Latest Patents From Dr. George Cotsarelis

[hellouser]

@Wolf Pack @Roberto_72 : Could he post some pics in the near future ? Thanks

It's a post from @BaldyBalderBald,
As he can't yet post some pics, I post for him the following Text


" Hi everyone,

First post here, just finally sign-up after few years lurking here for new upcoming treatments to get rid of fina after 13 years regimen of 1mg/d.
Started balding at 15....yeah 15 f*****g years, tried minoxidil until 18, then switched over fina cause minoxidil fucked up my scalp bad, managed to maintain Norwood 1.5 13 years but this f*****g disease finally seems to catch up with me...aaaanyways...been doin' some research on follicular neogenesis and i got some food for thoughts for you.

Creating some new hair follicles seems fine, but in order to achieve an acceptable cosmetic and natural look, it needs multiple criterias
1. Density, obviously
2. Thickening
3. Direction

I don't know if density and thickening results will be good, Follica and Dr. Cots seems to be ellusive on this part.
Third one seems to be the problem here, in all patents or discussions i've read about de novo HFs...well direction is not controlled by any means and to me this is the major issue of this technique, especially for hairline, no one wants a frontal hairline or hair randomly grow in every god damn directions, and most major Norwood 0 hairlines have a very specific direction pattern, like Christian Bale one for example :

View attachment 64575

f****r got a solid one.
Anyway the only sources i've find talking about this quote that de novo HFs directions are quite random and organised in clusters...in mice whatever.

View attachment 64576

"Distribution and orientation of neogenic hairs in regenerated wounds. (A) Commonly, regenerated HFs form one large cluster (also see Fig. 3). One or a few small secondary cluster(s) can also be present. (B) Seldom, multiple small de novo HF clusters can form (eight clusters here). (C), (D) Orientation of de novo HFs can range from seemingly random (D, purple region; also see Fig. 3) to unidirectional. Commonly, the neogenesis zone can contain several sub-clusters of HFs with distinct orientation (C). Hairs have similar direction within a sub-cluster, but often opposite of that in the neighboring sub-cluster (white vs. black in C and D). Here, WNT pathway reporter BAT-gal (A−C) and BRE-gal reporters (D) were used to aid visualization of neogenic hairs as strongly lacZ-positive. Size bar 1 mm."

Full paper here : http://onlinelibrary.wiley.com/doi/10.1002/reg2.38/full

Dr. Bernstein mention it too in an article talking about follicular neogenesis and hair cloning, quoting
"Another problem of hair cloning is that the orientation of hair direction must be controlled. With mouse experiments, the hairs grow at all different directions. Scientists need to find a way to align the hair so that it grows in the right direction. Hair, of course, must also be of a quality that is cosmetically acceptable and matches the patient existing hair. And the hair should grow in follicular units. Individual hairs will not give the fullness or natural look of follicular units."

Source : https://www.bernsteinmedical.com/medical-treatment/hair-cloning/answers/

Some photos of neogenesis or not quite good like this one, and you can see the direction randomness :
View attachment 64577
Noticed "graft" being mentionned, result of cultured DPCs cells being transplanted, same result as new formed DPCs cells.

@hellouser , if you're reading this, this got to be the first and major question for Follica's team at the next Hair Congress, but I already assume Dr. Cots will elude this again.

As for the DHT sensitivity of de novo HFs, I remember reading that they won't be but i can't find the source anymore, i'll keep searching, all I found is about PGD2 and seems to indicate the opposite actually, but i'll definetly retrieve the source where i've read they won't be sensitive, being basically "out of system" follicles.

Prostaglandin D2 Inhibits Wound-Induced Hair Follicle Neogenesis through the Receptor, Gpr44
http://www.sciencedirect.com/science/article/pii/S0022202X15361753 "

Just to be sure, the question should be

'Does Follica's method of wound induced follicle neogenesis take into consideration the direction of the new follicle and hair fibre that grows or will it take on the pattern of the previous hair before the balding state?'

If this is sufficient, I'll add this to my list as the first question. Perhaps Dr. Washenik could shed some light if not Dr. Cotsarelis.

 

[lemoncloak]

BTW does anyone know how follica is supposed to work? Like, do you need multiple visits for wounding or just once and then home application? If some molecules like fgf9 require wounding to penetrate the skin wouldn't you need many visits?
Alsocurious as to whether new hair can actually circumvent dht sensitivity as mentioned by BaldyBalderBald

 

[BaldyBalderBald]

Just to be sure, the question should be

'Does Follica's method of wound induced follicle neogenesis take into consideration the direction of the new follicle and hair fibre that grows or will it take on the pattern of the previous hair before the balding state?'

