maxmuscle1
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LATEST IN FUTURE DRUG DISCOVERY !!
“TRUE” MYOSTATIN INHIBITORS
**[GDF-8 basic definition is : Myostatin ] BTW
Taldefgrobep alfa (also known as BHV2000) is a modified adnectin designed to specifically bind to myostatin (GDF-8). Taldefgrobep is a fully human anti-myostatin recombinant protein that lowers free myostatin and acts as an Activin 2b receptor antagonist with the myostatin-taldefgrobep complex.
True Myostatin Inhibitor Fast Tracked !!
(Biohaven Pharma company developed it but, it is owned by Roche)
Finally Phase 3 development to increase muscle mass(mainly for the spine at this time)! Fast track designation from the U.S. FDA for taldefgrobep alfa, a novel anti-myostatin adnectin,Taldefgrobep alfa (also known as BHV2000) is a modified adnectin designed to specifically bind to myostatin (GDF-8).
How exactly does it work? It is dual-acting,
It binds to myostatin to both lower overall myostatin levels and also function as a receptor antagonist, thereby blocking myostatin signaling in skeletal muscles.
Taldefgrobep is a fully human anti-myostatin recombinant protein that lowers free myostatin and acts as an Activin 2b receptor antagonist with the myostatin-taldefgrobep complex. Adnectins are an established proprietary protein therapeutic class based on human fibronectin, an extracellular protein that is naturally abundant in human serum. They are approving it is for : “Spinal Muscular Dystrophy” as it increases spinal muscle mass and is “Anabolic”. They are giving the sick DMD patients intrathecal Injections into the spine. I imagine someone will use IM or other. “
Both (acceleron’s inhibitor drugs)ACE-031 and ACE-083 are capable of binding members of the TGF-β superfamily, including not only MSTN and GDF-11 but also activins. A third biologic in this group is *Bimagrumab (Novartis) a monoclonal antibody blocks signaling by multiple ligands utilizing both ACVR2 and ACVR2B. Max - “Even though they do not approve these myostatin drugs, sarm, AR ligand activators often (or at all), it is because they cannot openly produce a drug with “Anabolic” effects unless it is to treat a disease like Duchenne’s/MD , MS, Cancer, AIDS, Fibromyalgia and other muscle wasting diseases ending in -“atrophy”. So just because the FDA doesn’t approve it, or it fails at trials ; you have to look at the definition of why it failed.
In my experience, almost any “anabolic” compound is unapproved due to the pressure from not only the FDA/DEA/FTC but, WADA and the IOC seem to have more influence than the other 3 combined. In fact they form drug testing by urine, blood, hair before any ped ergogenic, anabolic, or stimulant is even close to hitting stage 2 trials.
Eli Lilly’s Landogrozumab (LY2495655) experimental pharmaceutical drug designed for the treatment of muscle wasting disorders. The drug did increase lean muscle mass, accompanied by a persistent decrease in fat mass by inhibiting GDF-8(Myostatin).
Term definitions:
“Myopenia” muscle loss/wasting disorders
“Sarcopenia” - age related muscle loss
“Cachexia” is muscle wasting due to cancer, AIDS/HIV, Anorexia .
History of AAS, PED’s; Newer term : APED (Appearance of performance enhancing drug) LMAO
, just the appearance! :
Due to the “1990 The Anabolic Steroids Act”, which passed as part of the Crime Control Act of 1990, which placed anabolic steroids into Schedule III. In 2003, the Controlled Substance Act was amended to include prohormones (steroid precursors) since they may potentially act as steroid hormones. The Anabolic Steroid Control Act of 2004 was introduced, which took effect in January 2005. The Designer Anabolic Steroid Control Act of 2014 even added plant herbs, botanicals, or concentrate, metabolite, or extract thereof.
The lack of research studies & trials using AAS has disrupted scientific research on animals & humans. These archaic and erroneous laws based on “False & outright Fake Studies, published artices, and scare tactics have truly set us behind of what could unlock healthful therapeutic AAS/PED’s from the past using new drug forms, nano-crystallization, chemical and pharmaceutical delivery systems. Hopefully in the next decade; scheduling will change here and abroad.
