Over the past few years, I have discussed the janus kinase signal transducer and activator of transcription (JAK-STAT) signaling pathway a number of times.  It has become of increasing importance in the hair loss world ever since JAK inhibitors were first shown to cure alopecia areata (AA) in 2014.  Even prior to that development, there had always been some interest in the JAK-STAT signaling pathway and its relationship to the hair follicle cycle.

However, since 2014, research in this area seems to have multiplied significantly.  In 2015, I discussed Dr. Angela Christiano, Dr. Claire Higgins et al’s groundbreaking paper titled “Pharmacologic inhibition of JAK-STAT signaling promotes hair growth“.

Now, in the latest (November 2016) issue of Journal of Investigative Dermatology, Columbia University’s Dr. Angela Christiano, Dr. Etienne Wang and Dr. Sivan Harel have published a new paper titled “JAK-STAT signaling jump starts the hair cycle“.  Thanks to the commentator in the last post who notified us about this.

However, it should be noted that this paper does not pertain to any new study or research by Dr. Christiano!  Instead, it is largely an analysis by the Columbia University team of a study/paper that was published earlier this year by Dr. Julien Legrand and his team at The University of Queensland.  This study from Australia was titled “STAT5 activation in the dermal papilla Is important for hair follicle growth phase Induction“.  The conclusion of that paper was that “STAT5 activation acts as a mesenchymal switch to trigger natural anagen entry in postdevelopmental hair follicle cycling“.  STAT5 is an acronym for signal transducer and activator of transcription 5.

Dr. Christiano’s team raises some interesting points in their analysis, especially the fact that while Dr. Legrand’s research has shown that JAK/STAT5 signaling in the dermal papilla is required for anagen onset in the murine (mice) hair cycle, other researchers have shown that JAK inhibition is able to induce the transition of telogen to anagen in wild-type mice.  This contradiction highlights the complexity  and still yet to be fully understood nature of JAK-STAT signaling in the various stem cell niches of the hair follicle.

Dr. Christiano continues to believe that topical JAK inhibitors could work to treat regular male pattern hair loss via the following quotes:

“Targeting the JAK-STAT pathway might be a potential treatment for nonimmune alopecias”.

“Further work in this exciting area may uncover novel pathways that control hair follicle stem cell quiescence and activation.  Targeting
these pathways pharmacologically may facilitate the discovery of new therapies to treat various forms of alopecia”.

“In our recent study (Note: its the one I mentioned earlier from 2015) we found that in wild-type mice, topical application (rather than systemic treatment) with JAK inhibitors was required to trigger the telogen-to-anagen transition, possibly due to a requirement for high threshold local concentrations of the drug in the hair follicle.  Further, we found that the timing of topical treatment was crucial: treatment induced hair growth only if administered after 8.5 weeks, during late telogen“.

Nothing groundbreaking in this development, but it seems like the University of Queensland based Australian team of researchers is important enough to warrant inclusion in my global map of hair loss research centers.  One of the co-authors (Dr. Kiarash Khosrotehrani) of their paper specifically mentions research interest in “hair follicle biology, cycling and regeneration” in his biography page.

FYI:  For the scientists amongst you that are interested, there is another paper in this same November 2016 issue of Journal of Investigative Dermatology titled: “Effects of Imiquimod on Hair Follicle Stem Cells and Hair Cycle Progression.”

I have mentioned platelet-rich plasma (PRP) in a dozen or so posts on this blog in the past three years, albeit some of those mentions were a small part of much larger posts.  Although the positive effect of PRP on hair is somewhat controversial (although an increasing number of PRP and hair related studies from around the world are supportive), there is no controversy when it comes to the fact that PRP contains numerous concentrated growth factors that can benefit hair.

While in the past I have briefly discussed some of the key growth factors that are highly concentrated in PRP, I think that it is worth having a separate post here that discusses all of them in a bit more detail.  It took me a while to research and write this post, and there is a good chance that I am still missing things so any corrections and suggestions in the comments are most welcome.

It should be noted that even many non-PRP related hair loss research papers and hair loss products have targeted one or more of the below listed growth factors for analysis or in order to stimulate hair growth. There is a good chance that both PRP as well as hair loss products that contain some or all of the below growth factors make existing hair stronger, but it is highly unlikely that they ever bring back hair that has been lost for a long time in my opinion. They could bring back recently lost hair, but that is also a controversial subject.

Growth Factors in Platelet-Rich Plasma

The key growth factors in PRP that are supposedly beneficial to hair growth are:

• Insulin-Like Growth Factor 1 (IGF-1).
• Fibroblast Growth Factor (FGF).
• Platelet-Derived Growth Factor (PDGF).
• Vascular Endothelial Growth Factor (VEGF).
• Epidermal Growth Factor (EGF).
• Transforming Growth Factor Beta (TGF-β).
• Nerve Growth Factor (NGF).

IGF-1

I start with the growth hormone insulin-like growth factor 1 (IGF-1) because I have already covered it a few times on this blog before.

• Promotion of IGF-1 expression is one of the main considerations behind Shiseido’s bestselling adenosine based products.
• US-based Follicept is also targeting IGF-1 delivery in its hair loss product.
• Adipose-derived stem cells (ADSCs — one of the more exciting recent developments in the hair loss world) are rich in various growth factors including IGF-1.
• Last year, an important and widely publicized study found that topical application of oleuropein (derived from the leaves of olive drupes) induces hair growth in mice.  According to the study findings, oleuropein-treated mouse skin showed substantial upregulation of IGF-1.

FGF

I list fibroblast growth factor (FGF) next because I have also covered it many times on this blog before. There are 22 types of FGFs numbered FGF-1 through FGF-22. A significant number of these influence hair growth and I may write an entire detailed post on FGFs at some point in the future.  I have covered some of the key ones on this blog before, in particular FGF-5, which discourages hair growth and has to be inhibited. Australian company Cellmid’s Evolis line of products claims to inhibit FGF-5.

Note that PRP does not inhibit growth factors, so it is more relevant for the purposes of this post to discuss some of the FGFs that promote hair growth.  It seems like the main ones are FGF-1, FGF-2, FGF-7, FGF-9 and FGF-10.  Evidence for three of those (FGF-1, FGF-2 and FGF-10) positive effects on hair is found in an important 2014 study from China. Note that “hair cell regeneration” or variations of that term are mentioned a number of times in this study, even if in mice.  PRP is said to increase FGF-2 concentration levels. Interestingly, when I interviewed Dr. Malcolm Xing last year, he mentioned that FGF-2 is the preferred growth factor used at this clinic for his work purposes.

