BMN 111 A CNP Analogue Promotes Skeletal Growth Treating Children Suffering From Achondroplasia

This was a post that I found from a new blog I discovered which seems to write about the short stature condition known as Achondroplasia which is caused usually by a mutation on the FGFR3 gene. It seems that there is a company Biomarin, a pharmaceutical company working in therapies for rare and genetic conditions, which stated that they were coming out with a drug that can treat the mutation of the FGFR3 that has been responsible for Achondroplasia. It is supposed to be the first pharmacological therapy out there for Achondroplasia treatment.

The article is taken from the blog http://tratando-acondroplasia.blogspot.com/ entitled “CNP, the first potential pharmacological therapy for achondroplasia” (the blog is written in Portuguese so using the browser Chrome would be better to instantly translate what is on the pages into English)


Under great expectations, parents and relatives of children bearing the fibroblast growth factor receptor type 3 (FGFR3) mutation, the cause of achondroplasia, have been following the news about the development of the first real potential drug therapy to treat this condition. In the last quarter of 2010, Biomarin, a pharmaceutical company working in therapies for rare and genetic conditions, announced it was planning to start the clinical research with a compound called BMN-111. BMN-111 was described as a C-type Natriuretic Peptide (CNP) analogue. An analogue is a compound (or molecule) which has a very similar structure compared to the original one, normally keeping the same properties or with enhancements to a given characteristic of that compound.

During 2011, new updates have been released and, in the last International Congress of Human Genetics held in Montreal, a poster describing the results of the BMN-111 tests made in a mouse model of achondroplasia was presented, showing impressive results in terms of the ability of this molecule in restoring the bone growth of those animals: F. Lorget et al. BMN 111, a CNP analogue, promotes skeletal growth and rescues dwarfism in two transgenic mouse models of Fgfr3-related chondrodysplasia.

December 2011, Biomarin has released new information about the pre-clinical development of BMN-111, presenting results of tests made not only in mice but also in non-human primates, a requisition for any candidate drug to be accepted as an investigational new drug (IND) by regulatory bodies such as the Food and Drug Administration (FDA).

More recently, Biomarin has also announced that it was starting the first clinical trial, a Phase 1 study, to learn how the drug acts in the human body.

Step by step, it seems that the first medicine made to help bones grow in achondroplasia is advancing in its development, an exciting perspective. But, before lighting fireworks, it would be interesting to learn more about the CNP and what we should expect about its use in the treatment of ACH children.

 The Natriuretic Peptide Family

Peptides are molecules made of amino acids, like proteins, but they are smaller and, like their larger cousins, they are also encoded in genes. Natriuretic means a property of something that causes sodium to be eliminated in the urine. The name natriuretic came after the description of one of the first recognized properties of these peptides, which is exactly promoting the elimination of sodium in urine.

The history of the natriuretic peptides begins about 30 years ago when the first peptide of the family was discovered in extracts of rat atria and for this was called atrial natriuretic peptide(ANP). Not much longer, BNP was identified in extracts of pig brains and then CNP, and as it was the third in the row, received the C-type NP name (this is a link to a good review on CNP by Olney RC). While ANP and BNP are most found in cardiac tissue and are linked to cardiac physiology and related diseases, CNP is expressed in a number of other body tissues and remarkably found within the cartilage growth plate, where it exerts the most important of its actions. This link will take you to a figure showing the three peptides.

CNP

CNP is a known positive player in the growing bone according to many studies made in animal models and also in related mutations in spontaneous human cases. For instance, genetic mutations in the CNP gene causing its overexpression lead to overgrowth. The research also showed that slight changes in the natriuretic peptide receptor type C structure (NPR-C, one NP receptor that is thought to serve as a CNP clearance system) may be responsible for the higher final height found in people from some of the Northern European countries (Estrada K et al.;Bocciardi et al.).

This peptide is expressed (produced) locally in the growth plate. When it binds to its preferential receptor enzyme, NPR-B, located across the cell membrane (in the same way FGFR3 is) of the chondrocyte, it activates this receptor, which in turn causes the activation of other enzymes in the cell cytoplasm. Interestingly, this CNP cascade of chemical reactions will then cross with one of the most important cascades responding to FGFR3 activation, the RAF-RAS-MAPK pathway (discussed here).

activated by FGFR3, the RAS-RAF-MAPK pathway will lead to one of the most well characterized consequences of achondroplasia, which is slowing down the rate the chondrocytes enlarge (hypertrophy) and mature, thus impairing the entire cartilage growth pace. By the other side, when CNP activates its receptor, the chemical messages emitted by its cascade will turn off or reduce the RAS-RAF-MAPK cascade activity, so causing an inverse action in terms of bone growth. The main observed characteristic of growth plates of ACH mice models treated with CNP is an enlargement of the hypertrophic zone of the growth plate. Take a look in this article (free access) by Drs Yasoda and Nakao, two of the most prominent researchers of CNP in achondroplasia. They tell the history and results of their research, which has strongly contributed to the understanding of CNP in achondroplasia. This article also has a very didactic graphic showing the two cascades described above.

With the reassuring results of the research by scientists like Drs. Yasoda and Nakao, it became clear that CNP could be used somehow to rescue the bone growth arrest in achondroplasia. But how?

The Japanese group developed a mouse model where the CNP was naturally produced in large quantities by the animal body, in a strategy to simulate a situation where the peptide would be given continuously to the patient. This was necessary because of the nature of CNP. Being a small peptide, it is a usual target of several enzymes present in the blood stream calledpeptidases. This is so true that CNP, after a single intravenous injection, would last less than five minutes circulating. With such a short half-life (the way scientists describe the interval of time half the quantity of a drug will take to be processed by the body) giving multiple injections would not be a clever strategy to treat any situation. So they probably thought about a therapeutic scheme where their CNP would be given trough a continuous pump infusion, in the same way other clinical conditions have been treated in the past. Their work showed CNP indeed cause bone growth in an achondroplasia +/CNP+ composite mouse model, rescuing the bone growth arrest.

However, this solution, although feasible, has a lot of practical challenges easy to foresee. Then, is there any other way we could give CNP to a child to treat achondroplasia? The answer is yes. Given the strategy announced by Biomarin, in which their CNP analogue will be given subcutaneously once a day, there are other ways. As there is no publicly available information about the compound formula or structure we can only speculate about the solution they found, but it might be related to the knowledge we have about the metabolism of the NPs. Let’s talk a little bit about this.

As mentioned above, CNP and the other related peptides are natural victims of peptidases present in the blood and other tissues. However, the most relevant of these enzymes, neprilysin, does not cleave (cut) the NPs in the same way. Neprilysin has different affinities with the NPs, being ANP and CNP more easily cut than BNP. If you visited the figure I presented above, you may have already identified the structural differences among the three NPs. BNP has two “legs” or branches leaving the main ring while CNP has only one. Evidence exists that the longer BNP branch would be the responsible to its relative resistance to neprilysin (Potter LR, free access). So, there is a chance Biomarin could have developed a CNP analogue bearing a slight modification in its only branch structure (like in BNP) that would give it more resistance to neprilysin activity. This change could give this CNP analogue more time to circulate and diffuse into the tissues and especially into the cartilage growth plate.

It looks like a very smart solution. Tests made with animals have been showing positive results (links above) and, given the FDA authorization to let them proceed to clinical trials, results have been robust enough in terms of efficacy and safety in those animal models.

Testing CNP in clinical trials

Now is the time to test the CNP analogue in humans. What we should expect about these experiments in terms of safety and efficacy?

