Understanding and modelling the hairloss process

[bushbush]

can the genes that cause male pattern baldness be deactivated or removed?

Theoretically, ANY gene in your body can be SILENCED using a technique known as RNAi. https://en.wikipedia.org/wiki/RNA_interference However, it is not yet extensively tested in mammals, cost prohibitive, and would require frequent application. It may never be practical for this purpose.

 

[Helios]

Can it be that it can be hormone related, and i don't mean DHT, but i've been thinking more in the direction of estrogen deficiency in males.

 

[brunobald]

Benjt I love your work on this, bringing together of data like this. I started something similer to map out ideas for Hellouser dermarolling trial. Its here on Mind42.com

http://mind42.com/public/831fd9a5-7dff-474d-8e05-cca45a37b0b3

This is just a prototype, the nice thing about online mind maps like this is collaborations. I can add people to a list who then have access to mod the map just like wikipedia. You can also link mind maps together so you could have one overall casues and cures for Androgenetic Alopecia mind map then have subsections for more specific ideas. It has the potential to get messy, but the benefits of having 100's of people constantly refining something like this speed and shear depth of info.

 

[benjt]

BAM. Exactly what I was talking about:
"Results: Wnt3a-dependent keratinocyte growth was suppressed by the addition of dihydrotestosterone (DHT) in coculture with DP cells that were derived from Androgenetic Alopecia patients, but growth was not suppressed in coculture with DP cells from non-Androgenetic Alopecia males."
Source: http://mend.endojournals.org/content/23/2/279.full

That completely proves that DHT is not the culprit or cause, but only the trigger. High DHT values in non-Androgenetic Alopecia affected people doesn't do anything, showing that DHT does not inhibit growth per se. It is only the (probably immune) reaction in Androgenetic Alopecia patients that takes the DHT as a reason to cause inflammation around follicles in the scalp.

 

[The12thMan]

benjt,

Great work! I have little to add on a scientific basis, but here are a few randoms thoughts.

1) My pet theory is that ALL BALDNESS subtypes are auto-immune disease responses. As such, could one of the treatments be immunotherapy with the causative triggers?
2) I have severe seasonal allergies (mold) and oddly enough my male pattern baldness kicked in after my first year of immunotherapy.
3) I believe DHT is one of the factors, but not the smoking gun it has been believed to be. This explains to me, why there are varying degrees of efficacy with Propecia.
4) Once the factors are identified, I believe treating and reversing baldness will be extremely easy. I have no scientific basis for this, just pure optimism!

Keep up the good work!

 

[marku]

^ castrate a man who is balding and they will stop. Propecia's varying success is due to decline in effectiveness over time, or the bodies ability to counteract androgen deprivation. When there are no androgens though, there is no hair loss. Propecia only puts a dent into our androgen supply.

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My point is, If you have Androgenetic Alopecia, DHT will progress your balding, no matter who you are. Yes there are other variables at play, but DHT is one of the constant ones

 

[Sparky4444]

^ castrate a man who is balding and they will stop. Propecia's varying success is due to decline in effectiveness over time, or the bodies ability to counteract androgen deprivation. When there are no androgens though, there is no hair loss. Propecia only puts a dent into our androgen supply.

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My point is, If you have Androgenetic Alopecia, DHT will progress your balding, no matter who you are. Yes there are other variables at play, but DHT is one of the constant ones

Dude -- you are making a LOT of statements here without really anything to back them up...caution...

 

[marku]

Benjt where would a proteaseome inhibitor fall into place on this chart?

http://www.ncbi.nlm.nih.gov/pubmed/23963711

 

[benjt]

1) My pet theory is that ALL BALDNESS subtypes are auto-immune disease responses.

I agree.

As such, could one of the treatments be immunotherapy with the causative triggers?

The problem is: Yes, it could, but nobody has looked into this and we lack the facilities to do that ourselves.

2) I have severe seasonal allergies (mold) and oddly enough my male pattern baldness kicked in after my first year of immunotherapy.

In this case, I'd say coincidence. Let me guess, immunotherapy between 17 and 21?

3) I believe DHT is one of the factors, but not the smoking gun it has been believed to be. This explains to me, why there are varying degrees of efficacy with Propecia.

As I stated a couple of times, DHT is not the cuplrit, but only the trigger. DHT by itself is not harmful, as proven by studies where hair follicles from people not suffering from Androgenetic Alopecia were exposed to high DHT concentrations, but nothing happened. In contrast, follicles from people with Androgenetic Alopecia reacted to DHT. Thus, it DHT cannot be the cuplrit per se, it is a wrongful reaction of our bodies.

4) Once the factors are identified, I believe treating and reversing baldness will be extremely easy. I have no scientific basis for this, just pure optimism!

Don't wanna curb it, but unfortunately there are a few things which - in my opinion - make regrowth very difficult:
a) fibrosis of bald areas, which makes it very hard for follicles to do their job, and even if they manage to produce new hair, the hair has a tough time getting to the surface, thus clogging the follicle
b) destruction of brown adipose tissue in bald areas, depriving follicles of nutrients and platelets
c) Even though Follica apparently succeeds to perform follicle neogenesis now, a) and b) as problems still persist

@marku: I don't know if it applies to our case at all. The way this works is similar to one of the interpretations of minoxidil (minoxidil extending the anagen phase). The problem is: Even when the anagen phase is extended, the follicle will take damage from the male pattern baldness process nonetheless. It will produce (and keep) hair longer, but eventually will fail to produce any new hair due to miniaturization of the follicle, which will occur nonetheless. If my understanding is correct, this will not make balding actually slow down (e.g., divide the "balding speed" by a certain factor, slowing down the whole process), but only delay it by a constant factor. This is only speculation though, but makes sense, since this only seems to extend the anagen phase, but does nothing to preserve the follicle itself.