Biologicals Drugs :
*Novartis’s bimagrumab was tested in 2 trials for sarcopenia in older adults and resulted in significant increases in mean lean body mass of 6%–8%.
*Regeneron’s REGN1033 for age-related sarcopenia have not yet been published, the data that have been reported show major improvements in lean muscle mass and a decrease in fat mass, post operatively- total hip arthroplasty. The patients were followed for 6 months post rehabilitation, the patients that received the stage 2 trial drug gained more than double the lean muscle than patients that received Novartis’s Bimagrumab .
Novartis’s/Versanis is in stage 2 trials of Bimagrumab in combination with semaglutide for the treatment of obesity has begun enrolling at sites in the U.S., Australia, and New Zealand.
Myl1 promoter/enhancer drug was shown to cause a hypermuscling phenotype characterized by increased fiber numbers and increased fiber sizes
A monoclonal antibody directed against the activin type 2 receptors is capable of inducing muscle fiber hypertrophy when administered systemically to adult mice. At high doses, in fact, just two injections of the ACVR2B/Fc decoy receptor can induce over 50% muscle growth over a span of two weeks , modified activin A propeptide, which is a specific inhibitor of activin A, was shown to induce muscle hypertrophy on its own but to have a more substantial, synergistic effect upon codelivery of an AAV vector expressing the MSTN propeptide directly inhibiting (myostatin/GDF-8)MSTN and GDF-11 . Now , REGN1033 induces muscle hypertrophy, and although blocking activin A with REGN2477 has a minimal effect when administered alone, REGN2477 greatly potentiates the anabolic effect of REGN1033 on muscle when they are coadministered. Taking all of these studies together, it seems clear that activin A is at least one key ligand that cooperates with MSTN to limit muscle growth.
Ozempic 3.0 !! ?
First came Ozempic
that targeted one hormone as as a glp-1 agonist , then Moujaro comes out which targets two hormones glp-1/gip dual agonist…..NOW Eli Lilly’s Retatrutidetargets 3 hormones !
*domagrozumab, {-umab type drugs} that claim Myostatin Inhibition
* Stamulumab (Myo-29), developed by Wyeth Pharmaceuticals (now Pfizer), is the first myostatin inhibitor to progress to clinical trials. Stamulumab(MYO-029) is a G1 immunoglobulin antibody which binds to myostatin and prevents it from binding to its target site, thus inhibiting the growth-limiting action of myostatin on muscle tissue. •*Epitomograb : an optimized version of (SRK-015P) is a monoclonal antibody is being used. Also, a soluble activin receptor type IIB (ActRIIB.mFc), showing an increase in body weight and grip strength, an increase in muscle mass and a delay in the onset of weakness whether initiated pre-symptomatically or after symptom onset.
Dual drug combo : Myostatin inhibition was achieved by delivering an : AAV serotype 1 (AAV1) encoding follistatin (FS344) via intramuscular injection. Muscle weight significantly increased in several hind limb muscles, including the gastrocnemius, tibialis anterior, and extensor digitorum longus. So multiple medications need to be used as it has confused scientists until the past few years when they’ve identified the pathways. There was an increase also in overall body weight, but no benefit in survival. You have to take only a single dosage, (40 μg/g) of this myostatin propeptide and take low dose 10 μg/g of morpholino (PMO25), the AAV1 encoder drug to get true myostatin inhibition. The authors showed that myostatin inhibition acts synergistically with SMN-restoring antisense oligonucleotide. •Another group delivered an AAV-encoded follistatin construct to inhibit myostatin signaling. The authors observed sustained increase in muscle mass, myofiber number, and fiber diameter
Max’s Thoughts: So their are two basic types - the second class is the one that I suspect will be used in athletes and bodybuilding. (bimagrumab, ACE-031/ ramatercept, ACE-083) have a broader range of ligand specificity and are capable of blocking not just myostatin and GDF-11, but also activin A.
Some Biopharma companies like Ligand Pharma, Viking Therapeutics, and Amgen/Sanofi/Merck/Astra-Zeneca/Pfizer/Eli Lilly/Roche Moreover, several myostatin modulators have already reached clinical trial phase for a broad range of indications, including muscular dystrophy, sporadic inclusion body myositis (IBM), cachexia, aging-related muscle atrophy, obesity, type 2 diabetes, and SMA.