If this is sufficient, I'll add this to my list as the first question. Perhaps Dr. Washenik could shed some light if not Dr. Cotsarelis.

Yes, it's exactly my concern for this product

To add density it's seems good, but for the hairline...good question, disruption with compound seems to basically add DPC's everywhere, like you can add hair in the middle of your forehead ? Restoring the hairline seems difficult, even with top hair transplant docs

 

[BaldyBalderBald]

BTW does anyone know how follica is supposed to work? Like, do you need multiple visits for wounding or just once and then home application? If some molecules like fgf9 require wounding to penetrate the skin wouldn't you need many visits?
Alsocurious as to whether new hair can actually circumvent dht sensitivity as mentioned by BaldyBalderBald

Full protocol remains unknown, but making an educated guess, well, disruption is needed apparently, when skin is healed, compound alone can't generates new HFs so yeah, it seems that you'll need more than one visit depending of your current status and the wanted result i guess

As for dht sensitivity, still trying to find the source again, will post asap

 

[Roberto_72]

@Wolf Pack @Roberto_72 : Could he post some pics in the near future ? Thanks

It's a post from @BaldyBalderBald,
As he can't yet post some pics, I post for him the following Text


" Hi everyone,

First post here, just finally sign-up after few years lurking here for new upcoming treatments to get rid of fina after 13 years regimen of 1mg/d.
Started balding at 15....yeah 15 f*****g years, tried minoxidil until 18, then switched over fina cause minoxidil fucked up my scalp bad, managed to maintain Norwood 1.5 13 years but this f*****g disease finally seems to catch up with me...aaaanyways...been doin' some research on follicular neogenesis and i got some food for thoughts for you.

Creating some new hair follicles seems fine, but in order to achieve an acceptable cosmetic and natural look, it needs multiple criterias
1. Density, obviously
2. Thickening
3. Direction

I don't know if density and thickening results will be good, Follica and Dr. Cots seems to be ellusive on this part.
Third one seems to be the problem here, in all patents or discussions i've read about de novo HFs...well direction is not controlled by any means and to me this is the major issue of this technique, especially for hairline, no one wants a frontal hairline or hair randomly grow in every god damn directions, and most major Norwood 0 hairlines have a very specific direction pattern, like Christian Bale one for example :

View attachment 64575

f****r got a solid one.
Anyway the only sources i've find talking about this quote that de novo HFs directions are quite random and organised in clusters...in mice whatever.

View attachment 64576

"Distribution and orientation of neogenic hairs in regenerated wounds. (A) Commonly, regenerated HFs form one large cluster (also see Fig. 3). One or a few small secondary cluster(s) can also be present. (B) Seldom, multiple small de novo HF clusters can form (eight clusters here). (C), (D) Orientation of de novo HFs can range from seemingly random (D, purple region; also see Fig. 3) to unidirectional. Commonly, the neogenesis zone can contain several sub-clusters of HFs with distinct orientation (C). Hairs have similar direction within a sub-cluster, but often opposite of that in the neighboring sub-cluster (white vs. black in C and D). Here, WNT pathway reporter BAT-gal (A−C) and BRE-gal reporters (D) were used to aid visualization of neogenic hairs as strongly lacZ-positive. Size bar 1 mm."

Full paper here : http://onlinelibrary.wiley.com/doi/10.1002/reg2.38/full

Dr. Bernstein mention it too in an article talking about follicular neogenesis and hair cloning, quoting
"Another problem of hair cloning is that the orientation of hair direction must be controlled. With mouse experiments, the hairs grow at all different directions. Scientists need to find a way to align the hair so that it grows in the right direction. Hair, of course, must also be of a quality that is cosmetically acceptable and matches the patient existing hair. And the hair should grow in follicular units. Individual hairs will not give the fullness or natural look of follicular units."

Source : https://www.bernsteinmedical.com/medical-treatment/hair-cloning/answers/

Some photos of neogenesis or not quite good like this one, and you can see the direction randomness :
View attachment 64577
Noticed "graft" being mentionned, result of cultured DPCs cells being transplanted, same result as new formed DPCs cells.

@hellouser , if you're reading this, this got to be the first and major question for Follica's team at the next Hair Congress, but I already assume Dr. Cots will elude this again.

As for the DHT sensitivity of de novo HFs, I remember reading that they won't be but i can't find the source anymore, i'll keep searching, all I found is about PGD2 and seems to indicate the opposite actually, but i'll definetly retrieve the source where i've read they won't be sensitive, being basically "out of system" follicles.

