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  1. #121
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    Quote Originally Posted by Swooping View Post
    Rofl, I provided all facts. You on the other hand continue to provide anecdote after anecdote. Now you are misinforming nave13579. You really have no clue what the hell you are talking about. Also you are ignorant as hell. You don't even know how IGF works, that's the fun part. Did I insult the rep? Not really I just said right in his face that this treatment isn't going to work with very hard argumentation. We'll see anyway in a few weeks who will have the last laugh baboon .
    You also said you'd like to break my nose. So I gave you my address, and you edited your post. To answer nave's question here is Dr. Hsu's answer:

    Transdermal as we use the term just means getting it into the dermis to reach the dermal papilla of the hair follicle. It's not easy to get across the stratum corneum and the epidermal cellular layers, both of which are rate-limiting for drug delivery. I don't know if nano formulations or nano-rolling actually address the issue. And I certainly don't know of any FDA-approved indication for the use of IGF-1 injections to treat pattern baldness. Even if there were, you would need a pretty high serum level to overcome the effects of high testosterone. Presumably, normal IGF-1 levels are not sufficient or else we wouldn't be having this discussion. Our goal is to deliver IGF-1 to the DP (but not systemically) at levels that block testosterone pathway.

  2. #122
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    Quote Originally Posted by follicept View Post
    You also said you'd like to break my nose. So I gave you my address, and you edited your post. To answer nave's question here is Dr. Hsu's answer:

    Transdermal as we use the term just means getting it into the dermis to reach the dermal papilla of the hair follicle. It's not easy to get across the stratum corneum and the epidermal cellular layers, both of which are rate-limiting for drug delivery. I don't know if nano formulations or nano-rolling actually address the issue. And I certainly don't know of any FDA-approved indication for the use of IGF-1 injections to treat pattern baldness. Even if there were, you would need a pretty high serum level to overcome the effects of high testosterone. Presumably, normal IGF-1 levels are not sufficient or else we wouldn't be having this discussion. Our goal is to deliver IGF-1 to the DP (but not systemically) at levels that block testosterone pathway.
    1. http://www.worldhairresearch.com/?p=64

    RESULTS: Results were obtained from logistic regression models, adjusting simultaneously for all the measured hormones and age. Men with higher levels of testosterone were more likely to have vertex baldness (odds ratio [OR] = 2.5, 95% confidence interval [CI: 0.9 to 7.8] per 194 ng/dL increment of testosterone). In addition, for each 59 ng/mL increase in IGF-1, the odds of having vertex baldness doubled (95% CI [1.0 to 4.6]). Those who were found to have higher circulating levels of SHBG were less likely to have dense hair on their chest (OR = 0.4, 95% CI [0.1 to 0.9] per 24 nmol/L increment in SHBG]).
    2. http://escholarship.org/uc/item/2v79r893

    In summary, regulation of human hair growth by androgen is probably mediated by IGF-1 in the dermal papilla. In male scalp, high levels of IGF-1 may increase the androgen receptor activity and dihydrotestosterone levels and these result in an increased propensity for baldness.
    3. http://www.ncbi.nlm.nih.gov/pubmed/10827403

    CONCLUSION: Older men with vertex balding have lower circulating levels of IGFBP-3 and higher levels of IGF-1 when controlling for IGFBP-3 level
    These 3 studies state otherwise and provide evidence that IGF-1 is a bad factor. IGF-1 can only reach the dermal papilla through the blood and isn't synthesized within the hair follicle. Furthermore IGF-1 is evenly distributed within the blood. What does your research team have to say about these studies? I'm genuinely interested to the answer.

  3. #123
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    Quote Originally Posted by Swooping View Post
    1. http://www.worldhairresearch.com/?p=64



    2. http://escholarship.org/uc/item/2v79r893



    3. http://www.ncbi.nlm.nih.gov/pubmed/10827403



    These 3 studies state otherwise and provide evidence that IGF-1 is a bad factor. IGF-1 can only reach the dermal papilla through the blood and isn't synthesized within the hair follicle. What does your research team have to say about these studies?
    I sent them on to check out and will provide an answer when I have one. I won't purport to have their education or experience in this field, so I won't mislead you.