 

[persistentone]

Don't wanna curb it, but unfortunately there are a few things which - in my opinion - make regrowth very difficult:
a) fibrosis of bald areas, which makes it very hard for follicles to do their job, and even if they manage to produce new hair, the hair has a tough time getting to the surface, thus clogging the follicle
b) destruction of brown adipose tissue in bald areas, depriving follicles of nutrients and platelets

But in your own case - based on photos you supplied - didn't you go from nearly totally bald to having quite substantial amounts of hair? Whatever level of fibrosis you had didn't seem to stop hair growth.

 

[benjt]

The only photo I supplied so far is one documenting the wrinkles I got from minoxidil. I did not upload any of my hair state. You must be mistaking me for someone else.

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And I updated the graph again.

Changelog:
- added FGF-9 and beta-catenin next to the derma rolling and wounding
- added edge from PGE-2 to FGF-9 (though I am not entirely sure about this...)
- added brown adipose tissue and related nodes
- removed animal proteins, as their impact seems to be close to zero, and thus even less than the other diet components listed there
- reorganized some nodes cause things were getting too messy

Now updated to Version 1.4. Click for full resolution:

 

[marku]

Thanks benjt! U are simply amazing. Do u have a link to the study that shows dermarolling improves collagen acclamation?
Because I thought dermarolling builds collagen, which would be bad no?
Cheers

 

[benjt]

The problem is that in bald areas, there is thick, hard fibrotic collagen (caused by local immune reaction and inflammation). This collagen is destroyed by the dermaroller, and then replaced by the body with normal, soft, non-fibrotic collagen. Only as baldness progresses, the scalp collagen becomes fibrotic.

 

[persistentone]

The problem is that in bald areas, there is thick, hard fibrotic collagen (caused by local immune reaction and inflammation). This collagen is destroyed by the dermaroller, and then replaced by the body with normal, soft, non-fibrotic collagen. Only as baldness progresses, the scalp collagen becomes fibrotic.

I had confused you with casperz, sorry.

His progress - with photos - is here:

http://www.hairlosstalk.com/interact/showthread.php/35120-Success-on-KSR-with-pics

He makes unbelievable progress from near total scalp baldness to reasonably thick full head of hair.

What's very strange is he backed off the regimen he follows and started to regress, but he never controlled the variables carefully enough to know which missing treatment was causing the new hairloss. It's kind of a waste of a great experiment to simply give up like he did.

 

[marku]

Hey benjt, i have some questions... Can you link me to the study that shows tgf-b and caspase simply stop follicle production without any in between stage? I'm trying to decide if tgf b is worth treating or if it doesn't really affect the "attack" of a hair follicle. Where is the science for fenugreek? If u have time, Can you post the studies you references for each part of this chart? I'd like to help and offer my thoughts as well.

 

[Koga]

Is it possible the green and red arrows aren't always used 'correctly'? Or what is the exact meaning of the colors? I guessed green = influences; red = doesn't influence. Great scheme though, reaaaally great. If you would want to make this an internet hit, you should at the studies in footnotes. But even so, great work. Thanks a lot!

 

[karankaran]

SOY LOWERS IGF - 1 , that is WRONG INFO...btw i appreciate all the effort that went into making that chart, it is really illuminating... and yes i have allergy conditions too... a lot of stuff is connected here!!!

 

[darwin101]

I have allergies to cats and dust.. not sure about pollen.

I'm going to keep an eye out for sneezing chrome domes from now on.

 

[odalbak]

VERY useful. Thanks for your work, Benjt.

 

[benjt]

I will make another update to this graph in 2 to 3 weeks time. I learned a great deal from some studies posted in the dermarolling monument thread, mostly in regards to natural hair cycling using PGD2, which resulted in some reasonable theories about male pattern baldness hairloss. But I still gotta confirm this stuff. It's not big (mostly about PGD2 overspilling, thus explaining the regular, non-diffuse pattern where only the direct neighborhood is affected) and the fibrosis crushing follicles. In the latter case, someone (I think squeegee) posted some "nice" (well, they are enlightening, but for us it looks rather bad) cross sections of crushed follicles.

@Axwell: You can't receive PMs for some reason, thus I will post my reply to your PM here:
I was given this proposal [of collaboration] once or twice before already. However, I am keeping it as non-collaborative work on purpose currently. I opened a thread for my graph both here and on hairlosshelp, and the suggestions I got are sometimes rather uninformed, based on personal beliefs, or based on stuff people read on forums.
I created the graph exclusively using research articles, which many people have no access to. I'm not claiming it is the whole truth - hell, even though it's quite complex it's definitely only a part of it and I know that I'm still missing out on a lot, mostly in the "natural PGD2 signaling for hair cycling and possible overspill PGD2 due to androgenic overexpression in "waves" " department, but at least I can ensure right now that it is 100% correct. Or at least 100% correct based on my sources, which might be wrong, but it's the best shot we got. I will post an update of it in approx. 2 weeks, when I got the whole situation with natural hair cycling in response to PGD2, which are upregulated by androgens, occuring in waves in the "neighborhood" figured out.

If you want, you can put up a copy on draw.io, I don't mind. But I wanna make sure that the copy I "maintain" is 100% confirmed and based on research articles. And if you got anything to add to my copy, it's more than appreciated