**MAX TIP- Lilly and Merck invested $1 billon USD upfront to see “PeptiDream’s peptides” as a way to deliver therapeutic payloads. That means all glp-1/gip/rHGH, LAGH peptide drugs will be using Peptidream’s Novel Delivery System….A Japanese BioFirm that has landed a string of deals with drug developers such as Alnylam and Takeda ! It can deliver high dose, long acting , Target peptides safely without toxicity.
Merck(a drug research & development company saw them early and invested $2.1 billion in 2015!
Every new, Novel compound showing any hope: SARMS, Peptides, Activin receptor agonists, agonists in general, myostatin inhibitors, growth factors , mimetics, partitioning agent , past AAS ever developed , THE US, AUS/NZ, Canada and EU agencies say : “THIS COMPOUND WOULD BE ABUSED BY ATHLETES AND CHILDREN WORLDWIDE!” According to IOC/WADA, followed by the FDA. LAME !!
PEDS such as anabolic steroids, gh , insulins , Beta-2 adrenergic receptor agonists , more recent FST and ACE activin/myostatin like drugs definitely work when used properly. I’ve personally watch and have watched humans and racehorses that have used some of the newer compounds (FST 344-315 , ACE-081 and 083 for over 6 years and with dramatic results. New biologicals have so many side effects including high rate of worsening a persons health. They always rattle off more side effects than benefits (as you hear on commercials…including lymphoma and death).
It’s proven that old generation AAS can be used for cancer patients male & female with far less bad side effects vs these new biological drugs.
Combined with our current Pharmacologic Tech knowledge and capabilities in increased drug bioavailability, low to no toxicity, nanotech, and Targeted Specific Tissue Drug Technology …..not to mention worldwide shared AI/Analytics and informatics based on all past and current studies compilations & design ! People need to see the value that we see versus old lies like steroids gave me brain cancer .
Max
“TRUE” MYOSTATIN INHIBITORS
**[GDF-8 basic definition is : Myostatin ] BTW
Taldefgrobep alfa (also known as BHV2000) is a modified adnectin designed to specifically bind to myostatin (GDF-8). Taldefgrobep is a fully human anti-myostatin recombinant protein that lowers free myostatin and acts as an Activin 2b receptor antagonist with the myostatin-taldefgrobep complex.
True Myostatin Inhibitor Fast Tracked !!
(Biohaven Pharma company developed it but, it is owned by Roche)
Finally Phase 3 development to increase muscle mass(mainly for the spine at this time)! Fast track designation from the U.S. FDA for taldefgrobep alfa, a novel anti-myostatin adnectin,Taldefgrobep alfa (also known as BHV2000) is a modified adnectin designed to specifically bind to myostatin (GDF-8).
How exactly does it work? It is dual-acting,
It binds to myostatin to both lower overall myostatin levels and also function as a receptor antagonist, thereby blocking myostatin signaling in skeletal muscles.
Taldefgrobep is a fully human anti-myostatin recombinant protein that lowers free myostatin and acts as an Activin 2b receptor antagonist with the myostatin-taldefgrobep complex. Adnectins are an established proprietary protein therapeutic class based on human fibronectin, an extracellular protein that is naturally abundant in human serum. They are approving it is for : “Spinal Muscular Dystrophy” as it increases spinal muscle mass and is “Anabolic”. They are giving the sick DMD patients intrathecal Injections into the spine. I imagine someone will use IM or other. “
Both (acceleron’s inhibitor drugs)ACE-031 and ACE-083 are capable of binding members of the TGF-β superfamily, including not only MSTN and GDF-11 but also activins. A third biologic in this group is *Bimagrumab (Novartis) a monoclonal antibody blocks signaling by multiple ligands utilizing both ACVR2 and ACVR2B. Max - “Even though they do not approve these myostatin drugs, sarm, AR ligand activators often (or at all), it is because they cannot openly produce a drug with “Anabolic” effects unless it is to treat a disease like Duchenne’s/MD , MS, Cancer, AIDS, Fibromyalgia and other muscle wasting diseases ending in -“atrophy”. So just because the FDA doesn’t approve it, or it fails at trials ; you have to look at the definition of why it failed.