Prostaglandin D2 Inhibits Wound-Induced Hair Follicle Neogenesis through the Receptor, Gpr44
http://www.sciencedirect.com/science/article/pii/S0022202X15361753 "

Thx @Noisette
I was frustrated cannot posting this

Great stuff.
Unfortunately there is some anti - spam rule that prevents new users to post links or pictures. I think it is ten posts minimum. Only Admin can tweak these forum rules.

 

[Noisette]

Just to be sure, the question should be

'Does Follica's method of wound induced follicle neogenesis take into consideration the direction of the new follicle and hair fibre that grows or will it take on the pattern of the previous hair before the balding state?'

If this is sufficient, I'll add this to my list as the first question. Perhaps Dr. Washenik could shed some light if not Dr. Cotsarelis.

Thank you Hellouser. it's well written

Great stuff.
Unfortunately there is some anti - spam rule that prevents new users to post links or pictures. I think it is ten posts minimum. Only Admin can tweak these forum rules.

Thanks Roberto ! @BaldyBalderBald : when you have 10 posts, you can post some links and pics.

 

[BaldyBalderBald]

Thank you Hellouser. it's well written



Thanks Roberto ! @BaldyBalderBald : when you have 10 posts, you can post some links and pics.

@hellouser @Roberto_72 @Noisette

Yeah, thank you all

9 messages, almost there, will try not saying bullshits till then !

 

[hellouser]

Thank you Hellouser. it's well written

Done, added to the list:

https://www.hairlosstalk.com/intera...user-to-kyoto-hair-congress-2017-fund.105184/

 

[BaldyBalderBald]

Apparently the mechanism that controls direction is called planar cell polarity and is still a subject of research. It guides the initial arrangement of cells. Not just hair, everything that forms a pattern. Here are some relative articles - the first one, with a quick read, doesn't say much besides a reference to PCP in flies https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257556/#!po=46.5517 the second is all about flies https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828277/#!po=56.9444 third is more general and perhaps more interesting http://jcb.rupress.org/content/207/2/171
Tbh the subject complexity to number of fucks given ratio is not looking very good for me. If anyone has the balls and will to look into PCP further be my guest. From what I'd read so far I thought perfect directionality is a given but it's nice to be reminded assumptions aren't always right.

Good find @lemoncloak, you're right on point with planar cell polarity. (PCP) -> not Phencyclidine, the hallucinogenic drug
This seems to be the issue in Wound‐induced hair follicle neogenesis (WIHN) :

"Hair orientation is another patterning feature that differs between normal skin and WIHN. During normal skin development, anterior−posterior polarity is in place at the early hair germ stage via planar cell polarity (PCP) dependent mechanisms.Interestingly, neogenic HFs in WIHN often share common orientation within a domain, and when domains are sufficiently large, cross‐like patterns reminiscent of those in mutants can arise in wild type wounds. Taken together, these correlations imply that WIHN fails to activate a global PCP‐dependent polarity mechanism. However, local PCP‐independent mechanisms may remain functional. Because the signaling nature of the PCP‐independent local hair reorientation process remains elusive, WIHN may prove to be a useful model for elucidating it."

Observed once again in mice, pictures posted by @Noisette in our collective post seems right on track, with a sub-cluster hair seems oriented the same way, but in a general global pattern, and therefore a large surface, PCP mechanism seems to fail. Hopefully, they will find a way, that's why trial are for I guess, and we don't know yet what's in the full treatment or wheter human hair responds the same.

More evidence that PGD2 inhibition is required for the protocol to work :
"Does hair neogenesis depend on the earlier, largely pro‐inflammatory signaling events that take place during the initial phase of wound closure? A recent study by Nelson et al. (2013) indicates a role for prostaglandin PGD2 signaling. Treatment of wounds with pro‐inflammatory PGD2 decreases the efficiency of hair neogenesis, while genetic deletion of the Gpr44 PGD2 receptor increases it. Future studies on the WIHN model will be necessary to decipher how pro‐ and anti‐inflammatory signaling pathways act to suppress and/or augment pro‐regenerative WNT signaling."

Follica protocol will definetly have a prostaglandin DP2 receptor antagonist like Fevi or Seti.

Full paper : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617665/

 

[dermrafok]

Good find @lemoncloak, you're right on point with planar cell polarity. (PCP) -> not Phencyclidine, the hallucinogenic drug
This seems to be the issue in Wound‐induced hair follicle neogenesis (WIHN) :

"Hair orientation is another patterning feature that differs between normal skin and WIHN. During normal skin development, anterior−posterior polarity is in place at the early hair germ stage via planar cell polarity (PCP) dependent mechanisms.Interestingly, neogenic HFs in WIHN often share common orientation within a domain, and when domains are sufficiently large, cross‐like patterns reminiscent of those in mutants can arise in wild type wounds. Taken together, these correlations imply that WIHN fails to activate a global PCP‐dependent polarity mechanism. However, local PCP‐independent mechanisms may remain functional. Because the signaling nature of the PCP‐independent local hair reorientation process remains elusive, WIHN may prove to be a useful model for elucidating it."