Safety

First, as CNP is closely related to the other NPs, and that both ANP and BNP have significant effects in the blood pressure and other circulatory parameters, a strict oversight on cardiologic and other circulatory indexes must be carried on. Biomarin has showed during a public presentation in December that the CNP analogue did cause a decrease in the blood pressure in monkeys after each injection.

Second, CNP is found in other tissues throughout the body, including the brain. A recently published study by Dr Nakao and colleagues showed that CNP can influence the body weight, possibly by acting directly in the brain. The mouse model used by the Japanese group does not reproduce the real life, so their results must be understood under this context. Nevertheless, it will be important to follow patients using CNP chronically to understand this aspect of CNP.

Third, bones are not equal, some are thin others thicker. Furthermore, achondroplasia is described as a rhizomelic (rhizo means root) bone dysplasia. This means that it is recognized that proximal (to the trunk) bones are more affected that the distal ones (those in the extremities). There is a theory this could be caused by distinct influences FGFR3 would have across the skeleton, with some bones being more affected than others by the mutation. In some of the papers published by the Dr. Nakao’s group, pictures of mice treated with continuous CNP could cause the impression that had thinner spines and longer feet and tails than the control (normal, non-treated) animals. Again, here the kind of exposure those animals had was quite different of what we would expect in the real life or with a single CNP shot a day. Nevertheless, this could be a good aspect to be observed throughout future studies in affected patients.

Fourth, another aspect to be taken in account is the kind of effect the extra CNP would have in other cartilaginous tissues such as the joints, ears, nose and trachea. Although having some specific patterns, chondrocytes tend to behave similarly to the same stimuli wherever they are located, so this is also a question that will need an answer, too.

Efficacy

How will the efficacy of the treatment of CNP be measured? Growth is not a parameter easy to measure in the short term. However, there are some indexes which can be used to monitor the growth rate in children under treatment. For instance the average growth speed rates can be derived from the NCHS series. You can see how this was made by examining this Brazilian Ministry of Health guideline directed to pediatric health care which uses these derived curves (sorry, it is in Portuguese, but look at the page 21 to see the derived graphic.

Growth tends to be fast in the first year after birth and then it starts to slow down up until puberty. It is likely that in children with achondroplasia, taking in account the intrinsic growth impairment, the growth pace could be similar (actually, this would have to be proved. I am not aware of any study addressing this feature).

The idea could be to plot the already known child heights over the years and create an individual graphic. With the exposure to CNP it would be expected that the growth speed would increase and this can be better measured comparing to the previous pace and to the expected ongoing pace. This is more than just measuring the absolute height.

Another possible marker of growth could be to take measures of the four member bones or, in other words, the lengths of the arms and forearms and thighs and legs could be taken. Then, during the treatment these measures could be readdressed to look for trends in the growth pace in the different member segments. Achondroplasia is a rhizomelic dysplasia, so it would be interesting to learn about the response of the proximal bones to the treatment and also this measure would help to spot earlier any tendency for overgrowth of the extremities.

We must remember that everything in a child with achondroplasia is normal but the workaholic FGFR3. So, if the mutated receptor is compensated what we can expect in terms of bone growth? Doctors know, for a long time, the ‘catch up growth’ phenomenon, seen in several distinct clinical conditions. When the reason for growth impairment is resolved, the affected child tends to grow faster than the average for the age until an individual mark is reached and the growth normalizes. Could the catch-up growth phenomenon happen to children with achondroplasia treated with CNP? This is difficult to say, because in this case the receptor would still be active (so, in a future therapy with a FGFR3 inhibitor, the catch up growth could be expected). Nevertheless, measuring the growth speed would give an insight about this phenomenon in the context of the treatment of achondroplasia with CNP.

arrival of the CNP analogue as the first potential therapy to help children with achondroplasia to rescue, at least partially, the bone growth, is remarkable. There are several steps to be taken in this phase of its development; the drug must prove to be safe and to have the expected efficacy.  Growing more, affected children could be spared from suffering the many common interventions seen in achondroplasia, from removal of tonsils and adenoids to serious orthopedic and neurological complications. At this moment we must be rational, not presuming that the bone growth will be restored to its full potential. However, in the case of this first possible therapy succeed, a better quality of life could be expected for children with achondroplasia.

The Link Between FGFR3 and CNP Expression – Raja’s Research Summarized

Ever since the a commenter who calls himself Raja has shown me the study of the link between FGFR3 and Achondroplasia and I realized that it might be one of the easier, most promising ways that real companies have been doing to try to help at least children increase in height, I realized that I should take a more serious look at what this researcher had to say. So I asked him/her about the research they have been doing. Here is our exchange of emails.

Me —> D Inventor

Your response to one of my posts have been very interesting. I plan to write a detailed post about the study and see where it will take the research.

I have done mostly studies on fgf2 and basic fgf2, nothing on fgf 3 yet.

So can you show me the research you have been doing?
and how comfortable do you feel about coming on the podcast and explain your own research?

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What I’ve found so far.

Children: To the best of our knowledge there is currently only one company worldwide, that researches an innovative height increase therapy: ProChon Biotech (http://www.prochon.com), established in  Israel in 1997. ProChon is developing a monoclonal antibody for the treatment of achondroplasia. This antibody approach targets specifially the FGFR3-gene and hasn´t reached the stage of human clinical trials yet. If it is successful, it will only work for children with achondroplasia. – http://www.makemetaller.org/index.php/topic,578.0.html

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D Inventor —> Me

I’ll give you a summary of what I’m working on.

Basically, our bodies are designed to only grow to a certain extent – this is really why our height is determined by our genes. Growing taller than our “predetermined” height is called skeletal overgrowth. When I started researching, I found an article on CNP in which scientists increased substantially the plasma concentration of CNP, which resulted in skeletal overgrowth of the mice models (1, 2). You can really just google this for more info, but I’ve provided the links at the end of this message. I read another article which found a family with genetic mutation that caused an overexpression of the NPPC gene, which controls the expression and production of CNP (3). Basically, everyone in this family was really tall.

Another interesting article was on FGFR3 knockout, which lead to skeletal overgrowth in mice models (4). CNP works as an antagonist to FGFR3, which is evident as CNP is able to rescue achondroplasia models with constitutive FGFR3 activation.

Here’s how CNP works (just some technical information, but this is important for when we get into the pharmaceuticals specifications):

– CNP activates its receptor GC-B, which releases cGKII (5)
– cGKII works by inhibiting the conversion of Ras into Raf (look up FGFR3 phosphorylation)
– This acts as a inhibitor to the activation of the MAPK cascade. This is important to endochondral ossification as it inhibits ERK1/2 phosphorylation.

Essentially, one way that CNP exerts its bone promoting effects is through the inhibition of ERK1/2 activation (one of two pathways that are activated with FGFR3). You can really just search up “ERK1/2 inhibition” on google and see that other scientists have achieved skeletal overgrowth in mice models in which they inhibited ERK1/2.

OKAY, enough with background info. If I’m rabbling, I apologize. It’s just that there really is a lot of information on this.

Back to FGFR3 – its inhibition leads to skeletal overgrowth and it WILL increase a person’s final height. Many people with mutations that diminish FGFR3 expression have really tall stature.

So, for us, people who want to be taller, the easiest way for us to get taller is to inhibit FGFR3. The article I posted on your website discusses how there was an increase in the height of the growth plate in a person whose growth plate was about to close (or was in fact closed). This is interesting because in the article, the individual’s growth plate was reduced to a growth scar. This usually happens when the growth plate is just about to close. However, if used in conjuction with LSLJ (if this method really does cause microfractures), then it MIGHT be effective for people with closed growth plates, since it MIGHT just help regrow growth “plates” on a micro scale, and could possibly lead to a few more inches.