In my experience, almost any “anabolic” compound is unapproved due to the pressure from not only the FDA/DEA/FTC but, WADA and the IOC seem to have more influence than the other 3 combined. In fact they form drug testing by urine, blood, hair before any ped ergogenic, anabolic, or stimulant is even close to hitting stage 2 trials.
Eli Lilly’s Landogrozumab (LY2495655) experimental pharmaceutical drug designed for the treatment of muscle wasting disorders. The drug did increase lean muscle mass, accompanied by a persistent decrease in fat mass by inhibiting GDF-8(Myostatin).
Term definitions:
“Myopenia” muscle loss/wasting disorders
“Sarcopenia” - age related muscle loss
“Cachexia” is muscle wasting due to cancer, AIDS/HIV, Anorexia .
History of AAS, PED’s; Newer term : APED (Appearance of performance enhancing drug) LMAO
, just the appearance! : Due to the “1990 The Anabolic Steroids Act”, which passed as part of the Crime Control Act of 1990, which placed anabolic steroids into Schedule III. In 2003, the Controlled Substance Act was amended to include prohormones (steroid precursors) since they may potentially act as steroid hormones. The Anabolic Steroid Control Act of 2004 was introduced, which took effect in January 2005. The Designer Anabolic Steroid Control Act of 2014 even added plant herbs, botanicals, or concentrate, metabolite, or extract thereof.
The lack of research studies & trials using AAS has disrupted scientific research on animals & humans. These archaic and erroneous laws based on “False & outright Fake Studies, published artices, and scare tactics have truly set us behind of what could unlock healthful therapeutic AAS/PED’s from the past using new drug forms, nano-crystallization, chemical and pharmaceutical delivery systems. Hopefully in the next decade; scheduling will change here and abroad.
Biologicals Drugs :
*Novartis’s bimagrumab was tested in 2 trials for sarcopenia in older adults and resulted in significant increases in mean lean body mass of 6%–8%.
*Regeneron’s REGN1033 for age-related sarcopenia have not yet been published, the data that have been reported show major improvements in lean muscle mass and a decrease in fat mass, post operatively- total hip arthroplasty. The patients were followed for 6 months post rehabilitation, the patients that received the stage 2 trial drug gained more than double the lean muscle than patients that received Novartis’s Bimagrumab .
Novartis’s/Versanis is in stage 2 trials of Bimagrumab in combination with semaglutide for the treatment of obesity has begun enrolling at sites in the U.S., Australia, and New Zealand.
Myl1 promoter/enhancer drug was shown to cause a hypermuscling phenotype characterized by increased fiber numbers and increased fiber sizes
A monoclonal antibody directed against the activin type 2 receptors is capable of inducing muscle fiber hypertrophy when administered systemically to adult mice. At high doses, in fact, just two injections of the ACVR2B/Fc decoy receptor can induce over 50% muscle growth over a span of two weeks , modified activin A propeptide, which is a specific inhibitor of activin A, was shown to induce muscle hypertrophy on its own but to have a more substantial, synergistic effect upon codelivery of an AAV vector expressing the MSTN propeptide directly inhibiting (myostatin/GDF-8)MSTN and GDF-11 . Now , REGN1033 induces muscle hypertrophy, and although blocking activin A with REGN2477 has a minimal effect when administered alone, REGN2477 greatly potentiates the anabolic effect of REGN1033 on muscle when they are coadministered. Taking all of these studies together, it seems clear that activin A is at least one key ligand that cooperates with MSTN to limit muscle growth.
Ozempic 3.0 !! ?
