Understanding Androgenetic Alopecia

[Fena2000]

So people with androgen insensitive androgen syndrome are the opposite of us. Cant they look at those peoples genetic makeup to find a cure for us. Sounds dumb I guess.
God, I don't know what sucks more being insensitive to androgens or being sensitive to it. I think I would go with insensitive, for women it doesn't look that bad, but for guys, uhh, not so good.

Androgenetic Alopecia is way to complicated to cure, the only cure would be genetic editing, but that won't happen in our lifetime.

 

[hellouser]

Androgenetic Alopecia is way to complicated to cure, the only cure would be genetic editing, but that won't happen in our lifetime.

1) People said Alopecia Areata, Totalis, Universalis were all too complicated to cure... and look with JAK inhibitors are capable of doing. Too bad that the 1% of hair loss sufferers get a treatment before the other 99%.
2) Brute force implanting newly created follicles from stem cells courtesy of either Dr. Lauster, Dr. Jahoda or Tsuji Labs will be a cure. Bonus points to Tsuji Labs if they manage to create an injectable solution of cells rather that requiring implanting of already grown follicles like a regular hair transplant.

 

[Fena2000]

1) People said Alopecia Areata, Totalis, Universalis were all too complicated to cure... and look with JAK inhibitors are capable of doing. Too bad that the 1% of hair loss sufferers get a treatment before the other 99%.
2) Brute force implanting newly created follicles from stem cells courtesy of either Dr. Lauster, Dr. Jahoda or Tsuji Labs will be a cure. Bonus points to Tsuji Labs if they manage to create an injectable solution of cells rather that requiring implanting of already grown follicles like a regular hair transplant.

So if they are able to clone and integrate the sebacous gland , then the puzzle is solved. But from what I've read, if they have a cure , it wont be affordable for the average joe. So that's no hope for us either, by the time it's on the market and we can afford it , we will be sitting in a elderly home playing cards, and probably not even remember we have no hair because we're too demented to even know.

 

[hellouser]

So if they are able to clone and integrate the sebacous gland , then the puzzle is solved. But from what I've read, if they have a cure , it wont be affordable for the average joe. So that's no hope for us either, by the time it's on the market and we can afford it , we will be sitting in a elderly home playing cards, and probably not even remember we have no hair because we're too demented to even know.

Hence why reform with clinical trials using OUR OWN stem cells is absolutely necessary. Picture this:

Phase 1, 2 and 3 trials take a 1-2 years each with time inbetween and an additional 2+ years for approval from the FDA. That comes to around 10 years (ridiculous). All of that also requires many more years of research before trials start..

But the biggest problem in all this is this:


If the trials take up to 10 years... what does 10 years tell governing agencies that 3-5 years do not? Why are these arbitrary numbers there for something that isn't arbitrary like results from new treatments? Furthermore, the FDA is a giant pain in the *** as it stalls release anyway... but yet they want to know safety? How can you tell if a treatment is safe if people dont actually USE it? The whole system is fvcked... it needs to change.

 

[Fena2000]

Hence why reform with clinical trials using OUR OWN stem cells is absolutely necessary. Picture this:

Phase 1, 2 and 3 trials take a 1-2 years each with time inbetween and an additional 2+ years for approval from the FDA. That comes to around 10 years (ridiculous). All of that also requires many more years of research before trials start..

But the biggest problem in all this is this:


If the trials take up to 10 years... what does 10 years tell governing agencies that 3-5 years do not? Why are these arbitrary numbers there for something that isn't arbitrary like results from new treatments? Furthermore, the FDA is a giant pain in the *** as it stalls release anyway... but yet they want to know safety? How can you tell if a treatment is safe if people dont actually USE it? The whole system is fvcked... it needs to change.

I dont know if the EMA works the same as the FDA, but it's a pain for sure. It would make me furious if I or one of my kids would have a deadly disease and there's a cure within reach, but it needs approval of the FDA. Nice but by that time I or my kid could be dead.
But the FDA is not to blame, its those annoying people suing companies because of sideefects of some products.

 

[hellouser]

I dont know if the EMA works the same as the FDA, but it's a pain for sure. It would make me furious if I or one of my kids would have a deadly disease and there's a cure within reach, but it needs approval of the FDA. Nice but by that time I or my kid could be dead.
But the FDA is not to blame, its those annoying people suing companies because of sideefects of some products.

There needs to be some disconnect between suing and and taking the treatment. Like an agreement that any 'pre-approved' treatment will not be subject to legal battles by the consumer. It's like Japan's conditional approval for stem cell treatments DURING phase 2. Gotta give MAJOR credit to the japanese in this sense.

