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  1. #1
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    Default Ideas for the Near Future

    Hi,
    I was just reading the forum every now and then so far, but now I feel like I should contribute something as well.
    I am a fifth year medical student and have done some in vitro research on lymphoma therapy so far. So I have a rough understanding of our field.

    For everyone who is crying that there wont be a treatment in sight for the next 15 years, I want to say that hundreds of new drugs are tested in clinical trials at every given moment for all kinds of diseases. It is not unlikely that one of them shows the side effect of preventing loss or inducing regrowth. In the field of rheumatology a wide variety of completely new anti-inflammatory drugs are comming to the market (TNF-alpha inhibitors, IL-17 inhibitors, Il-6 inhibitors etc.) for exemple.

    However, for those who are a little comfortable with the scientific side of it, I want to discuss or share an idea, that I myself most propably wonīt pursue but that will surely offer a solution in the future.

    The cure for hair loss is already found: it is simply to prevent the hair follicles from reacting with dht/testosterone. Women donīt get MPB and castrated men neither. The problem so far is simply that any treatment that prevents this interaction is not specific enough to the scalp or hair follicles. Every anti-androgen (Finasterid, Sm, Ru (the things some of you are experimenting with) will effect the whole body in some way and thereby leading to side effects that no one wants to risk (ED, depression, loss of sex drive, infertility).

    So the problem is not that we dont know how to cure it, but that we donīt know how to get a scalp specific anti-androgenic effect. Its a problem of drug delivery. Nothing else.
    Any topical solution that somehow enters your body will enter your blood stream and therefore end up in the whole body.

    A possible solution (I am just pointing into a direction with this, nothing else):

    Create a window of opportunity to induce a permanent change of the androgen-response of hair follicles, in which the rest of the body is not affected.

    A permanent change can be attained by site-directed mutagenesis. One could use RNA/DNA oligonucleotides to induce single nucleotide mutations in the gene of the androgen receptor (roughly 400 mutations are known from people with adrogen insensitivity). This method works in vitro. The efficiency of the delivery of the oligonucleotides to the cells of the human hair follicle will depend on an appropriate vector (extensive research is done in this field!) and different options are available.

    The exposure of the hair follicle(-cells) to our vector has to happen in a setting where there is no connection to the circulation system.

    Option 1: extract hair follicles (like in FUE) and incubate them with the vector in vitro. If, due to low efficiency of the oligo delivery into the nucleus, several incubation periods need to be done, one could think of implanting the follicles into the skin of immun compromised mice, who will keep the follicles alive while delivering our vector through their blood stream as often as needed. Then the androgen-resistent follicles can be reimplanted into the human scalp.


    Option 2:
    Create a local, independant circulation of the scalp for delivery of the vector. By appling strong circular pressure around the scalp, one can shut down the escape of blood from the scalp. Then one has to connect the bigger veins and arteries within this area of the scalp to a miniature ECMO machine (which is a machine that gives oxygen to the blood and has a little pump to creat a blood flow. So it is an artificial lung and heart which is usually used when the heart is out of order during surgery or at the intensive care units). This way, we create an isolated circulation of the scalp for a long time. During this time, we can deliver any drug or vector we want in high doses specifically to the scalp. If the effect of this drug is permanent (like the gene therapy mentioned above, it is a cure).

    I know that gene therapy is only FDA approved for one disease so far and that the big problem is the effiency of delivery as well as safety (usually the vector is a virus). But the hair follicle has the big advantage, that it can be taken out the body easily (or "isolated" within the body) and treated there. Kind of like they do it with stem cells of the blood already. The problem there is, that the effciency is too low. But in the mouse option, one could repeat the treatment over and over again until the desired efficiency is achieved.

    So bottom line: a cure is not that impossible after all. Every research that is done right now will contribute to finding a good cure for hair loss. Everyone who want to now if something good for mpb is happening, should keep a close eye on the development of drug delivery in gene therapy and cancer treatment. Thats where the big fundings go and thats where I think a cure can come from.

    Additional idea:
    -An antiandrogen that transiently changes to its active conformation during exposure to UV or infrared light exposure (also not impossible. One would have to wear a head with lights in it during the night

    Cheers

  2. #2
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    Addition number 2:
    http://www.ncbi.nlm.nih.gov/pubmed/?...kin+by+RNA-DNA

    Cotsarelis was a co-author of this nature paper in 2000. Here they used dna/rna oligonucleotides and partially induced (low efficiency) a gene mutation in the hair follicles of mice. As a vector they used a special lipid (Cytofect).