FGF-9 has become an especially important growth factor in large part due to the work of the renowned Dr. George Cotsarelis, who holds a patent titled “Fibroblast growth factor-9 promotes hair follicle regeneration after wounding“.  Dr. Cotsarelis is also a co-author of a 2013 paper that concludes: “The importance of FGF-9 in hair follicle regeneration suggests that it could be used therapeutically in humans“.

Finally, FGF-7 (also called keratinocyte growth factor, or KGF) is required for hair growth.  The well known researcher Dr. Elaine Fuchs co-authored an important study on FGF-7, hair development and wound healing all the way back in 1995.

PDGF

Platelet-derived growth factor (PDGF) is a key growth factor involved in blood vessel formation.  A 2006 study from Japan found that “PDGF isoforms induce and maintain anagen phase of murine hair follicles“. Adipose-derived stem cells (ADSCs) are rich in various growth factors including  PDGF, and are becoming increasingly utilized in the hair loss world.

VEGF

Vascular endothelial growth factor (VEGF) is also involved in blood vessel formation.  A 2001 study concluded that “normal hair growth and size are dependent on VEGF-induced perifollicular angiogenesis”.  Note that Shiseido’s adenosine based shampoo also promotes the expression of VEGF.  The previously discussed adipose-derived stem cells are rich in various growth factors including  VEGF.

EGF

Epidermal growth factor (EGF) promotes cell growth, proliferation and differentiation.  A 2003 study from Hong Kong concluded that EGF functions as a biological switch that is “turned on and off in hair follicles at the beginning and end of the anagen phase of the hair cycle“.

TGF-β

Transforming growth factor beta (TGF-β) is a cytokine protein growth factor.  From the brief research I did, it seems like TGF-β actually adversely impacts hair growth!  e.g., see here, here and here. So I am not sure if this growth factor in PRP benefits hair.  Will update this if I find out more.

NGF

There seem to be mixed opinions on the impact of nerve growth factor (NGF) on the hair cycle in any significant manner.  A 2006 study suggests both anagen-promoting and catagen-promoting effects of NGF on the hair cycle. Another study, also from 2006, seems to also find different effects of NGF on the hair cycle.

•  The new HairSite forum.

HairSite Forum History

When I first started reading about hair loss online around 15 years ago, my favorite place to visit was probably www.hairsite.com.  At the time, it had an excellent and very active hair loss forum. Unfortunately, this has not at all been true during the past several years — see link to the old retired-as-of-today HairSite forum.  The domain name hairsite.com was first registered on February 24, 2017, almost 20 (!) years ago and I am pretty sure that the owner has always been the current owner David Tse.

The most surprising thing about HairSite was that of all the numerous English language hair loss forums out there, the hairsite.com forum had by far the most unique and slightly convoluted layout.  For most new visitors, it was often very frustrating to navigate this layout.  The threads could be viewed via “board view” or via “thread view” if you were able to notice that (I think it took me months of visiting before I even saw those options and realized what they meant).  Adding to the confusion, it was often not clear how the HairSite forum software decided on when to move a new thread that you might have initiated to the top of a forum category versus keeping it lower down the page and less visible to visitors. On top of all this, there were 100s of valuable pages within hairsite.com as well as within the affiliated hairsite4.com that you had no easy way to access and could just stumble upon by accident or when David linked to them in the forums.

Over the years, a number of people complained about the HairSite forum and website layout, but the owner David stuck to his guns and never revamped the forum.  He did make some tweaks (e.g., this one in 2007), but he kept the overall unique layout and appearance of the threads and comments as is.

Some of the most prolific and interesting (often crazy — e.g.,  a guy name “Common Sense” comes to mind) forum posters on HairSite were for whatever reason very attracted to its layout and never posted on any other “normal” hair loss forums.  HairSite was the first forum to have a very active hair multiplication section and perhaps that was a big part of its charm. I liked the fact that the HairSite forum was the simplest forum out there and had few categories (what some also call “sub-forums” or “subsections”). Most hair loss forums out there seem to have at least 20 categories.  Even in recent times, some posters have decided to post their very unique stories solely on HairSite, despite the fact that the forum has become much less active than most other English language hair loss forums out there.  For example, last year I was lucky to stumble upon Christopher1’s experiment with a topical JAK inhibitor for AGA as well as his Kerastem treatment testimonial when considering the fact that I was rarely visiting HairSite at the time.

David has in general been very hands-off in terms of the links that he allows on HairSite and he rarely censors discussions.  Most forum owners are not so open minded.  Even worse, some limit hair transplant related discussions to only advertising surgeons, which is a shame.  e.g., if someone asks “who is the best hair transplant surgeon in county XYZ?”, people should be allowed to discuss any of the options out there, but some forums only allow discussion of advertising surgeons.  I have not checked recently, but I presume that David still allows discussion of all hair transplant surgeons, whether advertisers or not.

Some of the Greatest Hits from the Past

Over the years, HairSite was without a doubt the best place in the world when it came to discussions about Dutasteride (brand name Avodart) and Dr. Coen Gho.  Both subjects are among the 10 most discussed  topics in the hair loss world during the past 15 years, with only the former justifiably so. HairSite was also one of the best places out there when it came to the initial years of discussion related to Aderans, Histogen and Intercytex.  In more recent years, HairSite has become the best place to read about the world’s three most experienced (in my opinion) follicular unit extraction (FUE) and body hair transplant (BHT) hair transplant practitioners in Dr. John Cole, Dr. Arvind Poswal and Dr. Ray Woods. All three of these esteemed surgeons participate on the HairSite hair transplant forum section and often make very though provoking comments, with the latter two sometimes getting into entertaining soap opera type arguments with each other.

Many of the old HairSite forum comments and threads were often very interesting or comedic, (especially in the hair multiplication and hair transplant sections) and it is too bad that I never saved my favorites (although a huge number of old links seems to be nonexistent today anyway). However, my favorite parts about HairSite entailed David’s extremely detailed and useful surveys and statistical summaries.  David put in a huge solo effort in these compilations.  I have linked to a few of these on this blog before. Below, I list some of my favorite efforts from David that are worth reading and I will update this list if I decide to spend more time on searching the archives (I couldn’t find many that I remembered, and I think most of those were in entirely blue color pages that seem to be gone now):

• The hair transplant patient summaries by surgeon is exceptional work, even though it only covers advertising surgeons who post before and after photos on HairSite.  After clicking on “Details” next to a surgeon name, make sure to go to the top right of the new page to see all the results (e.g., Dr. Poswal has 10 pages of results).
• Over the years HairSite had a number of excellent pages on Dutasteride (brand name Avodart) user surveys, but this is the best one that I could find for now from the archives that are still visible.
• Interview with Dr. Monahan during a time when numerous people thought that Avodart was the cure for hair loss and were obsessed with this man.