 

[Fena2000]

There needs to be some disconnect between suing and and taking the treatment. Like an agreement that any 'pre-approved' treatment will not be subject to legal battles by the consumer. It's like Japan's conditional approval for stem cell treatments DURING phase 2. Gotta give MAJOR credit to the japanese in this sense.

Totally agree

 

[Swoop]

1) People said Alopecia Areata, Totalis, Universalis were all too complicated to cure... and look with JAK inhibitors are capable of doing. Too bad that the 1% of hair loss sufferers get a treatment before the other 99%.
2) Brute force implanting newly created follicles from stem cells courtesy of either Dr. Lauster, Dr. Jahoda or Tsuji Labs will be a cure. Bonus points to Tsuji Labs if they manage to create an injectable solution of cells rather that requiring implanting of already grown follicles like a regular hair transplant.

Indeed something along the line of option 2 would be great and the ultimate answer. It just sucks we are probably the "last" generation who struggles with this problem.. Just really in the transitioning zone now.

 

[Fena2000]

Indeed something along the line of option 2 would be great and the ultimate answer. It just sucks we are probably the "last" generation who struggles with this problem.. Just really in the transitioning zone now.

Wish they could speed things up a little.

 

[Swoop]

Wish they could speed things up a little.

I concur .

Another study;

 

[Mach]

Maybe we need to look at animal hair growth products. Maybe there's a product that can make a horses mane grow faster and fuller. I use a gel that's made for horses on my foot for the tendinitis. works better than any prescription.

 

[paulie72785]

Hi new guy here with a bit of science background(completed High school).I read the whole post(skipped the huge *** words and confusing names) and i must say F.U.C.K.I.NG. GREAT JOB MAN coz this article while a bit confusing on detailed info (VEERRRYYY) has made me think a bit so i was thinking if i could post what i learned and you guys could correct me??Ok so here i go
1.their are two guys:-balding and non balding
2.The balding one have a dermal pappilae which is weak and has easily startled Abdrogen Receptors but not the NON BALDING BASTARDS......
3.Now to treat Androgenetic Alopecia we would have to find a way to UPGRADE our dermal pappilae towards the androgen sensitivity
4.Before DHT has sex with the bitchy pappilae we have to put a barrier(Any INFLAMMATION chances???)
5.KILL THE ANDROGEN RECEPTORS......IMO
5.minoxidil and Tricomin are just plain pointless coz they are not treating the Androgenetic Alopecia but just keeping the hair follicle aliVe (YEAH I WAS THAT DUMB....THANK YOU FORUM MEMBERS) just like a Coma patient on life support......
Did i get it right???

 

[Kirby]

Swoop, do you see the possibility of any new treatments emerging in the foreseeable future? Lurking BTT I see you were not optimistic about CB.

 

[Swoop]

@Pauly thanks and yes you are right in your assumption that "upgrading" our dermal papilla niche would be the ultimate answer. We just managed to culturing dermal papilla cells, now we need to find a way to do that without losing gene expression. If they crack that we get really close to a cure.

Swoop, do you see the possibility of any new treatments emerging in the foreseeable future? Lurking BTT I see you were not optimistic about CB.

Don't get me wrong if it really works without getting systematically and being devoid of side effects then it will be a great treatment to use as a tool to slow/stop Androgenetic Alopecia. Especially for the guys suffering from side effects, cause current treatments like finasteride, dutasteride, ru all pose the risk of side effects. However even cutting your balls of won't reverse Androgenetic Alopecia, and RU58841 is just as strong and probably even a bit stronger than CB-03-01. Currently I don't see a real "cure" coming in the near future, however there are some treatments emerging to aid even more in fighting Androgenetic Alopecia, so that's good. Also the positive side is that we are beginning to understand Androgenetic Alopecia more and more, up to all the molecular pathways implicated in cycling.. Also cell based therapies are developing at a rapid rate etc.