So, back to FGFR3 inhibition. As far as I’ve researched, this seems to be an effective method for people with open growth plates. The problem with current FGFR3 tyrosine kinase inhibitors is the lack of specificity. But, I’ve found a novel drug which seems very specific to the FGFR family, called AZD 4547. So far, at least in vitro studies, it is by far the most selective that I’ve found, towards FGFR3. The benefit of chemical inhibitors is that they target everywhere in the body, so that growth is proportional.

While I can’t really advise anyone to take this compound, I’m trying to find a synthesis method for this compound.

If you need any more info, feel free to ask.

References:

1. Chronically elevated plasma C-type natriuretic peptide level stimulates skeletal growth in transgenic mice, Source: http://ajpendo.physiology.org/content/297/6/E1339.full.pdf

2. C-type natriuretic peptide and overgrowth. , Source: http://www.ncbi.nlm.nih.gov/pubmed/19293575

3. An Overgrowth Disorder Associated with Excessive Production of cGMP Due to a Gain-of-Function Mutation of the Natriuretic Peptide Receptor 2 Gene, Source: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0042180

4. Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3. , Source: http://www.ncbi.nlm.nih.gov/pubmed/8630492

*Just a note, while it says it causes deafness, this on a genetic knockout study. Deafness is caused by a developmental defect when the mice are embryos or just as they are growing. In humans (that are mature and fully developed), with inhibition of FGFR3, there should not be any problems with deafness (to the best of my knowledge).

5. Cyclic GMP-dependent protein kinase II plays a critical role in C-type natriuretic peptide-mediated endochondral ossification. – Source: http://www.ncbi.nlm.nih.gov/pubmed/12193576

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My Response to D Inventor

Tyler noted the link between FGFR3 and CNP as well as the link between FGFR3 and ERK 1 & 2. I  have absolutely no research on ERK 1&2 and don’t even know what they are yet. I can not comment or make any good judgement on how ERK affects everything.

I’ve done the research on CNP before and the research was done by many other height increase researchers in the past from the GrowTallForum.com which is now closed. They tried to increase their height through finding compounds that could increase the level of CNP or Nitric Oxide in their systems. I found at least one patent by some Japanese guy who showed that increased CNP would help children who are suffering from idiopathic short stature.

It is very clear that there is a chance that increased CNP levels in the blood would negate the function of FGFR3 to a certain level in humans suffering from Achondroplasia. Refer to the post CNP, the first potential pharmacological therapy for achondroplasia

From that post, it states “Biomarin, a pharmaceutical company working in therapies for rare and genetic conditions, announced it was planning to start the clinical research with a compound called BMN-111. BMN-111 was described as a C-type Natriuretic Peptide (CNP) analogue.

So from this article, it shows that there is still a lot of options and hope for kids who are still growing . CNP does not have to be the only option.

I read over the article you referenced quite extensively entitled “Cartilage Dysplasia and Tissue Mineralization in the Rat Following Administration of a FGF Receptor Tyrosine Kinase Inhibitor”

I wanted to first make the point that the study was done on lab rats, not humans. It might not even be able to be translated to humans. The reason for this is like I said before, mature rats still have growth plate cartilage.

In the paper, the mature mice were defined to be around 11 months old. I googled the term “at what age do rats stop growing”. The information is mixed but the general answer is that they usually stop growing around the 8-10 month range. Refer to RatForum.com. So technically the “mature” rats in the experiment should have stopped growing in bone length.

The paper does say that the cartilage in the mature rats did go through hyperplasia. However, the main point and problem I would bring up is that unlike humans, even mature and old rats (and possible mice) still have bands of cartilage in their limbs. The long bones of old rats are not completely bone, but have portions that are stil cartilage. Humans don’t have that physiology. Our limbs become all bone except at the ends.

Remember that most of the people who ever ask about how to grow taller already have their plates fused. They are already in a very difficult position when they start to ask for help and look for solutions.

What happens usually is that while a person is still young and have open plates, even if they are short they still rationalize in their mind and hope that they just haven’t gotten the chance to go through their growth spurts yet, even if they never will get one. Everyone hopes that they would be one of the lucky ones who gets to go through a 6-7 inch growth spurt and that would happen to them. For most people, that doesn’t happen. So they wait and don’t do much except wish and hope, and they run out of time when the cartilage is all gone. After they notice that they are still short even after puberty, then they start worrying since they never got the growth spurt that they ‘deserved’ or expected to get and start to search. It is already too late.

Me and the other researchers have found multiple ways for children with open growth plates get taller. That is easy. Finding a way for fused cartilage has been the problem, and will always be the problem. That is the real solution we want to find.

What we always focused on was a solution for people with bone maturity, because we all understand that ultimately, that is the real solution.

 

Increase Body Regeneration Ability Through Knockout of Genes Controlling Wnt Beta Catenin Pathway

In a very recent article published on the website for the magazine Scientific American entitled “How to Regrow a Head – A single gene switch makes worms regenerate their whole bodies from their tails” it seems that scientists have figure out how to potentially increase the regenerative ability of animals by knocking out certain genes that have been regulating the Wnt and Beta-Catenin Pathway.

Now, we have researched and studied both the Wnt and the Beta-Catenin Pathway just to learn much more about molecular biology and biology. Post were written…

The Connection Between The Wnt Beta Catenin Signaling Pathway And Growth, Part I

There was also some research done on the PI3K and AKT pathway in the post “The PI3K, AKT And mTOR Signaling Pathway”

The facts are that for most people who have ever taken a molecular biology class, or done some graduate level work on studying cells, they would be quite familiar with the Wnt-Beta-Catenin pathway and the PI3K-Akt pathway. These pathways are some of the most well known and extensively studies extracellular signaling pathways in cells.

For the article itself, I would guess that the news is not a big shocker for anyone who has been studying the Wnt- Beta-Catenin pathways for a while, but for people who are not in the field, it might seem crazy and be new information. From the article, here is a recap of what these genes and signaling pathways do…

…Wnt genes, which code for a series of enzymes that relay information from outside the cell to the nucleus, eventually producing proteins called β-catenins, which regulate gene expression…

Genes create a type of protein known as enzymes which help chemical reactions and biological process occur in cells. For the Wnt genes, they create a type of enzyme that will going to affect how signals and kinases that come to the surface of the cell from the outside wil do to the stuff inside the outer membrance. The end result is another type of protein known as Beta-Catenin, which regulates what types of genes are expressed.

In the experiments the researchers wanted to find out if a lack of Wnt gene expression was responsible for the poorer regenerative abilities in particular worm species. What they found was that “… in wounds that did regrow heads, genes coding for a series of enzymes involved in the Wnt pathway had their expression turned up”

Now, the gene that causes the regenerative properties seem to be modulate/controlled by other types of proteins. If these other proteins are themselves inhibited, then the regenerative ability of the animal beng studied should increase. “…both teams found that by suppressing a gene that regulated Wnt function in their flatworms, they could get chunks of the normally non-regenerative tissue to grow fully functional heads”

There was actually three studies, three experiments, three groups of researchers, and three papers submitted to whatever prestigious journal is in the field of their expertise. The 3rd team located in Japan, noted that they found out that another signaling pathway, the extracellular signal-related kinase (ERK) pathway also had a function in regenerative abilities. 

