Big Breakthrough: Vosoritide to grow taller

Update on Vosoritide:  New studies have come in about it that show very promising results and I am like 99% confident that it would work on children that do not have dwarfism because they also are impacted by CNP and have FGFR3 receptors.   Vosoritide is very promising and I think will eventually be used for children of normal growth velocity.

Vosoritide is basically a daily CNP injection.  It’s targeted for dwarfism but as everyone has FGFR3 receptors it can work normal children but testing would be needed.

<-From the video it seems that it’s progressing very slowly.  Which is unfortunate as it has potential to happen normal children and possibly even adults.  Unfortunately it doesn’t seem like they’r keen on testing Growth Hormone and CNP at the same time because Growth Hormone may only increase growth velocity but not final height but perhaps together.  They address other potential uses kindof at around the 25 minute mark.

Here’s more on CNP.<-“we developed transgenic mice with an elevated plasma concentration of CNP under the control of human serum amyloid P component promoter and exhibited that these mice showed prominent skeletal overgrowth phenotype”

CNP delays mineralization.->”The femur, skull, and spine (L2-4) measurements were longer than that of the wild-type littermates”  It could potentially affect adults via spinal height even if limbs do not increase.

CNP activates bone turnover and remodeling in vivo

More on CNP.<-also there’s a snippet from free patents online for CNP being used to increase height in people free of FGFR3 abnormalities meaning normal children.

Who knows if CNP could potentially increase height in adults until it is tested….

Apparently Biomarin did test this on adults but did the adults get taller?  Although the study was only for a short period of time approx two weeks which is not a lot of time to evaluate if the adults grew taller.

Note Meclozine has been associated with height growth too.

Note based on this image, barring other effects the benefit of CNP is limited based on how much growth inhibiting effects FGFR3 induces.  Though according to Dose dependent effect of C-type natriuretic peptide signaling in glycosaminoglycan synthesis during TGF-β1 induced chondrogenic differentiation of mesenchymal stem cells., CNP may induce differentiation of MSCs to chondrogenic lineage so it’s effects may not solely be limited based on how much FGFR3 there is to inhibit.

“A multinational study of 35 children (5–14 years of age) receiving daily subcutaneous vosoritide at a dose of 15 µg/kg demonstrated a sustained increase in the annualized growth velocity of approximately 1.5–2.0 cm/year over 42 months of treatment.” Let’s say that’s 1.5 inches over 3 years.  That’s pretty significant.  How long that can be sustained will be revealed with further testing.

Here’s another study on Vosorotide:

Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial

Methods: This randomised, double-blind, phase 3, placebo-controlled, multicentre trial compared once-daily subcutaneous administration of vosoritide with placebo in children with achondroplasia. The trial was done in hospitals at 24 sites in seven countries (Australia, Germany, Japan, Spain, Turkey, the USA, and the UK). Eligible patients had a clinical diagnosis of achondroplasia, were ambulatory, had participated for 6 months in a baseline growth study and were aged 5 to less than 18 years at enrolment. Randomisation was done by means of a voice or web-response system, stratified according to sex and Tanner stage. Participants, investigators, and trial sponsor were masked to group assignment. Participants received either vosoritide 15·0 μg/kg or placebo, as allocated, for the duration of the 52-week treatment period administered by daily subcutaneous injections in their homes by trained caregivers. The primary endpoint was change from baseline in mean annualised growth velocity at 52 weeks in treated patients as compared with controls. All randomly assigned patients were included in the efficacy analyses (n=121). All patients who received one dose of vosoritide or placebo (n=121) were included in the safety analyses. The trial is complete and is registered, with EudraCT, number, 2015-003836-11.

Findings: All participants were recruited from Dec 12, 2016, to Nov 7, 2018, with 60 assigned to receive vosoritide and 61 to receive placebo. Of 124 patients screened for eligibility, 121 patients were randomly assigned, and 119 patients completed the 52-week trial. The adjusted mean difference in annualised growth velocity between patients in the vosoritide group and placebo group was 1·57 cm/year in favour of vosoritide (95% CI [1·22-1·93]; two-sided p<0·0001). A total of 119 patients had at least one adverse event; vosoritide group, 59 (98%), and placebo group, 60 (98%). None of the serious adverse events were considered to be treatment related and no deaths occurred.”

1.57cm is small but significant.  And major if it can be maintained throughout development.

Here’s another study on Vosorotide:

Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study

“Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported.

Methods

After completing at least six months of a baseline observational growth study, and 52 weeks in a double-blind, placebo-controlled study, participants were eligible to continue treatment in an open-label extension study, where all participants received vosoritide at a dose of 15.0 μg/kg/day.

Results

In children randomized to vosoritide, annualized growth velocity increased from 4.26 cm/year at baseline to 5.39 cm/year at 52 weeks and 5.52 cm/year at week 104. In children who crossed over from placebo to vosoritide in the extension study, annualized growth velocity increased from 3.81 cm/year at week 52 to 5.43 cm/year at week 104. No new adverse effects of vosoritide were detected.”

Now growth velocity does not always coincide with final height.