HairSite Forum Finally gets a Real Upgrade, but Thankfully Remains an Outlier

Earlier this year, David announced that the HairSite forums and website were both getting upgraded.  I was extremely pleased to hear that as I did not want HairSite to go extinct and felt like that was slowly happening to all the forum categories on there other than the hair transplant one.  After some delays and hiccups, yesterday the new HairSite forum finally went live and what a nice surprise to see the final result.  I encourage blog readers to join that forum if you have not done so already.

True to form, David has once again created the most unique and unusual hair loss forum out there (and the most simple one yet again).  This time he has combined all main forum categories into the same page, with the “category” column indicating the subject matter (Note: I am using a desktop.  Mobile view is very different). There is a selection menu on the upper left from where you can pick a category so as to only see threads for that particular subject matter if you so desire.  You can sort the viewing order by clicking on some of the columns (both ascending and descending options available), but the default sort by the “Activity” column from most recent to oldest is probably best most of the time.

I love the “User” column icons with forum member first name initials, that are like what you see nowadays in phone text messaging apps.  In this case, you can even hover over the icons to see who started the thread, who is/are the most frequent poster(s) in the thread, and who made the last comment in the thread. Very useful and succinctly presented.

Follica RAIN

Who else but commentator “Mike” to make us aware of the latest news about Follica? I am a bit annoyed that my google hair related alerts never give me the Follica information that Mike gives me. Whatever happened to artificial intelligence taking over? Joking aside, in the last post Mike made a comment that during PureTech (Follica majority owner)’s latest investor forum webcast, they had a slide in which they named Follica’s androgenetic alopecia product as “RAIN“. The slide is 105-106  minutes into the presentation. I was surprised at such an acronym.

I would have assumed they any acronym for a Follica product would definitely include a “W” for “wounding” or an “SD” for “skin disruption” in there. What could RAIN mean? From browsing Follica’s website, I would guess that the “R” might stand for “regeneration” and the “N” might stand for “neogenesis”. Of course there are numerous possible relevant words that one can come up with for these letters and I am curious what readers think. Thankfully, there is no “M” in the acronym as that would have resulted in much more discussion yet again about the compound that Follica will be using being solely or largely based upon “Minoxidil”, which is highly unlikely. And no, I do not thing that the “R” stands for brand name Minoxidil product “Rogaine”!

Confirmation of First Half 2017 Pivotal Study Initiation

In the above webcast, Follica confirmed (this slide is also in the 105-106 minute section) that its delayed pivotal study would be initiated during the first half of 2017. In an earlier post from April this year, I mentioned Follica’s plans to start this study in the second half of 2016 with a best case product release date of 2018. A few months ago they then announced the delay of the pivotal study into 2017 and this is now confirmed. I would guess that the above best case product release scenario date must have now shifted to 2019?

It should also be noted that throughout this latest extremely lengthy and interesting PureTech presentation (I only skimmed through bits and pieces of it), one gets the feeling that hair loss is almost insignificant in terms of their overall focus. Medical issues take far greater precedence over cosmetic ones.

Follica Twitter Account Becomes Active Again

Recently the online hair loss world got very excited about Follica’s upgrade of its website with a goldmine of new information, including photos and product renditions. Follica also very recently restarted posting on its Twitter account after a lengthy break. They even followed this blog on Twitter after restarting the Twitter posts, so now I have to become much less skeptical about the company. How could anyone who follow’s this blog ever be fake?

Please read this post in its entirety. Also note that this blog has been having some issues lately with comment totals not updating until you refresh a few times or only if you use a totally different browser. I was trying to experiment with some caching plug-ins recently, and things did not work out as planned hence the current problems.

Dr. Jeffrey Rapaport Agrees to Offer Free PRP Treatments to one Blog Reader

I have discussed platelet-rich plasma (PRP) treatments on this blog many times in the past. There are now an increasing number of studies around the world that support PRP and its benefits towards scalp hair growth. At the recently ended 24th ISHRS Congress, there were around ten different presentations or training sessions related to PRP, including many from doctors outside the US.

I therefore decided to ask USA based Dr. Jeffrey Rapaport on whether he would be willing to grant a free PRP treatment session (will probably involve at least 2 sessions) to one of this blog’s readers. To my pleasant surprise, he has agreed!

The biggest complaint about PRP from numerous hair loss forum members and blog readers is that it is a ripoff considering that there are no guarantees that the treatment will work. So now we finally have a doctor who is confident in the treatment and willing to offer one person free session(s).

Will PRP regrow hair on totally bald regions of your scalp that have been barren for many years? No. Will it make existing hair stronger or even temporarily reverse miniaturization? I feel like there is now sufficient enough evidence that this is a good possibility, albeit never guaranteed.

PRP Prize Drawing Rules

This is the second ever prize drawing that I am posting on this blog. The first one for a laser helmet was a learning and very time consuming experience for me (make sure to read post 1 and post 2 regarding that first prize drawing). This one is even more difficult, but I hope to not spend as much time as before since most of you know the gist of the selection process.