One of the scientists “Umesono suggests that the effects of ERK proteins and Wnt proteins counteract each other. If the Wnt pathway dominates then it signals tail growth, but if ERK suppresses its influence then heads can form”

I have also done some research on the ERK pathway in the post “The Mitogen-Activated Protein Kinase, MAPK And Extracellular-Signal-Regulated Kinases, ERK pathway

These proteins created just make sure certain genes are either turned on or off, and the rate at which expression does (or does not occur).

Implications For Body Part Regeneration

Since the Wnt, Beta-Catenin, and ERK pathway is already understood quite well, it would not be too hard to try to knockout the genes that controls the expression of the pathway, and create people with altered genomes which allow them to heal body wounds much faster and more efficiently than the regular human.

Implication For Height Increase

If we can get our own bodies to develop regenerative abilities through genetic engineering, it would be very easy to increase our height. All that is needed to be done to get a new layer of growth plate cartilage is to make a distraction in the bone, and the wound would start to form blastema which can then be controlled using differentiation modulators into the cartilage that is needed.

Body Hack XXII: Using Gene Therapy To Cure Baldness

In the same article Cosmetic Gene Therapy’s Thorny Traits which was written back in 1997, the writer Rick Weiss notes that the branch of genetic engineering or biomedical engineering known as gene therapy would help not just people who wish to change the color of their skin but also cure an affliction that is exhibited by many men.

It seems that gene therapy can be used to cure baldness.

From the article… Potential Gene Therapy for Baldness

A cream could carry hair growth genes in laboratory-made bubbles called “liposomes.”

1. Cream would be rubbed into the scalp.

2. Liposomes would be absorbed into the skin, where they bind to dormant hair follicle cells and release their genetic payload.

3. Genes would enter follicle cells and turn on hair growth machinery. Hair would continue to grow for as long as the new genes continue to function inside cells.

SOURCE: Anticancer Inc.

A San Diego company that specializes in getting genes into hair follicles already is developing a gene-laden lotion that would be rubbed into the scalp to reverse baldness. It’s also experimenting with genes that will make gray hair grow dark again and to make straight hair grow curly — a truly permanent permanen

“Genetic enhancement is going to happen,” said University of Southern California gene therapist W. French Anderson. “Congress is not going to pass a law keeping you from curing baldness.”

The article itself was not written to show people who feel bad about themselves how to use breakthrough technologies to give themselves cosmetic enhancements, but to question the ethics of using some types of biomedical technologies.

Note: Since this is a website dedicated to doing research on the science of height increase, we have to talk first about how to apply the principles of biomedical engineering and genetic engineering to help children , and possibly adults, increase in height and what that might mean.

The issue of height is a sensitive subject for people like baldness. Both issues revolve around the fact that humans care a lot about their appearances. Most people want to be taller, and most people don’t wish to loss the hair on their head. When people end up shorter, or become bald, most people would believe that they became less attractive.

For men, being both short and bald can greatly decrease one’s reproductive chances and reproductive opportunities.

However, I can say with confidence that curing baldness will be much easier than finding a way to increase height. If we analyze how hairs originate and the locations where they originate in, we realize that all that is needed is a germinal hair follicle that needs to get stimulated.

I may not know enough gene therapy yet, but I could suspect that something as simple as the application of a cream in the scalp of bald people with hair follicles and stem cells inside would cause the right cells to go on the area of baldness. Then a growth factor (maybe follicle stimulating hormone should be used???) is added to get the germ cell to start to replicate and grow out in the right direction.  From tissue engineering principles, it is possible to just grow a layer of skin with hair on it, and then graft that skin to the scalp. There is a lot of ideas and proposed ways to treat hair loss.

There is actually a lot of options these days for guys (and girls) who have insecurities and issues with their hair loss and want some type of option.

The article that is referenced showed that even back in 1997, there were companies coming out that would be able to cure baldness. Using the technology of gene therapy, they would even be able to knock out the genes in an adult male that is causing baldness and get replaced with genes that result in thick, lush hair. For more information on how the basic process of gene therapy works, refer to the Wikipedia article on Gene Therapy.

For baldness, it might be completely cured for the entire human race within a century if we really wanted to implement gene manipulation.

Body Hack XXI: Use Gene Therapy To Change A Person’s Skin Color

Back when I was in high school, which was over a decade ago, I remember reading about the racial oppression suffered by Africans and African Americans by “White” people decades and centuries ago. In some stories, it talks about how some slaves developed such an inferiority complex from being treated so badly by their masters, or how some black people being abused by the whites during the segregation periods would try to change their skin color using extreme methods.

Stories would come out where young black kids and older women and men would scrape their skins with rough surfaces until their skin would bleed hoping that they might be able to scrape away the darkness in their skin. The psychological desire to change their skin from dark to light was so strong, and it might have crippled their ability to ever fully accept themselves and have the self confidence to not be defined by the color of their skin.

Ever since people have met other people from different parts of the world and realize that one group of people is different from another by the shade or tint of their skin, some minority of people have probably wished that they could change the color of their skin.

It seems that only now, in the beginning of the 21st century with the advent of gene therapy, it might be possible now to really change one’s skin color for good.

Warning: As an individual, I do not promote or condone this technology. The desire to want to change one’s skin color, to look either darker or lighter is each person’s own opinion. I am only an amateur researcher presenting scientific possibilities that most people might not be aware of. Ultimately, science and technology is neither good or evil.

There was an article called “Cosmetic Gene Therapy’s Thorny Traits” (By Rick Weiss, Washington Post Staff Writer Sunday, October 12, 1997; Page A01) back in 1997 which showed that it has been possible to change one’s skin color for a long time.

He writes….

As a medical researcher, Scott McIvor never suspected that his efforts to develop new cures would lead him to the edge of a brewing bioethical storm. Then, a few months ago, he got an e-mail message from a doctor who wanted McIvor to help him change a patient’s skin color…

…in gene therapy, in which researchers inject healthy new genes into patients in an attempt to treat genetic diseases. The doctor knew that genes affecting skin pigmentation had already been identified, and he had a patient who wanted to change his racial appearance

…Changes in skin color and muscle mass probably could be accomplished with current technology, they and others said. But the possibility of harm would be difficult to justify for a cosmetic procedure and, more important, genetic enhancement of healthy people raises a host of difficult ethical questions.

Analysis

I almost never write these Body Hack posts anymore since discovering unique ways to hack or enhance our human bodies was never the true goal of this website. However, sometimes I find something that is so unique that I felt compelled to share it.

The ability to use gene therapy to change one’s skin color completely is one of them. I have done a lot of research on seeing whether it is even theoretically possible to use gene therapy in some way to increase a person’s height so I understand at a very basic level how gene therapy works.

After studying over the article written above, and looking back at how a basic gene therapy would go, it seems that it is indeed possible for people to change the color of their skin.

From gene therapy, the basic idea is to take some cells from a person, put the cells in a culture, surgically remove the gene that they want to delete or cut out, or use a vector with the mutation or slightly altered gene added into the cells in the culture, and have the culture put back in the person’s body.

The thing is that scientists have found out which gene causes the pigmentation of the skin, which is what determines whether a skin will be dark, darker, light, or lighter. All that will need to be done to get a dark skin or light skin is to combine the vector with the altered gene with a cell with the unmodified gene removed and the result are cells of the person who will have one gene of the entire chromosome changed. The cells are then added back into the body through a transfusion where the new cells are going to completely replace the old cells with the unmodified gene.

The result is that from the change in gene, the overall physical characteristics of the person will change over time.

I am quite aware that there are many cultures that really prize lighter or whiter skin, like in India where the product known as Fair & Lovely (and Fair & Handsome) are extremely popular to make women’s (and men’s) skin lighter. It is a social, psychological and anthropological issue.