Observed once again in mice, pictures posted by @Noisette in our collective post seems right on track, with a sub-cluster hair seems oriented the same way, but in a general global pattern, and therefore a large surface, PCP mechanism seems to fail. Hopefully, they will find a way, that's why trial are for I guess, and we don't know yet what's in the full treatment or wheter human hair responds the same.

More evidence that PGD2 inhibition is required for the protocol to work :
"Does hair neogenesis depend on the earlier, largely pro‐inflammatory signaling events that take place during the initial phase of wound closure? A recent study by Nelson et al. (2013) indicates a role for prostaglandin PGD2 signaling. Treatment of wounds with pro‐inflammatory PGD2 decreases the efficiency of hair neogenesis, while genetic deletion of the Gpr44 PGD2 receptor increases it. Future studies on the WIHN model will be necessary to decipher how pro‐ and anti‐inflammatory signaling pathways act to suppress and/or augment pro‐regenerative WNT signaling."

Follica protocol will definetly have a prostaglandin DP2 receptor antagonist like Fevi or Seti.

Full paper : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617665/

Good Find! @BaldyBalderBald

https://www.ncbi.nlm.nih.gov/pubmed/28941500

Prostaglandin D2 Uses Components of ROS Signaling to Enhance Testosterone Production in Keratinocytes.

 

[BaldyBalderBald]

Good Find! @BaldyBalderBald

https://www.ncbi.nlm.nih.gov/pubmed/28941500

Prostaglandin D2 Uses Components of ROS Signaling to Enhance Testosterone Production in Keratinocytes.

Yes @dermrafok , nice one ,again this damn PGD2 ! I rather fighting this f***er rather than lowering DHT imo.
Conclusion is nice.
"Thus, we propose that Androgenetic Alopecia patients might benefit from the use of N-acetyl-cysteine or other antioxidants as a supplement to currently available or emerging Androgenetic Alopecia therapies such as finasteride, minoxidil, and PGD2 receptor blockers."

Seems nutrionnal supplement are useful after all, as a complementary treatment. Referring finasteride and minoxidil as "emerging" treatments tho...what is this ? 1980's ?
This paper refers to Nutritional and antioxidant therapy too, such as Biotin, Zinc, and Omega 3 fatty acids

https://www.omicsonline.org/open-ac...air-transplantation-jctt1000105.php?aid=68395

 

[Mazaza]

Yes @dermrafok , nice one ,again this damn PGD2 ! I rather fighting this f***er rather than lowering DHT imo.
Conclusion is nice.
"Thus, we propose that Androgenetic Alopecia patients might benefit from the use of N-acetyl-cysteine or other antioxidants as a supplement to currently available or emerging Androgenetic Alopecia therapies such as finasteride, minoxidil, and PGD2 receptor blockers."

Seems nutrionnal supplement are useful after all, as a complementary treatment. Referring finasteride and minoxidil as "emerging" treatments tho...what is this ? 1980's ?
This paper refers to Nutritional and antioxidant therapy too, such as Biotin, Zinc, and Omega 3 fatty acids

omicsonline.org/...

If I were you I would be careful with anything that is published in any journal of the 'omics group'. They are well known in the biomedical scientific community for being what is called a 'predatory publisher', meaning they they:
* send spam to get people to submit articles in their journals (and pay fees),
* publish articles of very low scientific quality
* basically accepts every publication without any serious peer reviewing


Relevant website on that subject: beallslist . weebly . com

Also, it is not because a researcher publishes one or few articles in such a journal that it is a bad researcher. It becomes 'smelly' when a researcher publishes ONLY in predatory journals and/or is in the editorial board.

 

[dermrafok]

Yes @dermrafok , nice one ,again this damn PGD2 ! I rather fighting this f***er rather than lowering DHT imo.
Conclusion is nice.
"Thus, we propose that Androgenetic Alopecia patients might benefit from the use of N-acetyl-cysteine or other antioxidants as a supplement to currently available or emerging Androgenetic Alopecia therapies such as finasteride, minoxidil, and PGD2 receptor blockers."