1. As with the last prize drawing, please enter this contest by writing a comment to this blog post saying “I am in” or something related that is a few words long. You can add a reason for why you feel like you want the treatment, but it won’t sway me in my final decision as that is based on a random number generation. People posting double entries or irrelevant comments will be automatically disbarred from the final random prize drawing entry list. Relevant questions about this prize drawing or about the PRP procedure are encouraged. No insults whatsoever.
2. It is extremely important that if you enter, you are 100 percent certain that you can go to Dr. Rapaport’s clinic in New Jersey (US) for the treatment. You are responsible for all your non-treatment expenses including airfare, hotel, car rental and food. In all likelihood, you will have to go there for at least 2 treatments spread across a few months, so please refrain from participating if you can only go for one procedure. If possible, please add your US state or foreign country of origin in your comment. If you live outside the US or Canada, I might have to ask you some questions later since I find it hard to believe that someone would fly over to the US just for free PRP (in most countries where it is on offer, you can probably get a doctor to charge you $1,000 or so for each session).
3. If the last prize drawing was any indication to go by, there will be many people who comment for the first time just to enter the prize draw. Please try to use a legitimate e-mail address instead of a fake one (so that I can contact you), and do not use a common username such as “Mike”, “Matt”, “Jeff”, “John” etc…as those are often already used. At least add a number to such names if you use them (e..g., “Mike2016” is ok). Note that the e-mail address that you enter when commenting is only visible to me and to none of the other blog readers.
4. Dr. Rapaport will take before and after photos, and according to his assistant, they will have rights to the photos. The assistant told me that that if they post before and after photos online, they will remove the patient’s face from those photos. However, I am not responsible if this ever happens to you.
5. Dr. Rapaport can change anything at any point during the process if he feels the need to do so. e.g., he can postpone at the last minute if necessary even if you purchased an air ticket (you will not be refunded), he can choose to not have you come back for a second session because he has some issue with you, he can add other products such as ACell into the mix, he can use a different injection and centrifugation strategy to other doctors and so on. In the event that you have some kind of crazy reaction on your scalp, he will not be responsible. He is doing you a big favor by offering this treatment for free. You will not be allowed to insult him on this blog in the event that you have any kind of disagreement. If you win, please contact his office to make sure you know what you are getting into as far as the procedure goes.
6. While I have never heard of PRP treatments ever causing serious injuries to anyone, getting injections into your scalp and getting blood drawn out of you are both invasive procedures. I am not responsible for any side effects and injuries you get, and I am assuming that Dr. Rapaport’s office will make you sign waivers about such issues. You are taking the risk and should do all possible research about what is involved here before deciding to participate. If you have any hypochondriac tendencies, I would think twice before participating.
7. I will wait for anywhere from 5-10 days before closing entry. Then, like last time, most likely I will pick 5 or so names at random and then narrow down to the final 1 via another random pick (after weeding out any of the 5 potential winners that seem fake or suspicious or unresponsive to my e-mails).
8. Women are encouraged to participate since many doctors who offer PRP have in the past suggested that females respond better than males to the treatment.
9. Finally, if the winning candidate ends up seeing no results, he/she will be allowed to say so in a comment on this blog, although any insults will be removed immediately. Dr. Rapaport will be allowed to respond to any comments if he chooses to do so, including with the winner/patient’s before and after scalp photos.  Please remember that a large number of people who get PRP end up seeing no results whatsoever when it comes to their scalp hair, so you should go into this with appropriate expectations. In the past, a few people have even claimed that PRP made them lose some hair!

Hair loss news first:

— A very busy month for Aclaris Therapeutics. First the company updated its product pipeline page and added photos for each dermatological condition that the company’s various products are supposed to treat. Then they filed for Investigational New Drug Application (IND) for their oral alopecia areata product ATI-50001 with the US FDA. Then, on November 15th the company announced positive results for its topical seborrheic keratosis product (A-101) phase 3 clinical trials (webcast here); and finally, on November 16th the company announced a public offering of its common stock. If successful, the funds raised from this offering will partly be used towards research and trials for Aclaris’ JAK inhibitor products.

— In the past month, HairClone has added the well known Dr. Russell Knudsen, Dr. Robert Leonard and others to their clinic partner team.

— More good news for alopecia areata/totalis/universalis sufferers. This time its two patients from Brazil who were taking JAK inhibitor toafacitinib.

— Dr. Christophe Guillemat updated his blog a week ago. I am still skeptical about his work, but there is a huge amount of interest.  Someone commented in the past that he is not a doctor, but I am not sure. Also see my initial post on him.

— Sharp (Japan)’s plasmacluster ion technology promotes hair growth. Sounds hard to believe. The ending of the article about reduced dandruff and itching is more believable.

— Cellmid (Australia) raises sufficient funds to start selling its Evolis line of FGF-5 inhibiting hair loss products in the US.

— Hairdresser Chad Gunter is very pleased with his PRP results from Dr. Laura Bennack. According to Dr. Bennack, “the most dramatic results are on men and women who are at the early stages of hair loss”.

— Yet another growth factor (human hepatocyte growth factor) linked to promoting hair growth. Also see my recent post on the various growth factors that benefit hair growth.

— Kerastem has more US clinics participating in its clinical trials.

— Missed an important study’s findings last month: BPH drugs such as finasteride and dutasteride (both are also used to combat hair loss) do not raise the risk of erectile dysfunction.

— Wen hair care product lawsuit concludes in favor of customers.

And now on to medical items of interest:

— Gene therapy in a box courtesy of the Fred Hutchinson cancer research center.

— CRISPR gene editing tested in a person for the first time in China.

— “Any idiot” can now create mutant CRISPR engineered mice.

— Gene therapy to reverse certain types of genetically inherited blindness could be approved for use as soon as next year.

—  And thereafter, bionic superhuman eyes.

— Amazon’s Jeff Bezos partners with the Mayo Clinic and others to enter the anti-aging industry.

— Terminally ill 14 year old in the UK allowed to be cryogenically preserved. Also, a reality check.

— Samantha Payne’s Open Bionics allows anyone in the world to download and 3D print their own bionic limbs.

— Brain implants allow paralyzed monkeys to walk. The Swiss scientist goes to China to conduct this work due to friendlier regulations. More here.

— First at-home brain implant allows paralyzed woman to communicate.

— Genetically modified pig’s heart transplanted into a monkey in South Korea breaks prior world record. The monkey survives for 51 days. Pig’s hearts are thought to be a close match to the human heart. Very cruel animal experiments, but hopefully they help humans in future.

— Dr. Anthony Atala is still optimistic about printed organ replacements.

Please post thoughts unrelated to this subject matter in the comments section of the prior blog post.

I was surprised to get around 60 participants in the free PRP treatment prize drawing contest despite my discouraging people who reside far away from New Jersey from participating.

Instead of explaining the prize drawing winner selection procedure yet again, I prefer contest participants reading the winner selection post from the last time I ran such a contest. If you are lazy to do that or do not care about the details, I have pasted the main instructions paragraph from the above at the end of this post.

The 5 people that the random generation resulted in this time are as follows in alphabetical order (another random draw will be used to select the final winner from the below 5 once they respond):

— Emperor Alopecia (from NJ)

— Kana (from Canada — please confirm that you can make it for at least two sessions, months apart from each other)

— Michele99 (from NY)

— Robb (from the UK — please confirm that you can make it for at least two sessions, months apart from each other)

— Tom (from PA)

All 5 of you please post at least one comment in this thread using the same email you used last time and the same IP address/ computer/location that you used last time to post your comment. Also email me your full name and physical address from the same email address that you used for commenting. I will wait for two days for responses.