While I have shown in this post that it is indeed possible, for over a decade now that genetic engineers can indeed change a person’s skin color using gene manipulation, the issue is really ove r the social consequences of such a thing.

What does it mean to us as human beings to allow for maybe thousands of people to go through with cosmetic surgery to change their skin color?

I and the other height increase researchers may have extreme difficulty in accepting the height we were given by our parents and genetics, but can we at least just accept at least our skin color and race?  

Michael Jackson 1I am left to wonder whether it was gene therapy that caused the now past Michael Jackson to change the color of his skin from the natural brown color that he was born with to the extremely white and pale skin he had when he passed away years ago. The article was written back in 1997 and it was said that most scientists working on gene therapy knew that it could be possibly done to change one’s skin color.

With the amount of money that Michael had back then, being so rich and popular, it is not inconceivable to believe that he would try to do such a controversial and radical cosmetic feature as to change his skin color.

I have no idea whether this world wide super star entertainer would ever have an identity issue over the color of his skin and whether he ever had any difficulty in being ‘black’ but I know that almost everyone loved him and had no problem with him being african american.

The official statement was that Michael Jackson’s incredible skin color transformation beginning in the 80s was due to a skin condition known as vitiligo. Recent evidence from autopsies and doctors show that Michael did have vitiligo. However I am left to wonder how was it possible that Jackson’s vitiligo would be so evenly distributed throughout his entire body. I personally have seen many people with the condition of vitiligo but usually the whiteness comes in patches on the face or skin.

Why Growing Taller With Closed Growth Plates Is So Difficult To Figure Out And Impossible To Almost All People

I wanted to explain where height increase researchers are in terms of development and why it has been so difficult to figure out how to achieve this goal of trying to grow taller after the growth plates in a person have closed.

Many times I have written posts hypothesizing what was the limiting factor or the real problem in figure out a solution to this thing that 99% of visitors to this website is looking for.

I had first tried to explain what exactly was really limiting us as researchers in the post “What Exactly Are The Critical Elements, The Rate Limiting Parts?In that post, I had suggested that we move away from studying too much on GH (somatropins) or IGF-1 and focus more attention on growth plate formation through using growth factors and chondrocyte differentiation from the progenitor mesenchymal stem cells. At this point, I still agree with this idea.

In another post I had copied a study which showed that no matter what happens, our bodies are designed by evolution to be limited in size. At some point, we will stop growing, if we are reasonably healthy and don’t suffer from certain genetic disorders. The post was “Mechanisms Limiting Body Growth In Mammals

A few days ago while I was eating dinner with my girlfriend, she started to ask me what exactly I was doing when I spend hours each day doing research and obscure scientific papers. I have not revealed this website and my research to her yet and I want to keep this part of my life hidden. However she persisted and asked me more probing questions about this issue.

(Side Note: Now, I am currently living in Seoul, South Korea and at that moment we were eating this dish at a local eatery which is Pig Feet, known in Korean as Jokbal. While the sound of the idea of eating the feet of pigs may not sound too appetizing to some people who were raised in the western world raised on lean beef, pork chops, and chicken breast, it turns out that it is really good and surprisingly good for a person who believes in the Paleo Diet.)

I glanced at the food in front of us, which was just meat bones and I managed to come up with a very simple explanation of what it was that I was doing without revealing her the entire scope of the research.

I picked up a leg bone of the meat in front of us and showed her that in the limbs of mammals, there is two types of structural tissues, bones and cartilage. She understood that much.

I then said that all that my research is trying to do is to try to convert bone tissue into cartilage tissue. That is what I have been trying to do.

I indicated that what I was trying to do was create a band of cartilage through the entire cross section of the long bone.

Bone Tissue —> Cartilage Tissue

From this simple concept is how the entire height increase endeavor can be summed up. Now, the way that the natural process works is the reverse process. Cartilage Tissue into Bone Tissue.

Cartilage Tissue —> Bone Tissue

If one would like to read on why and how cartilage tissue turns into bone tissue, I refer to the PubMed study “Cartilage begets bone versus endochondral myelopoiesis“. Analogously, cartilage tissue, at least hyaline cartilage, is almost always surrounded by a layer of progenitor cells that have not differentiated yet called perichondrium. In the same way, bone tissue at least in long bones are surrounded by a bilayer of cells known as periosteum.

The process that happens in nature is perichondrium turns into periosteum. 

What we are trying to do is create a simple, non expensive way to start a process that is exactly the opposite or reverse process of a natural process.

  • Bone Tissue —> Cartilage Tissue (going against nature)
  • Cartilage Tissue —> Bone Tissue (how nature works)

To grow taller, we can do only four things that I can think of currently. We are either…

  1. Stretch the bone tissue
  2. Implant something into the bone tissue that can stretch out
  3. Implant a device in cavities between bones that determine height
  4. Turn the bone tissue, at least part of the bone tissue, into cartilage tissue

Option #1: Stretch the bone tissue

First, I had looked into the idea of just how feasible was the idea of just getting some weights or some traction device to stretch out one of the bones in our body to make us taller.

Since human height is determined by the following bones in the human body… skull bone, the vertebrate bones, from cervical to the coccyx, the hip/pelvic bone, the femur, patella, and tibia/ulna, and talus with calcaneus… these are the only bones that we need to worry about.

I would assume that no one would want to stretch out their skulls so that it out of the question. For the vertebrate bones, that is reasonable but the bones are irregular, and if we try to pull the bones too hard, we can cause serious problems to the surround tissues, most specifically causing intervertebral disc problems like bulging discs or herniated discs. Given just how common herniated discs and lower back pain is to humans, I am currently not going to pursue the idea of trying to stretch out the irregular vertebrate bones just for cosmetic reasons.

This leaves just the idea that maybe we can figure out how to stretch out vertically the pelvic/hip bone, the leg bones, or bones in the feet. Since the pelvic bone and feet bones are irregular, it might not be very feasible to stretch the bones even in a laboratory setting. How would the pelvic bone even be held by a mechanical device to stretch it out?

So the only bones that are left that have any possibility of being stretched comes back to the long bones.

I tried to do a rough calculation of just how much loading must be done to the adult human femur to pull it beyond the range of elasticity and lead to some form of deformation.

The post where the real calculations were done on was…

The Values For The Magnitudes For The Forces And Loads Needed To Increase Epiphyseal Cartilages Thickness And Human Femur Bone Without Fracture (Important)

From taking the measurements of forces done from tensile loading on the cartilage of young lab rabbits, I did two extrapolations calculations to reach the answer that to stretch out the human long bone in the legs, specifically the thickness, strongest one, the femur, it would take between 29,000-32,000 lb of force to pull the adult human’s long bone apart.

My calculations seem to be actually reasonable close to what was guessed to be the needed tensile values of human bone by other researchers who did real experiments with the leg bones of cows. Their proposed values for ultimate yield strength of human femur bones was 150 MPA (Mega Pascals) which when converted into the American unit of force, the pound-force, or pound, is 22,000 lbs. For certain engineers, getting a final calculated value within even 50% to what it is supposed to be is good and I am guessing that the values between mine and other researchers are close enough to start to support the idea that a tremendous amount of force is needed to pull the strongest bone in the human body beyond it’s ultimate yield strength point.

Years ago there was another serious height increase seeker and researcher named Sky who tried to induce height increase their hanging weights on his ankels to try to lengthen the tibia with 15-30 lb weights on each leg. He did not succeed. The rough calculations shows that his method would not have worked. He would have needed to use weights that were 100X in weight to have a chance of pulling the tibia bone apart.