Seems nutrionnal supplement are useful after all, as a complementary treatment. Referring finasteride and minoxidil as "emerging" treatments tho...what is this ? 1980's ?
This paper refers to Nutritional and antioxidant therapy too, such as Biotin, Zinc, and Omega 3 fatty acids

https://www.omicsonline.org/open-ac...air-transplantation-jctt1000105.php?aid=68395

Thus, we propose that Androgenetic Alopecia patients benefit from the use of N-acetyl-cysteine or other antioxidants as a supplement to currently available or emerging Androgenetic Alopecia therapies such as finasteride, minoxidil, and PGD2 receptor blockers. It seems like Chan,J et al are sure that a new treatment for male pattern baldness is: PGD2 receptor blockers. As the ancient (80's treatments Minoxidil and Finasteride...)

 

[BaldyBalderBald]

yeah, will be more careful then

 

[d3nt3dsh0v3l]

Just to be sure, the question should be

'Does Follica's method of wound induced follicle neogenesis take into consideration the direction of the new follicle and hair fibre that grows or will it take on the pattern of the previous hair before the balding state?'

If this is sufficient, I'll add this to my list as the first question. Perhaps Dr. Washenik could shed some light if not Dr. Cotsarelis.

Hey hellouser. If you don't mind, can you also ask more generally how Follica affects the AP muscle? When we bald, it degrades, right? Do the new follicles link up to the old AP? Do they regenerate their own AP? Is the old AP rejuvinated? Do the new follicles not need an AP? As far as I know, the AP sets the hair direction, or at the very least, the AP and native hair share the same alignment. Of course the AP is an integral part of the FU health so that's why I am concerned about it.

Are the new follicular units producing up to 4 hairs? Or is it just the primary hair?

 

[joni106]

Hello everyone,
I will thank those who can answer a few questions about microneedling.
I use Dreamaroller 1.5 every two weeks. 48 hours after roll I put minoxidil 10% and continues to use minoxidil every night until the next roll.
I I use mix essential oils with castor oil, emo oil and coconut 5 times at week
I also take every day vitamin c, gellatin, msm, saw palmmeto, biotin.

please i wanted to ask if i could take the supplements day after the microneedling or wait a few days, and also for the mix oils - to wait a few days or can be used the day after?

Sorry for my English ... and thanks in advance!

 

[hellouser]

Hey hellouser. If you don't mind, can you also ask more generally how Follica affects the AP muscle? When we bald, it degrades, right? Do the new follicles link up to the old AP? Do they regenerate their own AP? Is the old AP rejuvinated? Do the new follicles not need an AP? As far as I know, the AP sets the hair direction, or at the very least, the AP and native hair share the same alignment. Of course the AP is an integral part of the FU health so that's why I am concerned about it.

Are the new follicular units producing up to 4 hairs? Or is it just the primary hair?

Can you guys post your questions in the official thread? I can't keep up with questions all over the place.

Here: https://www.hairlosstalk.com/intera...user-to-kyoto-hair-congress-2017-fund.105184/

 

[InBeforeTheCure]

Apparently the mechanism that controls direction is called planar cell polarity and is still a subject of research. It guides the initial arrangement of cells. Not just hair, everything that forms a pattern. Here are some relative articles - the first one, with a quick read, doesn't say much besides a reference to PCP in flies https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257556/#!po=46.5517 the second is all about flies https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828277/#!po=56.9444 third is more general and perhaps more interesting http://jcb.rupress.org/content/207/2/171
Tbh the subject complexity to number of fucks given ratio is not looking very good for me. If anyone has the balls and will to look into PCP further be my guest. From what I'd read so far I thought perfect directionality is a given but it's nice to be reminded assumptions aren't always right.

Devenport and Fuchs say:

Interestingly, once epidermal PCP was fully established in vivo, it was maintained in vitro. However in vivo, when skins from embryos E17.5 or younger were rotated 180 degrees and grafted onto adult hosts, HFs across the graft reoriented anteriorly towards the host body axis (Supplementary Fig. S2). Thus once established, PCP can continue to respond to directional cues.

So something doesn't go right during WIHN?

 

[Medina]

I don't think direction will be a problem, again I go back to my wrist injury...the hairs follow the same direction and have the same attributes to the nearest hairs around them (my arm hair)

And they sort of "join up" with them too, making it look like a pattern and not a random blob of follicles

 

[Leto]

I don't think direction will be a problem, again I go back to my wrist injury...the hairs follow the same direction and have the same attributes to the nearest hairs around them (my arm hair)

And they sort of "join up" with them too, making it look like a pattern and not a random blob of follicles

Also when you remember "barbecue head" guy - he fall into fire with front part of head, hairline part. And his hariline, density looks rather okay. Pictures aren't sharp, but you can see it.