“Due to the inherent variability of growth and the lesser magnitude of the pubertal growth spurt in children with achondroplaisa, these long-term effects will only be known once these children reach final adult height”

Efficacy of vosoritide in the treatment of achondroplasia

“Achondroplasia is the commonest form of dwarfism and results from a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene on chromosome 4p16.3. The mutation is at nucleotide 1138 resulting in a G-to-A transition (134934.0001). This condition is characterized by full penetration meaning that everyone with this genetic mutation will exhibit the phenotypic characteristics of achondroplasia. It is a gain-of-function mutation that causes increased inhibition of cartilage formation. C-type natriuretic peptide (CNP) acts on the growth plate through the natriuretic peptide receptor-B (NPR-B) causing the transformation of guanosine 5′-triphosphate into cyclic guanosine monophosphate. However, CNP cannot be used in the treatment of achondroplasia because it is rapidly degraded by neutral endopeptidase. Vosoritide is a modified recombinant human CNP and has a half-life 10 times that of CNP. Clinical trials have demonstrated that vosoritide is effective in significantly increasing the annualized growth velocity in children with achondroplasia before the fusion of the epiphyses.”

<-couldn’t get this full study.

16 thoughts on “Big Breakthrough: Vosoritide to grow taller

  1. Strike_Poseidon

    Look… Tyler or Minigolfer, we need to talk a lot more I have tried making post on LSJL forum but you for some reason do not respond there at all now, now I will say one thing right now. Xcrunner on the old grow tall forum mentioned using CNP’s and KSBGF’s as another way to grow taller even for adults right? CNP expands the hypertrophic zone of the growth plate, Alkoclar even mentioned before that structural loss was because of the loss of KSBGF’s ( BDNF and BMP derivatives, a group of diverse growth factors and proteins secreted by the kidney) combined with CNP raises cGMP and cGMP has been shown to increase overall size of growth plate. Studies have shown the meclozine has shown to be just as good as CNP if not better for stimulating all the same effects like inhibiting FGFR3 but from what I recall from a study on FGFR3 deficient mice, they had raised Ihh expression, all of the BMP’s and it even downregulates the NOG gene which encodes for the noggin protein so that is even better for our case as for the KSBGF’s : https://evolutionarymuse.com/products/bmp this has kaempferol and kaempferol has been shown to raise KSBGF’s.

    Now what we also need is potent pi3k stimulation since it is specifically osteoblast proliferative, since puerarin spray forum isn’t really available right now we need hexarelin and si wu tang for that now and we also need to hypermethylation our DNA to optimal levels (not excessive) because from my research it is very important for another way to induce pituitary tumors like gigantism or leukemia, but SAM-dependent methylation for people with inactive plates takes 6 months to a year to reactivate them, this so we can reverse our growth plate senesensce to peak pubertal growth spurt conditions. All of these interventions together give the most OP stack ever as these people put it: https://grow-tall-forum.proboards.com/thread/14/research?page=1&scrollTo=185
    FGF-2 upregulation is what alkoclar is mainly aiming for and he made a 26 year old grow 11 cm with that kind of intervention my full stack is more powerful than that

    These interventions are getting tested by quite a lot of people right now by the way, there is a new kind of grow tall forum now but it is a forum for improving your overall looks or the incel community: https://looksmax.me/threads/the-ultimate-pubertymaxxing-guide-an-introduction-into-androgens-and-growth-factors-and-how-to-apply-them.97140/page-12
    A lot of people are trying it, even people like Wincel who used to be part of Hakker’s research team is on that site but made a few outdated methods because Hakker’s method is quite outdated in general this is a combination of xcrunner’s and hakker’s methods but I have provided loads of my own research there too, your ‘senior researcher’ can have long time to scruitinise

    the final stack recommendation is hexarelin, si wu tang, meclizine, the BMP formula, SAM-e (2g enteric coated tablet), folic acid,folinic acid, glucosamine chondroitin msm easily most powerful stack

    1. Tyler Post author

      Right now I’m focused on mechanical methods. There’s tons of theories but you can’t know for sure until you test and it’s hard to test chemical methods.

  2. LouisSarkozy

    glad to see your still posting and active. So do you think it could theorically increase people with closed growth pplates height via spinal increase or does it only works on people with open growth plates?

    thanks and hope you’re doing fine

  3. Wax

    I will start my stack soon:
    -Diosgenin 300mg
    -Dioscin 300mg
    -Icariinn ~200mg
    -MK677 25mg
    -Meclizine 25 mg
    -polysaccharides Lycium barbarum ??mg
    -MSM ??mg
    -D3+K2 (MK4 not MK7) ??mg

    1. Strike_Poseidon

      bro lmao what u doing on this site. add sam-e folic acid and folinic acid to that as well bro otherwise i doubt you’d gain much also you need potent pi3k activation since puerarin isn’t around i would suggest u take si wu tang and hexarelin as well

  4. Wax

    Diosgenin, Dioscin and Icariinn recommended Can Can Alkoclar. MK-0677 increases and maintains elevated IGF-I levels. Meclizine blocks FGFR3. Polysaccharides Lycium barbarum increases FGF-2 levels.

  5. Abdias soares

    What’s the likelihood of this injection working on adults in your opinion

  6. dan

    Have you explored other options? I remember reading something about an Israeli company in the comments to one of your previous posts

  7. Bobby Liu

    Hey Tyler, I hope you continue working on this. Congratulations on your new discovery! I love reading your work, thank you for inspiring future hope 🙂

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