  4. #124
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    Quote Originally Posted by follicept View Post
    I sent them on to check out and will provide an answer when I have one. I won't purport to have their education or experience in this field, so I won't mislead you.
    I understand, thanks.

  5. #125
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    Quote Originally Posted by follicept View Post
    I sent them on to check out and will provide an answer when I have one. I won't purport to have their education or experience in this field, so I won't mislead you.
    Hey, I know you're getting hit with a lot of skepticism so I'd like to take this time to say thank you on my and the hair loss community's behalf. We respect your work and wish you all the best in it coming to fruition both on a professional and personal level. I also appreciate your composure through the whole process, I know some here can come across badly, but it's mainly due to overzealousness or frustration. Thanks again and again good luck to you and your team! Thank you for responding to our inquiries.

  6. #126
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    @Follicept, another question if you could please ask them.

    It has been pointed out in several studies that specifically some phenotypes suffer from extensive aggressive androgenetic alopecia (AGE <30 NW3+) and show low SHBG values.

    Now SHBG is decreased by IGF-1. This also means that the free androgen index will get higher. Meaning that more DHT can bind to the androgen receptor in the hair follicle if you raise IGF-1 in blood plasma. Also decreasing SHBG leads to less estradiol, a compound known to be hair protective.

    This strengthens the 3 previous studies to expect that higher IGF-1 levels are actually bad. Why do they think otherwise is my question? Thanks, appreciate it.

    1.
    AGA is the most prevalent form of alopecia in men having polygenic origin. Total testosterone levels were within normal levels did not change in cases and controls. Some of the cases had low levels of SHBG than the reference range and level were decreased significantly when compared with the controls (P = 0.007). Frequently lower levels of SHBG were attributed to the higher frequency of the polymorphism of D327N of the SHBG gene in these men.[14] While further studies have reported androgen receptor gene present on X chromosome as well as mutations in P2RY5 display variable expressivity was a factor underlying both hypotrichosis and alopecia.[15] Although testosterone levels were normal, FAI was significantly higher in cases than controls (P = 0.0006). Free testosterone accelerates gradual transformation large terminal scalp follicles to tiny villous ones causing premature AGA in genetically predisposed person.[16] This shows that FAI is the best marker of a person's androgen status as it can bind to tissue receptors.
    2.
    Hormonal Profile in men with premature androgenic alopecia
    Androgenetic alopecia especially that with premature onset can be a cause of serious psychic trauma. As far as the treatment with antiandrogens, inhibitors of 5 alpha-reductase or hair transplantation represents a heavy economic burden for the patient, we tried to exclude other hormonal causes or to find a criterion for the apt candidates for the treatment in 15 young men with premature androgenetic alopecia. Hormonal analysis discovered a significantly lower plasma level of sexual binding globulin (SHBG) and FSH and nearly significantly higher concentration of 17 alpha-hydroxyprogesterone.
    3.
    Sex hormone-binding globulin and saliva testosterone levels in men with androgenetic alopecia.

    Sex hormone binding globulin (SHBG), plasma testosterone and saliva testosterone were measured in sixty-four men with androgenetic alopecia and in forty males within the same age range without alopecia. There was a significant reduction in SHBG levels in bald men, compared with controls. Plasma testosterone levels were not raised in bald men, but their salivary testosterone levels were significantly higher than in controls.
    4.
    Abstract Sex hormone-binding globulin and risk of hyperglycemia in patients with androgenetic alopecia.
    BACKGROUND: Low circulating levels of sex hormone-binding globulin (SHBG) are a strong predictor of the risk of type 2 diabetes. Androgenetic alopecia (AGA) has been related to an increase in cardiovascular risk, but the mechanism of this association has not been elucidated. AGA can be associated with low levels of SHBG and insulin resistance, which could be related to hyperglycemia and type 2 diabetes.