During the past year, I have received a few requests to write a detailed blog post on scalp micropigmentation (SMP), sometimes also termed as scalp hair tattooing. Earlier this year, I told several blog commentators who asked that I would try to do so by fall. However, I had to keep delaying this post due to other more pressing developments in the hair loss world as well as some laziness on my part in researching a topic in which I had very limited interest. In general, SMP is used to give a look of a shaven head that still has all its hair follicles (shadow) intact, although increasingly, people are also getting SMP to enhance the appearance of a hair transplant.

Because scalp micropigmentation procedures have become extremely popular during the past several years, I could not delay this post any longer. Moreover, one of the world’s most respected hair transplant surgeons e-mailed me several months ago and told me that I should write something about this subject matter as soon as possible because their was a lot of confusion in the field. He said that clinics were hiding their proprietary methods from competitors and their is no official regulatory governing body when it comes to the SMP world. i.e., the still nascent world of SMP is not at all transparent at present to the detriment of consumers. It should be noted that despite some bad work out there, numerous people have been very pleased with their SMP procedures and I have seen some superb before and after photos online. Just like with hair transplants and hairpieces, for some people, tattooed hair on their scalps is almost as good as a cure for hair loss. I think head shape and facial skin type/condition also impacts the final satisaction when it comes to SMP.

Tricopigmentation Versus Scalp Micropigmentation (SMP)

Immediately after I started researching this post, I realized that I might have to write at least two posts on scalp hair pigmentation/ tattooing procedures: one on tricopigmentation and one (or maybe even two) on scalp micropigmentation. This particular post will focus on tricopigmentation.

At a bare bones level of understanding, tricopigmentation is just a “temporary” form of “permanent” scalp micropigmentation. However, the definition of “temporary” and “permanent” varies depending on clinic and method being utilized. It seems like “temporary” tricopigmentation ink marks can last anywhere from 6 months to 2-3 years. At the same time, some (but not all) of the so-called “permanent” ink marks in SMP can fade or even disappear within 5 years and often require further touch-up procedures. However, I will save the details of the SMP discussion for another post.

Milena Lardi, Beauty Medical and Tricopigmentation

The person that is most widely associated with tricopigmentation is Italian Milena Lardi, the founder, teacher and technical director at Beauty Medical (Italy). While I am not sure if Ms. Lardi is the inventor of temporary forms of scalp hair tattooing (surely many people must have tried in the past?), she has nowadays become synonymous with the term “tricopigmentation”. Her reputation in the industry seems to be unmatched and stellar. However, it does not seem like she has any kind of registered trademark or copyright to the name “tricopigmentation”. As a side note, HIS Hair Clinic claims to be the world’s first company that offered SMP, 14 years ago. However, even they do not seem to have the rights to the term “scalp micropigmentation”.

According to Ms. Lardi’s Beauty Medical website, tricopigmentation is performed in the upper layer of the dermis. Note that the dermis is the second layer of human skin beneath the epidermis first layer. Skin damage to the epidermis can often be reversed, but skin damage to the dermis is much harder to reverse. It is therefore crucial to do thorough research before embarking on a scalp tricopigmentation procedure. According to Beauty Medical, “tricopigmentation is reversible, non-allergenic and bio-compatible thanks to the use of specific pigments which can be absorbed by the body”. The pigments are microscopic and in the shape of dots. Most patients will require at least one touch-up procedure within the first year after the initial tricopigmentation procedure.

Is Temporary the Superior Choice?

According to numerous online opinions, temporary hair tattooing (aka tricopigmentation) is the way to go while permanent hair tattooing (aka SMP) is too dangerous. At first glance this seems obvious, just like with any form of body tattooing. However, permanent SMP does offer its own advantages that I will discuss in an upcoming post, and there are numerous clinics around the world that offer SMP. If there were hundreds of customers having major regrets several years after getting SMP procedures, we would be seeing far more online negativity as well as lawsuits against clinics by now. At the same time, SMP is far too recent a procedure to know for sure what people will feel like 10-20 years down the road (when the complaints might really proliferate), and for now I would definitely go for temporary over permanent if I had to choose. But I am always very conservative in such matters. In 2014, Dr. Arvind Poswal (India) who got training from Milena Lardi started an excellent thread on Hairsite about this subject and Ms. Lardi also posted a detailed response in there towards the bottom. Both of these two professionals seem to prefer temporary tricopigmentation to permanent SMP.

Having said all that, please stay tuned for my future post on SMP since it is probably a bit biased on my part to favor temporary over permanent without as yet having even completed my research on SMP.

Tricopigmentation in Combination with a Hair Transplant

Numerous hair transplant surgeons have now started to offer tricopigmentation in tandem with a hair transplant in order to make the final results even better, especially in those with extensive areas of baldness that can not entirely be covered with a hair transplant. It seems like most hair transplant surgeons prefer tricopigmentation over SMP. One surgeon e-mailed me that his clinic offers procedures that can last 1-2 years, or 3-4 years, but anything permanent is not good. I will add more here if I get feedback on details regarding when ink lasts 1-2 years versus 3-4 years. Of course some of that will depend on the biology of individual patients and their scalps as well as their lifestyle. Rain will not remove the ink, but too much direct sunlight can potentially impact the duration of results it seems.

One blog reader e-mailed me in the past that he was curious if a scalp micropigmentation procedure could cover his bad linear scar at the back of his scalp from a strip (FUT) hair transplant procedure. That is an interesting idea and Dr. Poswal has a good video on the viability of such a procedure.

Tricopigmentation Technique Variations

Tricopigmentation techniques vary depending on clinic and practitioner. The two main differences are probably in the type of ink/pigment used and in the type of tools used. I doubt that the depth of treatment varies too much between experienced practitioners when it comes to temporary scalp hair tattooing, but I will refrain from making any conclusions here. It is imperative that one goes to a highly reputable and experienced person or clinic for this treatment in order to get a quality hairline design and ensure a natural looking appearance. Some clinics claim to use software and computers (which reminds me of the ARTAS hair transplant robot, although that is much more sophisticated and expensive). Beauty Medical has proprietary “Trico Skin Care” machines and 0.2 milimeter diameter “Tricoinjector” needles which it sells to practitioners that it has trained and licensed. It seems like the machines are set to inject at precisely 0.5 millimeter depth each time with no room for variation (as would be the case with purely human hands and no machine assistance).

Here is a a good overview of what is involved in the tricopigmentation procedure.

I will add more details to this section and the one(s) below as I get more responses from clinics.