    If this is at least partially possible, then the above mentioned solution works 100%. Take the follicles, put them in mice, treat the mice with the oligos and cytofect several times. Then reimplant the follicles back into the human.
    All you need to do is to induce a single mutation in the gene for the androgen receptor and as a reference you can just pick one of the many that caused some poor people to have androgen insensitvitiy.

    If someone on this forum has contact to George Cotsarelis or knows if he actually is in connection with this forum somehow, it would be interesting to get his opinion on it.

  3. #3
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    You should read this topic, https://www.baldtruthtalk.com/thread...I-ve-hacked-it
    a member described something similar that you just did (introducing a vector to cause mutation on the AR receptor gene) and he was planning to experiment on himself. I don't really know what happened after...

  4. #4
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    Thanks for the hint.
    What he did was transiently stopping the production/expression of the androgen receptor (also using short DNA strands). According to his theory, one has to prevent the AR from binding to its intranuclear targets in order to not only stop further hair loss but to even reverse it. He says that the AR "gets activated" not only by dht and testosterone but also by other molecules and therefore one has to make the AR disappear altogether. Maybe there is truth to it.

    What I am suggesting is, to make the AR useless with one single treatment by permanently changing the AR-gene. If this mutation can lead to a loss of the intranuclear function of the AR, then this would achieve the same goal as mentioned by FGF11. Only that it would be permanent and wouldnt require constant injections.

  5. #5
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    1.HI TOBIAS, you cure is only to stop hair loss or even reverse the hair that have been lost?
    2.can we ,with today technology do this?
    3.can you mention same labs or scientist who can do this?
    THANK YOU FOR YOUR TIME

  6. #6
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    Hi,
    no what I wrote is simply for prevention. Not reversal. Also, I am only pointing into a direction to where a cure could be expected from as well. For some, including me, it is just fascinating to think of possible solutions ourselves. While others just want to hear: take this, do that and then you are cured by tomorrow. Both kind of people are active in this forum I think.

    Plus, it might help to understand the process of the development of a new treatment better. Better understanding=more feeling of control=less frustration.

    The closest thing ever done to this is mentioned in the paper that I posted. Maybe you have access to it, then you can check it out. Itīs interesting. George Cotsarelis is a co-author and works at the University of Pennsylia i think.
    I just donīt know if his group his pursuing a "prevention" treatment still. So maybe they could develop a good treatment protocol with the above mentioned approach, but they just donīt because they are going after the reversal of aga.

    So long story short: 1. No reversal (except if FGF11 is correct, then yes)
    2. yes, the technology is there but is not used for this purpose. Plus it would still be labour intensive.
    3. no lab is doing this (as I know), no. So you canīt ask anyone to perform this on you now.

    Donīt be mad. I think it is good to realize that a cure (the preventive one is not that impossible. Worst case, a "cure" in 30 years will help your kids to lead a hairier life if they want to.

  7. #7
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    I like theorizing about stuff as well, but I think a cure not only have to accomplish the prevention (and hopefully the regrowth) criteria but it has to be feasible and marketable with no/or very low side effect and risk profile and it has to make sense economically.

    I think researchers should focus their efforts on either donor regeneration and/or follicle cloning. If that is achieved all kinds of androgen (and injury, burn etc.) related hairloss become curable once and for all. The infrastructure is already there, hair transplants are already a 2,5 billion usd industry per year.

  8. #8
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    thanks tobias.
    So you are saying that if fgf11 theory is correct about reverse of hair it means that you theory can reverse hair too??
    I dont know if you have read all fgf11 coments in his threads, but its obvious that he is very informed and smart guy like i think you are.Except this he works in a big pharma and has acces in different drugs. Another thing is that he has tested his teory in himself,, so to conclude I THINK THAT HE IS RIGHT.
    you can exchange ideas together i hope

  9. #9
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    The problem with current synthetic implants is that the skin rejects the foreign material, but how possible do you think it is to 3D bioprint 'fake' follicles out of skin cells surrounding a 'bulb' of synthetic hair? It wouldn't grow like actual hair, but does it even need to?

  10. #10
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    Quote Originally Posted by allTheGoodNamesAreTaken View Post
    The problem with current synthetic implants is that the skin rejects the foreign material, but how possible do you think it is to 3D bioprint 'fake' follicles out of skin cells surrounding a 'bulb' of synthetic hair? It wouldn't grow like actual hair, but does it even need to?
    there is a new "bioimplant" I think it's called, that is not rejected. The only issue is that it lasts, "months to years based on the patients proper after care" so first off, it will obviously not grow and secondly, you will have to constantly have them replaced.

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