First came Ozempic
that targeted one hormone as as a glp-1 agonist , then Moujaro comes out which targets two hormones glp-1/gip dual agonist…..NOW Eli Lilly’s Retatrutidetargets 3 hormones ! *domagrozumab, {-umab type drugs} that claim Myostatin Inhibition
* Stamulumab (Myo-29), developed by Wyeth Pharmaceuticals (now Pfizer), is the first myostatin inhibitor to progress to clinical trials. Stamulumab(MYO-029) is a G1 immunoglobulin antibody which binds to myostatin and prevents it from binding to its target site, thus inhibiting the growth-limiting action of myostatin on muscle tissue. •*Epitomograb : an optimized version of (SRK-015P) is a monoclonal antibody is being used. Also, a soluble activin receptor type IIB (ActRIIB.mFc), showing an increase in body weight and grip strength, an increase in muscle mass and a delay in the onset of weakness whether initiated pre-symptomatically or after symptom onset.
Dual drug combo : Myostatin inhibition was achieved by delivering an : AAV serotype 1 (AAV1) encoding follistatin (FS344) via intramuscular injection. Muscle weight significantly increased in several hind limb muscles, including the gastrocnemius, tibialis anterior, and extensor digitorum longus. So multiple medications need to be used as it has confused scientists until the past few years when they’ve identified the pathways. There was an increase also in overall body weight, but no benefit in survival. You have to take only a single dosage, (40 μg/g) of this myostatin propeptide and take low dose 10 μg/g of morpholino (PMO25), the AAV1 encoder drug to get true myostatin inhibition. The authors showed that myostatin inhibition acts synergistically with SMN-restoring antisense oligonucleotide. •Another group delivered an AAV-encoded follistatin construct to inhibit myostatin signaling. The authors observed sustained increase in muscle mass, myofiber number, and fiber diameter
Max’s Thoughts: So their are two basic types - the second class is the one that I suspect will be used in athletes and bodybuilding. (bimagrumab, ACE-031/ ramatercept, ACE-083) have a broader range of ligand specificity and are capable of blocking not just myostatin and GDF-11, but also activin A.
Some Biopharma companies like Ligand Pharma, Viking Therapeutics, and Amgen/Sanofi/Merck/Astra-Zeneca/Pfizer/Eli Lilly/Roche Moreover, several myostatin modulators have already reached clinical trial phase for a broad range of indications, including muscular dystrophy, sporadic inclusion body myositis (IBM), cachexia, aging-related muscle atrophy, obesity, type 2 diabetes, and SMA.
**MAX TIP- Lilly and Merck invested $1 billon USD upfront to see “PeptiDream’s peptides” as a way to deliver therapeutic payloads. That means all glp-1/gip/rHGH, LAGH peptide drugs will be using Peptidream’s Novel Delivery System….A Japanese BioFirm that has landed a string of deals with drug developers such as Alnylam and Takeda ! It can deliver high dose, long acting , Target peptides safely without toxicity.
Merck(a drug research & development company saw them early and invested $2.1 billion in 2015! Every new, Novel compound showing any hope: SARMS, Peptides, Activin receptor agonists, agonists in general, myostatin inhibitors, growth factors , mimetics, partitioning agent , past AAS ever developed , THE US, AUS/NZ, Canada and EU agencies say : “THIS COMPOUND WOULD BE ABUSED BY ATHLETES AND CHILDREN WORLDWIDE!” According to IOC/WADA, followed by the FDA. LAME !!
PEDS such as anabolic steroids, gh , insulins , Beta-2 adrenergic receptor agonists , more recent FST and ACE activin/myostatin like drugs definitely work when used properly. I’ve personally watch and have watched humans and racehorses that have used some of the newer compounds (FST 344-315 , ACE-081 and 083 for over 6 years and with dramatic results. New biologicals have so many side effects including high rate of worsening a persons health. They always rattle off more side effects than benefits (as you hear on commercials…including lymphoma and death).
It’s proven that old generation AAS can be used for cancer patients male & female with far less bad side effects vs these new biological drugs.
Combined with our current Pharmacologic Tech knowledge and capabilities in increased drug bioavailability, low to no toxicity, nanotech, and Targeted Specific Tissue Drug Technology …..not to mention worldwide shared AI/Analytics and informatics based on all past and current studies compilations & design ! People need to see the value that we see versus old lies like steroids gave me brain cancer .
Max
Also, just because Acceleron didn’t get approved , does not mean it won’t work (because they have to work efficaciously on a disease like Duchenne’s (we use it for the skeletal muscle. 