Type of Ink used in Tricopigmentation

According to Milena Lardi from the earlier link that I posted in red:

The pigment is composed of a powder part and a liquid part:

Powder part = iron oxide and titanium bioxide.
Liquid part = water, alcohol, isopropyl and glycerine (coming from soya).

Cost of Tricopigmentation

The cost of tricopigmentation varies depending on area that needs to be covered. Online estimates seem to generally range from $1,000 to $4,000 per session.

During the past several years, the single biggest breakthrough in hair loss treatments has been in the form of Janus Kinase (JAK) inhibitors curing alopecia areata (AA), alopecia totalis and alopecia universalis in most test patients. You can find numerous posts on that subject on this blog if you browse through the categories menu.

While JAK inhibitors seem to be close to a cure for a majority of patients suffering from alopecia areate (as well as from many other autoimmune related disorders such as vitiligo,  psoriasis and rheumatoid arthritis), their effect on patients with androgenetic alopecia (aka male pattern hair loss, which is by far and away the dominant variety of hair loss in humans) is unproven and controversial to put it mildly. A US based company named Aclaris Therapeutics (based on the work of Dr. Angela Christiano) has claimed that there is a good chance that specialized covalently bound topical JAK inhibitors will cure androgenetic alopecia (AGA) in many patients (oral JAK inhibitors do not work for AGA but do work for AA). The implication is that male pattern hair loss might have a significant autoimmune component to it, a conclusion that it seems is not supported by many hair loss researchers. It is also possible that topical JAK inhibitors could be helping hair growth via a totally different mechanism unrelated to the immune system.

Cyclosporine A and Hair Growth

Some time ago, I mentioned a study that showed oral cyclosporine A (also referred to as ciclosporin A or as CyA) to benefit scalp hair growth in some men with androgenetic alopecia. I thought it significant that well before JAK inhibitors came on to the scene, there was already a drug int the form of cyclosporine that targeted the immune system and that seemed to benefit scalp hair growth in some patients. However, several bloggers mentioned that topical cyclosporine experiments by some hair loss sufferers did not seem to lead to any decent results insofar as scalp hair regrowth goes. Moreover, the effect of JAK inhibitors versus that of cyclosporine is very different (more on that further below), and the past studies linking cyclosporine and hair growth are somewhat ambiguous (more on that further below). I therefore decided to relegate cyclosporine to the backburner for a future post and forgot about it until….

RiverTown Therapeutics’ new Website

The biggest news in the hair loss world this month has been RiverTown Therapeutics’ new website. I have generally not been too keen about this company even though I have mentioned them several times in my blog posts this year.

My two biggest reasons for being pessimistic about RiverTown are the facts that:

1. Minoxidil by itself can give great results in terms of hair growth in some people (so their Minoxidil containing RT1640 product could just be glorified Minoxidil). And a company named Follica (US) has already tried a wounding plus Minoxidil approach that is likely superior to just Minoxidil.
2. RiverTown has not even conducted phase 1 clinical trials for RT1640 at present per their product pipeline page, and by the time all 3 clinical trials are concluded, we could very well have a few more superior treatments on the market (Follica, Histogen, Tsuji, Shiseido and more).

Adding to my skepticism about RiverTown are small details such as its actual home page still saying “under construction” as of today, and the CEO’s Linkedin profile not even having RiverTown listed in there (I thought it was there in the past?).

Having said that, I was pleased to learn that the respected hair loss researchers Dr. Elaine Fuchs and Dr. Maria Hordinsky (the former has been mentioned on this blog many times before) are both on RiverTown’s scientific advisory board. Moreover, HLT forum member “Xaser94” made an excellent discovery that should have attracted far more attention: RiverTown’s CEO David Weinstein was previously associated with a company named GliaMed, and they had a product called GM1485 that never came to market, but that supposedly (in animals) promoted “the regeneration of all components of the skin after injury, including nerves, hair follicles, blood vessels, dermis and epidermis with minimal scarring”. Encouraging.

Hopefully the fact that last week the US House of Representative overwhelmingly supported the passage of the 21st Century Cures Act will help RiverTown and other companies in the hair loss world bring forth their products to market significantly faster, without having to move to Japan.

In any event, getting back to the subject matter of this post, the reason I mention RiverTown is because the new website clarifies that the company’s RT1640 hair loss product contains three ingredients, one of which is cyclosporine A:

• Minoxidil (already FDA approved).
• Cyclosporine A (already FDA approved).
• RT175 (a proprietary chemical entity developed by one of Rivertown’s co-founders that has been tested in 600 humans).

Cyclosporine A and Hair Loss Studies from the Past

So now I had to look up all the past studies that mention Cyclosporine and hair in the same page. Below is a chronological list of the most important such studies, with my notes in blue.

• Cyclosporine and Male-Pattern Alopecia, 1987 (US). Just 1 patient, but a very positive result with new hair growth in the temporal region of the scalp when on cyclosporine, which then went away when off the drug. An interesting quote: “Hypertrichosis has been reported to occur in 60% of kidney transplant recipients treated with cyclosporine”. Hypertrichosis means excessive body hair. If something can grow new body hair (or convert vellus body hair to terminal body hair), it is surely not out of the realm that it can also grow new scalp hair? It should be noted, however, that cyclosporin might be increasing DHT levels and that could be increasing body hair.

• Topical Cyclosporine in Male Pattern Alopecia, 1990 (Israel — from the prestigious Technion University). The now deceased forum member Bryan pasted the whole study for is on HLH. 2 out of 8 human subjects who suffered from AGA saw significant growth when on topical cyclosporine for 4 months. One 1 of those 2 saw cosmetically evident growth. Same authors have another study from 1988 based on transplanted human hair onto mice, and they concluded that cyclosporine A may be effective in the treatment of alopecia.

• Effects of Cyclosporin A on Hair, 1994 (Germany). A very interesting statement in “One of the most common dermatological side effects of oral CyA is dose-dependent hypertrichosis”. It seems like CyA causes new body hair to develop from vellus hair. Also, the conclusion is that oral application of CyA proved successful in treating AA as well as AGA (!). However, the topical application failed to treat either condition.

• Hair Growth-Stimulating Effects of Cyclosporin A and FK506, Potent Immunosuppressants,  1994 (Japan). A bit confusing in that they seem to discuss body hair and scalp hair alternately. In any case, they state that “the hair growth stimulating effect of CsA is observed not only in normal but also in pathological conditions of hair growth, i.e. in patients with alopecia areata and also in some patients with male-pattern alopecia“.

• Oral Cyclosporin Does not Arrest Progression of
  Androgenetic Alopecia, 2001 (Australia). Unfortunately, the news is not always positive:-( Abstract not available for me to see how many patients were involved.