Important Note: The way that the tensile loadings work is that successively smalls increment of weight is added over time to the material being tested. If we instead tried a type of loading that was not slow and linearly increased, like a fast jerk, it might be possible that it would take less weight and force to cause the bone to snap or fracture into a lengthened state.

If the calculated values are correct, which involves the unit of lbs in the 5 digits, then where would the average person with limited resources even be able to find devices that can product a stretching/tensile load that high?

Even regular sized 4-door sedans are only around 4,000 lbs. Adult bull African Elephants, the largest land animals in the world are at 8000-10,000 lbs only. It might be interesting to imagine holding one part of the long bones in the leg in place and having a weigh attached and have a 3 full sized elephants or 6 cars get on on the scale.

What type of device can the average person get their hands on to generate that much force? I don’t know whether there are any mechanical devices that can do that without also being associated with a very high risk for severe injuries that would lead to a person being crippled for life.

Some people talk about using electrical field or magnetic fields to pull the bone apart. An idea that was recently talked about was using an induced magnetic field to pull two metal implants further apart in the post “A Method To Distract Bone Slowly Using Magnetic Fields, Metal Implants, And Acidic Solution”. I personally only gave a general idea on how it might work. Much more research would have to be done to see how reasonable lengthening bone using electromagnetic fields are.

Even if it was possible to get a device that can generate that type of force, there is an extremely high chance that instead of experiencing plastic deformation by the bone the bone due to how brittle it is, would just fracture and snap in two pieces. Remember that the calculated value was for the Ultimate Yield Strength for the bone from looking at it in a Material Sciences perspective.

In the post “The Concept Of Youngs Modulus, Stress, And Strain Explained For The Application Of Bone Tensile Loading Or Bone Stretching (Important)” we looked at the engineering terms of young’s modulus, yield strength, ultimate yield strength, and other terms to explain just how “brittle”, elastic, and deformable was the human bone.

stress-strain-curveWe know that in general the human bone is brittle, especially when it is taken out of the body, and left in normal air conditions which lead to the bone lossing water, dehydrating it, causing it to loss whatever little elasticity it did have.

Note that the picture to the right is one of the general stress-strain graph of materials.

From an in vitro perspective, human bones are too brittle to have a large enough range of strain values to be able to get to what can be called the perfect strain region. We know that if the amount of strain is increased to a point which is below the yield strength, it will just snap back in place since bones are technically elastic, but it is just that the deformation in terms of length from a tensile load is almost negligible. If the amount of loading is increase too far, it would go past the ultimate yield strength, and the bone would fracture, and fracture so badly that the person basically pulled their leg off.

While the graph to the right is very general and is used as a diagram to show how the stress-strain relationship really works, because the bones are so brittle, there should be almost no range for the material science term called “necking”. Not only that, the range between yield strength and ultimate yield strength might be so small, that the yield strength is the ultimate strength. What if there is no range for a tensile load which would get the bone to the plastic deformation and not to the range where major fracturing would occur.

Option #2: Implant something into the bone tissue that can stretch out

I had made a note of the idea that maybe the biggest problem is not the bones themselves, but the surrounding tissue, the muscle that is causing most of the difficulties in the post “The Rate Limiting Tissue May Be The Surrounding Muscle, Not The Bone”

The one of the most common difficulties with replying to people who wish to increase their height as adults is that they state that they are willing to try almost any idea except go through with the option of surgery, specifically the limb lengthening surgery.

I had expressed and ruminated about the issue of the need to always distract bone to increase height superficially in the post “Is Bone Distraction Or Bone Breaking Always Needed To Increase Height?

Anything involving an implant would most likely be invasive, and that means that the person can no longer do the needed steps in the privacy and comfort of their homes, away from the public judgement of other people. The desire to not reveal who they are is a very big concern for people who try to increase their height. Most people I ask to come on the podcast and speak say no. They are afraid of the social repercussions of the possibility that someone that they know would hear their voice and reveal this side of themselves.

One could say that maybe it would just be smarter to implant newly grown or explant growth plate/cartilage into the bone, but that would still require that a section of the bone broken apart. If that is the option that a person would suggest, maybe it would be smarter, and less invasive to figure out whether we can turn the bone tissue already there into cartilage tissue. That option, option #4 is the one that I and other researchers would like to figure out.

Option #3: Implant a device in non bone cavities between bones that determine height

This idea is actually a little more credible than some people might believe.

I did a recent post about this idea when a regular reader showed me this revolutionary surgical procedure where a titanium stent is implanted into this cavity in the feet of human which is made of only ligaments, with no bone tissue. The post was “Do People Get Taller From Flat Foot Corrective Surgery With A Hyprocure Implant?”

It seems that there was a guy who wrote a blog talking about how his condition of flat feet made him decide to get a feet implant to decrease pain in his legs and back. As a result of the surgery, he noticed that he became half an inch taller.

So what other cavities that are between bones can we theoretically implant something to make ourselves taller?

The first thing to realize is that for most cavities between bones, they are filled with some other type of tissue, like ligament, cartilage, or extracellular fluid (like the cerebral spinal fluid)

The most obvious location would be the synovial joint of the knees. However, I am not sure how many people who wish to become taller would be willing to implant any type of metal into their knees just to be a few cms taller. I know that there is a chance that getting some aggrecan or hyaluronan injections into the synovial cavity may lead to less diurnal variation as the day goes on but I am not aware whether there is any type of device that any researchers have been doing to get height increase their knee implants.

If we try to find other joints or cavities which can be expanded, I am left to wonder maybe it is reasonable to try to hypertrophize and expand the thickness of the intervertebral disks. Technically, the disks are cavities between the vertebrate bones since the definition I am using is that the term cavity implies any space between bones that determine the overall height that is not consisting of any bone tissue. The disks are made from different types of collagen and some cartilage so they are ‘cavities’ as defined for this unique application.

This is actually the idea that most people have on how to explain why using traction, inversion machines, stretching, yoga, rolfing, all lead to permanent or temporary height. You are NOT stretching out bones, but stretching the cavity/non-bone tissue that contribute to the determination of one’s height.

Option #4: Turn the bone tissue, at least part of the bone tissue, into cartilage tissue

So if we don’t like the idea of breaking the bones through surgery to get at least the initial distraction, if we can’t get the type of machinery or device to exert upwards of 30,000 lbs of tensile force, and if we have no cavities that we would be willing to accept to get metal or plastic implanted into our body, then the last thing is to try out is whether we can turn the bone tissue that is in our body into cartilage tissue.

Remember, all that I have really stated is that to expand volumetrically a very tough, hard object that is not very elastic and brittle, there is only 4 things that we can do try out.

  1. Use brute force with pliers and pull the ends of the tough material and hope that it does go through with plastic deformation with completely fracturing and breaking in half.
  2. Put a cut, laceration, distraction, fracture, or a physical break in the object and then stretch it using the same devices we would use in the first option. This idea would involve the actual object being broken but the amount of force needed to pull it apart to expand the overall structure’s size volumetrically decreases dramatically.
  3. If there are any spaces within the object which is not already filled by the material, put something in the space that can push out the object around it and potentially make it bigger.
  4. Turn a part of the material into a another type of material with completely different material properties. With our intended situation, we want to make the bones turn into some other material that can still be strong enough to hold up a person who can be over 200 lbs but also have the plastic elasticity needed to be pulled/expanded using a reasonable amount of needed tensile load.

I hope as researchers we never forget that the reason the extremely hard bones can even lengthen at all in the first place is because in the beginning, the tissue was not bone, which is extremely hard and brittle. In the beginning, the type of tissue was cartilage, hyaline cartilage.