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This goes well with this story;

[video=youtube;0klARAxOYiI]http://www.youtube.com/watch?v=0klARAxOYiI[/video]

Another study ;

Background: Clinical evidence shows that accumulation of 5 α-dihydrotestosterone(DHT) in dermal papilla cells(DPCs) is implicated in androgenetic alopecia. Objectives: To determine whether DHT affects cell growth, cell cycle arrest, cell death, senescence, and induction of reactive oxygen species(ROS), and whether these effects aremediated by microRNA(miRNA)-dependent mechanisms. Methods: We measured cell viability and cell cycle, detected ROS, and performed senescence-associated β-galactosidase assays in normal human DPCs(nHDPCs). Further, we performed miRNA expression profiling using miRNA microarray to determine whether changes in miRNA expression were associated with the cellular effects of DHT. Results: We found that DHT decreased cell growth by inducing cell death and G2 cell cycle arrest and by increasing ROS production and senescence in nHDPCs. 55 miRNAs were up-regulated and 6 miRNAs were down-regulated in DHT-treated nHDPCs. Bioinformatic analysis showed that putative target genes of these up- and down-regulated miRNAs were involved in cell growth, cell cycle arrest, cell death, senescence, and ROS production.

Conclusion: These results demonstrate that miRNA expression is altered in DHT-treated nHDPCs and suggest a potential mechanism of DHTinduced cell growth repression, cell cycle arrest, cell death, senescence, and ROS induction.

 

[paulie72785]

How about we could just fry our Androgen Receptors......That would solve it all

 

[Swoop]

Another study which relates to this (on mice though this one);

Overview of major pathways implicated in Androgenetic Alopecia in relation to senescence and an overview about how they work in general;

Senescence-inducing signals, including those that trigger a DNA-damage response (DDR), as well as many other stresses (Fig. 1), usually engage either the p53 or the p16–retinoblastoma protein (pRB) tumour suppressor pathways. Some signals, such as oncogenic RAS, engage both pathways. p53 is negatively regulated by the E3 ubiquitin-protein ligase HDM2 (MDM2 in mice), which facilitates its degradation, and HDM2 is negatively regulated by the alternate-reading-frame protein (ARF). Active p53 establishes the senescence growth arrest in part by inducing the expression of p21, a cyclin-dependent kinase (CDK) inhibitor that, among other activities, suppresses the phosphorylation and, hence, the inactivation of pRB. Senescence signals that engage the p16–pRB pathway generally do so by inducing the expression of p16, another CDK inhibitor that prevents pRB phosphorylation and inactivation. pRB halts cell proliferation by suppressing the activity of E2F, a transcription factor that stimulates the expression of genes that are required for cell-cycle progression. E2F can also curtail proliferation by inducing ARF expression, which engages the p53 pathway. So, there is reciprocal regulation between the p53 and p16–pRB pathways. Interactions among ARF, HDM2, p53, p21, CDKs, pRB and E2F also occur in other cell contexts — for example, during the DDR and reversible or transient growth arrest — so it not yet clear how senescence, as opposed to quiescence or transient growth arrest, is established. It is noteworthy, however, that at least in cell-culture studies, upregulation of p16 is not part of the immediate DDR and does not occur during transient growth arrests or quiescence.



Next time I'll probably write about how minoxidil & 17b-estradiol (estrogen) relate to these pathways and might exert their effects.

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How about we could just fry our Androgen Receptors......That would solve it all

It would indeed, if you could invent a way to destroy the androgen receptors in the dermal papilla selectively that would be a permanent prevention cure for Androgenetic Alopecia.

 

[Joxy]

[h=1]Activating hair growth with a little help from the skin[/h]
A group from the Spanish National Cancer Research Centre (CNIO) has discovered an unexpected connection—a link between the body's defense system and skin regeneration. It turns out that macrophages are involved. These are cells from the immune system that are in charge of devouring invading pathogens, a process called phagocytosis. The authors report that macrophages induce hair growth by surrounding and activating cells in the skin that have regenerative capacity, called stem cells. The discovery that macrophages activate skin stem cells could influence technologies with potential applications in tissue regeneration, aging, and cancer.
The authors of the study are Mirna Perez-Moreno and Donatello Castellana, from the Epithelial Cell Biology Group of the BBVA Foundation-CNIO Cancer Cell Biology Programme, along with Ralf Paus, a hair immunobiology expert from the University of Manchester and Münster. "We have discovered that macrophages, cells whose main function is traditionally attributed to fight infections and wound repair, are also involved in the activation of hair follicle stem cells in non-inflamed skin," says Perez-Moreno.
These findings emerged from an observation by Perez-Moreno while she was working on another research project. Intriguingly, the mice she was working with at that time started to regrow hair when they were given anti-inflammatory drugs. Curious as to whether close communication between stem cells and immune cells could explain this observation, the Perez-Moreno lab began to test different types of cells involved in the body's defense system for a role in hair growth. They observed that when skin cells are dormant, a fraction of macrophages die naturally due to a normal process called apoptosis. Surprisingly, the dying and surviving cells activated nearby stem cells and hair began to grow again.
Macrophages secrete a number of factors including a class of signaling molecules called Wnts. Importantly, when the researchers treated macrophages with a Wnt inhibitor drug, the activation of hair growth was delayed—demonstrating a role for Wnt from macrophages in promoting hair growth. Although this study was carried out in mice, the researchers believe their discovery "may facilitate the development of novel treatment strategies" for hair growth in humans.
The researchers used tiny droplets, or liposomes, to carry the drug used in the study. The future use of liposomes as a way to deliver a drug to specific cells is promising and may have additional implications for the study of several pathologies, says Donatello Castellana.
From a more fundamental perspective, this research is an effort to understand how modifying the environment that surrounds adult skin stem cells can regulate their regenerative capabilities. "One of the current challenges in the stem cell field is to regulate the activation of endogenous stem cell pools in adult tissues—to promote regeneration without the need of transplantation," says Perez-Moreno.
Because of this study, it is now known that macrophages play a key role in the environment surrounding stem cells. "Our study underlines the importance of macrophages as modulators in skin regenerative processes, going beyond their primary function as phagocytic immune cells," say the authors in PLOS Biology.