• Cyclosporine A Increases Hair Follicle Growth by Suppressing Apoptosis-Inducing Factor Nuclear Translocation: a New Mechanism, 2015 (China).

Cyclosporine A Versus JAK inhibitors

While cyclosporine A and JAK inhibitors both have immunosupressive properties, their mechanism of action is different.

According to the earlier mentioned Japanese study, cyclosporine A inhibits T-cell activation by “interfering with the production of interleukin-2 (IL-2) by inhibiting IL-2 gene expression, probably through the inhibition of calcineurin, a Ca2+/calmodulin-dependent phosphatase”. A bit difficult but not impossible to understand. Cyclosporine is used for a number of inflammatory skin conditions, especially psoriasis.

JAK inhibitors are a type of medication that inhibit the activity of one or more of the Janus kinase family of enzymes (JAK1, JAK2, JAK3, TYK2). In the process, they interfere with the critical JAK-STAT signaling pathway. Aclaris is working on a  topical covalently binding, highly selective JAK3 inhibitor to cure AGA.

I hope the five or so scientifically highly astute commentators that we have had on this blog to date can further compare and discuss JAK inhibitors versus CsA, since my knowledge in this area is very limited.

My Hypothesis

Over the years, I have read numerous online forum posts from people stating that when they started losing their hair, they also started getting a lot of scalp itching (largely in the same areas where they were also experiencing hair loss). I have witnessed the exact same phenomenon on my own scalp and use Nizoral to tackle the problem whenever it arises.

This has led me to wonder whether people who have male pattern hair loss combined with a lot of associated itching, inflammation and dandruff also have an autoimmune component to their hair loss? Perhaps men with male pattern hair loss can be divided into two broad categories: those with an autoimmune component to their hair loss (and itchy scalps), and those without any autoimmune component (and normal scalps with no itching) ? The fact that both the immunosuppressant drugs CsA and JAK inhibitors can help some men with male pattern hair loss makes this hypothesis less far fetched than it might have originally seemed in my opinion.

2% and 5% Strength Minoxidil

When Minoxidil was first approved by the US FDA to treat hair loss in 1988, it came in a 2% topical solution format under the brand name Rogaine. The product had been used for many years prior to approval as an off-label hair loss treatment. In 1997, the FDA approved a higher strength version of Minoxidil in the form of a 5% topical solution that could only be obtained via a prescription, although that requirement was soon thereafter waived in 1998. After Rogaine’s patent ran out, newer generic versions of Minoxidil have come onto the market. More importantly, the topical version (thought still available) has been superseded by a drastically superior foam version that does not run down onto one’s face (sometimes leading to tiny hair growth on the forehead!) or cause major itching.

I hated using topical Minoxidil, but love using the foam version as it acts like a mild gel and is not messy like the topical version. Minoxidil 5% foam has helped my hair for sure, and usually within an hour of application, I find my that my hair feels thicker and fuller. I am certain that this is not a placebo effect. While you are supposed to use Minoxidil twice a day, many people just use it once a day. Note that Minoxidil is also used by females and women’s 5% Rogaine foam was launched in 2014. Also of significance, Minoxidil still remains one of only two ingredients (the other being Finasteride) that have ever been FDA approved to treat hair loss.

15% Extra Strength Minoxidil

While 5% Minoxidil was initially considered to be a high strength version of the product, this is no longer true. A number of companies sell 15% (and in some cases, 10%) versions of the product, but I have never tried those. I assume most of these companies will require a prescription before they can sell it to you (and maybe it might even be illegal for them to sell in some countries such as the US). Minoxidil was originally used as a blood pressure medication, so if you ever use such a high strength product, buyer beware and make sure you measure your blood pressure regularly since the topical product does get absorbed systemically. When on Minoxidil 5% to treat hair loss, some people have complained about various side effects such as skin problems, an increase in body hair, water retention and more. Such side effects will probably be exacerbated when on 15% Minoxidil.

Two of the better known companies that currently sell Minoxidil 15% are Xandrox (based in Canada) and MinoxidilMax. While the latter has some bad pages on its site with missing information, their 10 most popular questions section at the bottom of the home page is worth a read.

Dr. Richard Lee — Minoxidil 15% plus Azelaic Acid

The original high strength Minoxidil guru was a US-based doctor by the name of Richard Lee. I heard about his name on a regular basis on hair loss forums throughout the 2000-2010 period. He compounded an extremely popular high-strength 15% version of Minoxidil in the 1990s and added azelaic acid to it due to the latter’s anti-DHT (dihydrotestosterone) properties. Since he got an online presence very early on in the internet’s infancy, Dr. Lee’s business took off with a flourish and he had zero competition. However, in 2011, the at-the-time 72-year-old Dr. Lee started having problems with the US FDA and had to close his Regrowth LLC company. Case details here.

An interesting old Discovery Channel video with Dr. Richard Lee in there:

Dr. Oscar Klein — Minoxidil 15% plus Tretinoin (Retin-A)

Another US-based doctor by the name of Dr. Oscar Klein also became extremely popular for selling a reputable 15% Minoxidil based product that also contained Tretinoin (more widely known in the hair loss world by its trade name Retin-A). While Dr. Klein unfortunately passed away in 2014, his Hair Growth MD company still sells his Remox brand products.

A video of Oscar Klein from a 2003 NBC interview:

Even Higher Strength Minoxidil

Polaris Research Labs’ NR-10 product contains 16% Minoxidil. However, the company’s website does not mention where it is headquartered, but does say that the product is not available for sale in the US. I would try to learn more about this company before considering them.

The Medical Wellness Center online pharmacy supposedly offers up to 30% Minoxidil content lotions and creams. Belgravia Centre in the UK offers “high strength” Minoxidil. Please check with a physician before ordering such products to ensure legality and safety.

You can also go to local compounding pharmacies and they might be able to compound 20% or higher Minoxidil for you. However, this may not be particularly safe for long-term use, and there is a good chance that 20% will not be any more effective than 15%.

Minoxidil in the News Recently

One of the reasons I chose to write this post is because Minoxidil has been in the news recently, with two companies either experimenting using it (Follica — although I highly doubt that it will be the main product in their final yet to be released product) or actually using it (RiverTown Therapeutics). Sometimes it is easy to forget that the synergistic effects of Finasteride and Minoxidil have essentially been a cure for hair loss for numerous people, especially when used in the earlier stages of hair loss.