It is hyaline cartilage which has the right type of mechanical qualities which makes it possible for humans to even go through a type of somatic growth as vertical growth. The entire process of endochondral ossification revolves around cartilage tissue, NOT bone tissue, although the end result or output of the endochondral ossification is bone tissue.

It is cartilage that is between two parts of bone tissue which get expanded out due to the fact that the microscopic cells in the cartilage extracellular matrix tissue (the chondrocytes) start to actually expand in volumetric size, and by doing this, they push the entire matrix and the entire matrix gets bigger, like a loaf of bread that gets baked in the oven.

When the chondrocytes hypertrophize, while the effect for themselves is get bigger by maybe 5 X, the effect the cells have on the tissue outside the outer cell membrane is that the organic and inorganic composition that forms the matrix gets pushed farther apart from each other. If we used a microscope to do a histological examination, and we took pictures of a set of points (A, B, C) and then noted the distance between those points, and then noted the distances between the same points but now after the chondrocytes have hypertrophied (A’, B’, C’) we would realize that the 2nd measurements on average would have gotten bigger apart. The main point is that when the cells in the cartilage matrix expand/ or puff out, they puff out the entire cartilage.

(Another good analogy is the idea that as the distance between the galaxies get farther and farther apart, we can say that technically the size of the known universe, as defined as all the space that the galaxies can reach, is get bigger)

This means that the entire ability of bones to get longer is from cartilage tissue.

Technically, it might be possible to lengthen bone if the cells of bone, the osteon, the osteophytes, and osteoblasts could go through their own type of hypertrophy where they expand out and get bigger, but there does not seem to be any way for them to do that, at least not that I known of.

This shows that maybe the easiest option in terms of simplicity of concept theoretically is the last one, where we just replace the bone tissue to cartilage tissue, but also possibly the hardest option to actually execute and implement correctly.

  • We know that physicians can land have increased the length of long bones using the 2nd option, where a break in the bone is done in the beginning, so that the external device can actually pull the bone apart.
  • From the Hyprocure Stem Implant, we know that the 3rd option has also been done and is also successful in giving a small amount of increased height.
  • I and other researchers have seen that that many height increase seekers and researchers have tried the 1st option, what I call the brute force method, and none of them have succeeded. I propose now that the reason that the idea of just stretching a bone does not work is because the amount of force needed is much, MUCH more than what was used before.

In some ways, we can view endochondral ossification as an internal process that causes the cells in the bone-cartilage matrix to push the entire structure outward. The cells inside the cartilage is pushing the tissue outward from the inside. It might be that maybe we can figure something out that can get the bone cells, the osteoblasts to expand outward in a specific direction, and get into a columnar formation.

Now, I am fully aware that for people who wish to grow taller, then want something easy, simple, cheap and something that they can implement and do alone in their homes without other people finding out. This means that for most people, the idea of breaking the bone is rejected almost by all seekers. So distraction of even a section of the bone is something people refuse to consider.

Surgery for most people is just out of the question. They are willing to try anything else, just not surgery. I completely understand this way of thinking and sympathize with everyone since it is generally accepted that the surgery that does lengthen bone is very expensive and painful.

Everyone wants something non-invasive and wish for a magic chemical compound that they can swallow. I wrote about this problem in the post “There Is No Magic Bullet”. The fact that nearly everyone wanting something that is non-invasive or minimally invasive makes the situation extremely hard. 

Even with the case where scientists and researchers can regrow a completely functional growth plate, many people still will not accept this approach because to get the new growth plates, their limbs will still need to be operated on to get the growth plate cartilage implanted into the bone and that would involve distraction still.

This shows just how difficult our searching and research are. Due to how people want certain things in certain ways, and refuse all other options, it seems that even with a breakthrough like showing that functional growth plates have been already been grown in vitro, which I had wrote about in the past “Engineering Growing Cartilage Tissue In Vivo Through Chondrocyte Transplantation (Big Breakthrough!)”, people will still be searching for something better because they are still not satisfied. 

I am reminded of a conversation I had with a superior at a company I had interned at during the summer after my sophomore year in university. The company’s goal was to develop a way to disrupt the normal viral vector- cell membrane process that occurs in AIDS. They were trying to cure AIDS. At the time, the only way that the scientists could figure out how to deliver the drug was through it getting released into the blood stream through a needle injections.

My superior made the side remark that if a competitor company who was also trying to figure out the right release patterns of dispersion for the same compound could create an oral version, none needle version of this treatment, the company would get destroyed. The conversation showed me that when it comes to medical treatment or any type of cure to solve a problem, people want something easy, something that doesn’t require any type of work. For humans, swallowing a pill to cure AIDS for them was a much better option that getting a syringe-needle subcutaneous injection to cure AIDS. People wanted the best, easiest option for themselves. In the process, I feel like too many people try too hard in emailing me asking me for some magic or secret technique or formula to help them grow taller.

At this point, I could send an email reply telling a person to ingest mercury (Hg) at 5 mg per day to grow taller, and some people just might be willing and actually do carry through with it to get it.

WARNING: The previous suggestion is something that WILL NOT WORK. I was just using the idea as an example of a crazy suggestion/reply to people’s emails, which people might think was the ‘magic secret’ which would make them increase in the 9-10 inches that they want. Well it won’t work. Don’t swallow mercury.

At this point, I would think that to really satisfy the people’s desires, we have only two options.

  1. We figure out how to get a band of bone tissue in the long bone to turn into cartilage.
  2. We try to figure out whether we can get bone cells, osteoblasts and osteocysts (or whatever other living cells in the bone matrix) to hypertrophize like the chondroctyes in growth plate cartilage. 

Option #1: We figure out how to get a band of bone tissue in the long bone to turn into cartilage.

The first idea would be the one that could be more likely to work out. I think that at this stage, the limiting step or weakest link of our research is figuring out just how to get the bone tissue to turning to cartilage tissue. Again, remember…

Bone Tissue —> Cartilage Tissue

As long as we can get the bones to turn into cartilage, I am going to propose that everything after that should be relatively easy.

I realize that maybe the easiest type of cartilage to form would be the fibrocartilage, the type of cartilage that is formed when one drilled through the subchondral layer of bones, and hit the marrow in the intermedullary cavity, which will start to spurt/leak out and then the mesenchyme in the marrow start to differentiate into cartilage, but a type that is not as strong or good as the hyaline cartilage that we really want.

However, I suggest that we first just figure out how to go from bone tissue to fibrocartilage first, and then try ot figure out how to go from fibrocartilage to the better hyaline cartilage.

The second thing to figure out if we do manage to turn bone into cartilage, is how to get enough chondrocytes in the cartilage to start to proliferate. However, I say that this step should be relatively easy by just taking some explanted chondrocytes and using a syringe injecting them into the cartilage.

To get the chondrocytes that are injected to start to proliferate , we just add a growth factor mixture, something like BMP-7 with TGF-Beta1-3 through another injection.

The last big thing to work out once we do get the chondrocytes to start proliferating is how to get the chondrocytes to start to get in the right alignement, to form the columnar formation which allows to actually push the cartilage longitudinally. However it turns out that we have discovered that the compound Thyroxine seems to cause the chondrocytes in the natural growth plates to get into the right direction/orientation for long bone longitudinal growth. This was talked about in the post “Thyroxine Regulates The Morphogenesis Of Isolated Chondrocytes Into Columnar Cartilage (Big Breakthrough)”

At this point, I suspect that the process of chondrocyte hypertrophy is almost always automatic after the chondrocyte reach the later stages of life when they are ready to go through apoptosis.