Read more at: http://phys.org/news/2014-12-hair-growth-skin.html#jCp

 

[Fbalding84]

How about we could just fry our Androgen Receptors......That would solve it all

Specialized laser targeting them

 

[Swoop]

Activating hair growth with a little help from the skin


A group from the Spanish National Cancer Research Centre (CNIO) has discovered an unexpected connection—a link between the body's defense system and skin regeneration. It turns out that macrophages are involved. These are cells from the immune system that are in charge of devouring invading pathogens, a process called phagocytosis. The authors report that macrophages induce hair growth by surrounding and activating cells in the skin that have regenerative capacity, called stem cells. The discovery that macrophages activate skin stem cells could influence technologies with potential applications in tissue regeneration, aging, and cancer.
The authors of the study are Mirna Perez-Moreno and Donatello Castellana, from the Epithelial Cell Biology Group of the BBVA Foundation-CNIO Cancer Cell Biology Programme, along with Ralf Paus, a hair immunobiology expert from the University of Manchester and Münster. "We have discovered that macrophages, cells whose main function is traditionally attributed to fight infections and wound repair, are also involved in the activation of hair follicle stem cells in non-inflamed skin," says Perez-Moreno.
These findings emerged from an observation by Perez-Moreno while she was working on another research project. Intriguingly, the mice she was working with at that time started to regrow hair when they were given anti-inflammatory drugs. Curious as to whether close communication between stem cells and immune cells could explain this observation, the Perez-Moreno lab began to test different types of cells involved in the body's defense system for a role in hair growth. They observed that when skin cells are dormant, a fraction of macrophages die naturally due to a normal process called apoptosis. Surprisingly, the dying and surviving cells activated nearby stem cells and hair began to grow again.
Macrophages secrete a number of factors including a class of signaling molecules called Wnts. Importantly, when the researchers treated macrophages with a Wnt inhibitor drug, the activation of hair growth was delayed—demonstrating a role for Wnt from macrophages in promoting hair growth. Although this study was carried out in mice, the researchers believe their discovery "may facilitate the development of novel treatment strategies" for hair growth in humans.
The researchers used tiny droplets, or liposomes, to carry the drug used in the study. The future use of liposomes as a way to deliver a drug to specific cells is promising and may have additional implications for the study of several pathologies, says Donatello Castellana.
From a more fundamental perspective, this research is an effort to understand how modifying the environment that surrounds adult skin stem cells can regulate their regenerative capabilities. "One of the current challenges in the stem cell field is to regulate the activation of endogenous stem cell pools in adult tissues—to promote regeneration without the need of transplantation," says Perez-Moreno.
Because of this study, it is now known that macrophages play a key role in the environment surrounding stem cells. "Our study underlines the importance of macrophages as modulators in skin regenerative processes, going beyond their primary function as phagocytic immune cells," say the authors in PLOS Biology.


Read more at: http://phys.org/news/2014-12-hair-growth-skin.html#jCp

Thanks read that study, it's interesting indeed.

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Specialized laser targeting them

If only that was possible damn. Just zap those AR receptors from the dermal papilla cells = holy prevention cure.

 

[Python]

How about we could just fry our Androgen Receptors......That would solve it all

The problem with this is that we know it won't work if you're already reach a certain threshold. It has already been shown that even if someone gets castrated, they will not gain their hair back. So that shows that there is some crap water fall effect that goes beyond just androgenic sensitivity