  7. #127
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    Quote Originally Posted by Swooping View Post
    @Follicept, another question if you could please ask them.

    It has been pointed out in several studies that specifically some phenotypes suffer from extensive aggressive androgenetic alopecia (AGE <30 NW3+) and show low SHBG values.
    He said he's going to let us know how it goes, so I'm not sure what the point of arguing about it with vaguely (not entirely direct) studies. If there is anyone on the forum who knows that slight differences in methodologies can have drastic changes on the conclusions you can draw from anyone study.

    All that said, if historical trends persist, then, swooping, you will be right. Fortunately, they're testing it and seem to be open to communication. So lets see what happens.

    I'm curious with the Q&A between the two of you, but you're super incendiary and rude. Come on man.

  8. #128
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    Quote Originally Posted by Gerhard View Post
    Hey, I know you're getting hit with a lot of skepticism so I'd like to take this time to say thank you on my and the hair loss community's behalf. We respect your work and wish you all the best in it coming to fruition both on a professional and personal level. I also appreciate your composure through the whole process, I know some here can come across badly, but it's mainly due to overzealousness or frustration. Thanks again and again good luck to you and your team! Thank you for responding to our inquiries.
    Of course, I am happy to! We learned a lot during our NoPricks campaign from people living with diabetes. It is a tough, lifelong, miserable thing and there is no good, easy, solution. So sometimes that frustration and anger and skepticism about us gets directed to us, and I completely understand it. It's well-founded. With that said, you guys as a whole, as with the diabetes community, are overwhelmingly supportive and hopeful and I can't thank you enough. It keeps us going. Times have been real tough here at Prometheon before, and it was only remembering who we are serving that got us out of bed and up to work in order to take that day's punches. We'll keep on keepin on, and appreciate the support and communication. We are a really small team, so if I go dark on you guys, know that it is a good sign of being busy getting the product to market, not of flaking out and giving up. Like I said, we will publish any negative results and will not take any money until we are sure.

    Devon

  9. #129
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    Quote Originally Posted by Swooping View Post
    @Follicept, another question if you could please ask them.

    It has been pointed out in several studies that specifically some phenotypes suffer from extensive aggressive androgenetic alopecia (AGE <30 NW3+) and show low SHBG values.

    Now SHBG is decreased by IGF-1. This also means that the free androgen index will get higher. Meaning that more DHT can bind to the androgen receptor in the hair follicle if you raise IGF-1 in blood plasma. Also decreasing SHBG leads to less estradiol, a compound known to be hair protective.

    This strengthens the 3 previous studies to expect that higher IGF-1 levels are actually bad. Why do they think otherwise is my question? Thanks, appreciate it.

    1.


    2.

    3.

    4.
    On it.

  10. #130
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    "DHT inhibits IGF-1 at the dermal papillae.[26] Extracellular histones inhibit hair shaft elongation and promote regression of hair follicles by decreasing IGF and alkaline phosphatase in transgenic mice.[27] Silencing P-cadherin, a hair follicle protein at adherens junctions, decreases IGF-1, and increases TGF beta 2, although neutralizing TGF decreased catagenesis caused by loss of cadherin, suggesting additional molecular targets for therapy. P-cadherin mutants have short, sparse hair.[28]"

    The answer might be that even if there is plenty of IGF in the blood, dht is silencing it at the follicle. Perhaps delivering enough IGF directly to the follicle overrides this silencing action. There might be a lot of IGF in balding guys' blood precisely BECAUSE it is being suppressed in all the follicles. There's mysterious evidence for both IGF having a positive role for hair, and then a record of more IGF in balding scalp. there's surely a correlation, but as the kythera doc wrote to me yesterday, this does not imply causality. Just because bald guys have more IGF does not mean the IGF is causing the balding.

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