I also am going to assume that the tissue interface between cartilage and bone will always be continuous and should run smoothly in causing cartilage to vascularize and mineralize.

This is why I am saying that after we get the right compound added to the converted cartilage tissue to get the chondrocytes implanted inside to align into columns, the rest can take care of itself. (However I could be wrong about the assumption on the cartilage-bone interface and the fact that chondrocytes will always go through a hypertrophy stage releasing alkaline phosphatase)

Option #2: We try to figure out whether we can get bone cells, osteoblasts and osteocysts (or whatever other living cells in the bone matrix) to hypertrophize like the chondroctyes in growth plate cartilage.

The truth is that this idea of trying to make the bone cells in the cortical bone and trabecular bone of our limbs to start to expand in size, just like what the chondrocytes in growth plates do is something that I just proposed today.

After finding the studies by much researchers do did mechanical tensile loading testing on cow leg bones from 100 years ago stating that the amount of force to actually pull a long bone is around 30,000 LBs, I started to move away from the idea of ever being able to lengthen boen using brute force.

I personally don’t have a robot or device that can pull in opposite directions with over 30,000 of force in a very linear increasing fashion. I also don’t want to risk the possibility that if the loading of such a force gets increased too fast, my leg might snap in half and I become crippled for life, or even loss a leg or limb.

This means that if the height increase seeker wants to really find a non-invasive or minimal invasive approach, they are going to need somehow turn on the components that are already in the bone matrix to start to puff themselves up and possibly increase the bone size.

They will have to stimulate what is inside and get that to push outwards, instead of trying to use mechanical, electrical, or chemical devices and which will apply stimuli externally.

At this point, I am not even sure how to get started on this type of research yet, since the idea came only today.

I am aware that there are some types of bone cells that do get bigger and go through hyperplasia, but I have always associated it with metastatic tumors that get out of control or the formation of bone spurs on the surface of bones by osteoblasts that start to proliferate and hypertrophize too much in the adult human.

Now, I and the other researchers are quite aware that even if we can get the bone cells to start to expand, the cortical bone matrix with the calcium minerals embedded might be very resistant from expanding like cartilage matrix, which is much softer and elastic.

This is why I am proposing two idea on how to ‘soften’ the bones to a point where maybe the targeted bone region can be softer than the surrounding bone tissue.

1. Adding Ascetic Acid/ Vinegar/ A Weak Acid

 

Adding a weak acid to remove the calcium apoxyapatite which might be similar to a normal acid-bad reaction which neutralizes the targeted area. I wrote a post about the fact that if you put bones  and put them a few days in vinegar (composed of ascetic acid), the calcium minerals that make bones hard get removed, leaving just the collagen, and the bone as a result turn into rubber, and that bone tissue can definitely be stretched out.

The post was “Using Acids To Induce Reverse Ossification For Calcium Mineral Absorption”

2. Adding PTHrP/ PTH in the right dosage to turn the bone such soft enough while having enough strength to keep the integrity of the overall boen structure intact.

In one of the most important posts I have written, I showed that the compound PTHrP would be critical in causing chondrocytes to not completely differentiate, reverse differentiate, and can be used in combination with growth factors and other compounds to generate cartilage and demineralize the bone matrix, making the overall thing softer and more malleable.

The post was “Parathyroid Hormone And Parathyroid Hormone-Related Protein May Lead To Non-Invasive Epiphyseal Growth Plate Regeneration (Big Breakthrough)”

The other post that was the original source is “The Connection Between Regenerating Deer Antlers and The PTHrP, PTH And IHH pathway for Cartilage Regulation, PTHrP Seems To Be The Answer (Big Breakthrough!)”

So it seems that the other idea, which I am not sure how feasible, is to get the bone cells to expand and push themselves against the bone matrix and lacunae and possibly get the bone to increase volumetrically.

Overall Conclusion

The thing to realize is that what we want and what is even theoretically possible does not agree with each other. There really is not a lot of options to the individual.

What the average person would love to do is just swallow some strange chemical concoction and end up taller within a few months but that just won’t happen, at least for people with closed growth plate.

Everyone who messages me want something easy and cheap that they can do in the privacy of their own homes.

I look at something like the Lateral Synovial Joint Loading technique that Tyler who writes for HeightQuest.com has been proposing for over 5 years now and I would say that it definitely would be the best, most clever idea for a “height increase hack” I’ve seen so far.

There is some evidence that it might work and there is also evidence that says that it won’t work, that the experiments done on rats can not be transferred and applied in the same way to the human body.

Beyond what the LSJL can offer, Someone recently sent an email to me asking whether I knew if “there’s something more potent that the guy at home can do?” I say NO.

HOWEVER, there might be something that can be done along with LSJL which can greatly increased the chances of it possibly working. What might help with the lateral loading was this idea I had proposed where a person can remove tension from the covering of the bone to let the germinal layer of the periosteum to potentially turn into the chondrogenic lineage and push out/ elevating the entire bone structure just slightly.

I wrote about the original idea in the post “An Alternative Explanation On Why The LSJL May Actually Help People With Closed Growth Plate Increase Height And Grow Taller (Big Breakthrough!)”

The idea of using another instrument, a hammer and chisel, to cause a tear in the periosteum to decrease bone layer tension to increase the chances of LSJL was expanded a lot more through the video post “The Chisel And Hammer Supplement Technique Explained Through Video”

For The Future

There is nothing we can do to get around this thing, at least right now. The research will focus almost exclusively on learning more about how the underlying mechanism for somatic work is currently understood. That involves a lot of research on endocrinology.

Interestingly, I recently started to learn much more about anatomy, physiology and pathology and tried to take a USMLE Step 1 Practice test just for fun. Out of the 322 total problems on the test (46 questions for each section with 7 total sections), I got only around 60 questions right, and that was sad since it was a multiple choice exam with at maximum 5 possible choices for each question (sometimes 4 options). If I had just chosen A for all of the questions, theoretically I should have gotten around 64 questions right. Note that to pass the USMLE Step 1, a person needs to have a score of 188 or better, the average pass rate is around 97%, the national average is around 220-225, and that to get into the most competitive fields like Radiological Oncology or Plastic Surgery, one needs to get a score around 243-249.

(Side Note: For the potential physician, a good resource from the National Resident Matching Program to see just how well they need to perform on these standardized tests to get matching for the speciality that would like to focus on in their medical career is located HERE.)

I don’t plan to ever be a physician any time soon since I find the field of medicine rather boring. However, I do read up a lot more on medicine and biology as well as genetics these days, unlike my undergraduate days when I hated anything related to biology.

I understand that at this time my knowledge on the human body and its numerous ways to go bad is severely limited compared to well trained medical school students.

There is no way to see into the future. I know that the idea of using stem cells combined with tissue engineering can lead to a alternative to limb lengthening surgery to lead to height increase in adult humans. That approach would definitely work but it is important for the seeker to remember to get something like an implant of a new growth plate to start growing again, they would still need to go to the hospital, talk with a surgeon, and get some type of surgery, which would be invasive. Is that okay for humans or would they want something better, because maybe we just can’t figure out something better.

Side Note: After doing the research for over 1 year, it turns out that there is at least a dozen methods and ideas which would help adolescents and children with open growth plates to increase their somatic growth which are mostly inexpensive, not too time intensive, and non invasive. There is definitely A LOT of hope, options, and chances for children to increase their growth rate and final adult height if they (or their parents) want to make themselves taller. I do plan within the next 2 years to write s seminal work on describing just what is possible for people with open growth plates from analyzing the real science of growth.