11 the same the supposedly lowers myostatin
If @VigorousSteve is here, why did you stop testosterone, does it matter since you don't really care about LH/FSH production from the pitutary? or, does testosterone in someway directly stops production in the testes?
With exogenous Testosterone in the picture, fertility parameters take longer to improve and are less favorable compared to without it. We're 40 years old, I need every edge I can get.
Have you considered IVF and freezing embryos for future babies?
Makes sense! Good luck brother 👊@@VigorousSteve
I think people overlook the possible deleterious effects on connective tissue and it's inhibited repair. If you enjoy lifting heavy and pursuing strength then I'd say you'd have to be willing to really lighten your weights if/while you were in theory to take such.
Deleterious, more like DELTeterious, go big or go extinct.
@@JonathanJoestarJuicefest nah, you can extinct yourself by becoming unfunctional. Go ahead and get big and fuck your connective tissue up, you'll go extinct because you can't even function.
Wait til you put a few years on and time catches up, one day you won't have such a stupid tone.
In order to inhibit myostatin you also have to decrease connective tissue healing because they're linked.
Are we clear whether the effect of outright inhibition of growth or damage as opposed to a disproportionate lack of gains leading to them being outpaced and becoming the weak link in the muscle tendon unit? Admittedly I haven’t finished the video but last I checked the conclusion was reached through data indicating higher incidence of injuries and not any specific mechanism of said deleterious effect.
Only if you have very low myostatin if you only take a little follistatin your joints and ligaments will be ok
Will mk677 grow my organs
😂😂😂 where are you getting these ai pictures for your thumbnail 😅
Is there a way to test Myostatin levels?
What about follistatin 344?
The mirror says Im smol So i need it
Steve, think it would be wise to buy some Acceleron stock? Did you?
Will they outperform Bitcoin, Eli Lily or Novo Nordisk? I think not! XD
@@VigorousSteve right, but if they hold the patent for this and it becomes successful after further research (even if it takes years) then the stock could skyrocket don’t you think?
Dont forget its 20k one shot.
Algo!
algoooo!!!!
I worry about these peptides that are new. Don’t want to pull a Boston loydd and fuck my kidneys up.
You fool!! you’ve blown a massive opportunity here. We wanted to hear that we could sit on our asses on the couch, eating ice cream, lots of candy, and just pack on the muscle, by taking a shot or two every day. How dare you destroy our hopes and dreams!!
wassup
❤for🇮🇳 pro👊👊
Pro rape?
My UK steroid supplier already stocks ACE-031. From United Peptides.
Muscle gainz without training would be absolut boring. I hope it makes you respond better to Training also so that the exercise is potenciated than normal
We all already have that. The way you look prior to joining a gym.
Did anyone learn anything here?
I guess yk11 is snake oil then?
A bit too fast. I like original video speed
What's funny about Bryan Johnson taking this gene therapy is that it's exactly the opposite of what someone trying to stay alive forever would do. Like damn bro why do you wanna inhibit the inhibition of growth (muscle mass)? Isn't growth going to further shorten your lifespan?
Sounds like you can build too much muscle and become a statue. Once perfected and safe then I can see it being beneficial
In modern time the (colloquial) use of the phrase 'Gene Therapy' has really strayed well and truly away from the pharmacological intent LOL. This is just but one example.
So still impractical ?
Just mad expensive ;)
A lot of no information here
Im not interested in someone that builds muscle without working out i can see where it would have application in cases of certain illnesses though ..personally i like working for my gains enhanced or otherwise
cbum got this done
Pn me for all peptides 💪🏽
What about follistatin 344?
Do you have a link bro to the website ? Cheers