Hair loss news first:

— As expected, on November 30th the US House of Representatives passed the groundbreaking 21st Century Cures Act with a high level of bipartisan support. This Act has been discussed on hair loss forums fairly regularly over the past year since it would allow for faster times for hair loss drugs and stem cell therapies to come to market without the need for completion of extensive phase 3 clinical trials. I think this development will also prevent more western pharmaceutical, medical device and stem cell therapy related companies from moving research and development activities to Japan, where a somewhat similar Act has already been passed. There are still a lot of uncertainties on the final regulations, and the rules could always end up being stricter for products related to cosmetic conditions such as hair loss. Wired magazine calls this development “inject and see” and warns of the obvious dangers of such an approach for patients.

— I covered firefighter Pat Hardison and his full face transplant before. I did not realize that he also got a full new head of hair and not just a new face. Seems like the audience cheers him for his new hair even more so than for his new face a few minutes into the below video:

— On Twitter, Dr. Alan Bauman recently posted an unbelievable before and after photo of a hair loss patient who was treated with adipose-derived stem cells (ADSC). The photo was from a Boston Biolife led presentation at the recent World Stem Cell summit held in Florida in early December. I contacted Boston Biolife and they said the doctor who made this presentation might send me the actual full presentation if I e-mailed him, but so far no response. I would normally consider such a great result from ADSC to be a scam or a one-time exceptional case that does not warrant too much discussion, but I ended up including it here because the presentation was made at reputable stem cell summit by what seems to be a reputable organization:

Can adipose derived #stemcells help regrow hair? @bostonbiolife lecture seems to suggest this! @WSCSummit #WorldStemCellSummit pic.twitter.com/wQnR8cMPdj

— Alan J. Bauman, M.D. (@DrAlanBauman) December 6, 2016

— On December 7th Aclaris Therapeutics announced that it had initiated phase 1 clinical trials for its ATI-50001 JAK inhibitor product to treat alopecia totalis and alopecia universalis.  Also, in late November they had an earnings call, with the most relvant part for us pasted below:

“In addition to progressing our JAK treatment program for the treatment of alopecia areata and as we reported on our last call, we have initiated preclinical development of additional JAK inhibitors which we are developing for topical use both in vitiligo and androgenetic alopecia, which is also known as male or female pattern baldness. The program includes the development of ATI-5003, which is a covalently binding JAK3-specific inhibitor, and the preclinical and formulation work continue to progress as expected.”

— New study from Germany: “Hair follicle stem cell cultures reveal self‐organizing plasticity of stem cells and their progeny“.

— Rafael Nadal gets a hair transplant.

And now on to medical items of interest:

— World’s oldest woman turns 117 and credits an eggs and cookies diet combined with no husband.

— I covered the crazy skin gun video from 2011 on this blog before. After five years of waiting, it seemed like the concept was a fantasy and would never take off. Now the US based company that is behind this product, RenovaCare, has been awarded a patent for its skin gun technology. And they also got covered by CNN this month.

— 3D printed organs look, feel and bleed like the real thing.

— Dementia (including Alzheimer’s) could soon be treatable. Or at least stabilized and manageable.

— Mice lifespans extended by 30 percent and organs rejuvenated via reprogramming the genome of mice. Actual study.

— Some new information on Google’s Calico.

— More good news on diabetes drug Metformin, which also helps with cancer treatment. This drug has been in use for over 60 years.

— New “liquid biopsy” chip to detect cancer from a drop of blood.

Note: Voting buttons are below each of the two photos for the two polls and you can only vote once via hovering over and then clicking on the appropriate row (you can only see vote totals in each row after you vote). Be careful about touching or clicking an answer by mistake as you scroll down since you cannot change your initial vote like I allowed in the past.

Been a while since the last poll. Two polls below related to the price that you would be willing to pay for a hair loss cure. A “cure” means maintaining your existing hair as well as getting back the vast majority of your lost hair. In the first poll, you can assume a “session” of treatments to mean a few treatments (most likely to be scalp injections, but perhaps even genetic therapies) that are spread out across up to a year; and “permanent” to mean robust quality hair that lasts for at least a few decades. Note that the first poll question is about a one-time payment. In the second poll, however, the question is in relation to monthly payments for the rest of your life.

Poll 1

Poll 2

I was considering writing my final post of 2016 on things to look forward to in 2017. However, I felt it would be somewhat repetitive in nature. New announcements from any of the companies mentioned in the 5 bullet points in this post are the most important things to look out for in 2017 and I did not want to repeat that information here. Allergan and Samumed are also of significant interest to the hair loss world. Various other lesser known usually newer companies involved in clinical trials and/or new hair loss related drug development are also worth keeping an eye out for, although some are receiving a level of publicity way beyond what they currently warrant. e.g., this record 314 (and counting) page thread about a somewhat unproven product is insane. And finally, the 5-10 major regional and global hair and/or stem cell related conferences are always of interest every year including in 2017. We should all also be watching out for CRISPR and gene modification related conferences hereon.

But to end this year, I wanted to find something else to write about that was unique, not repetitive, and not too technical/scientific in nature. Something you can read on your phone screen on New Year’s Eve while drunk and out in the cold waiting for things to happen. After some consternation and difficulties in deciding on what to write about, lo and behold, Joe Tillman (formerly known as Jotronic) and Spencer Stevenson (more widely known as Spex) unknowingly came to the rescue. To learn more about both these hair legends, please read my original post on them.

Joe and his 25,000 Transplanted Hair Follicles

First, earlier today Joe Tillman released an excellent and very instructive video for those who are thinking of getting a hair transplant. I did not realize that he has had 25,000 (!) hair follicles moved from the back of his scalp to the front and crown of his scalp over the years (in 6 separate surgeries). Note that “follicles” is different from “follicular units” or “grafts”. Joe’s transformation has been very impressive and he is very honest about all the pros and cons of his “new” transplanted hair. I still cannot believe his before and after hair transplant transformation considering that his first two bad hair transplants occurred over 20 years ago. FYI — click on the title of the below video to open in a separate page.

Spex Joins the Dutasteride Bandwagon

I have mentioned Spencer (Spex) a few times on this blog before. He has had around 10 (!) large and small hair transplants over the years and is featured in numerous newspaper stories about hair loss. I was very pleased to learn that he very recently started using Dutasteride to treat his hair loss. He is documenting his results with photos here.

I have discussed Dutasteride (original brand name = Avodart) numerous times on this blog. It is basically Finasteride (original brand name = Propecia) on steroids. More benefits as well as more side effects than Finasteride. There are quite a few internet testimonials that you can find of old men who got on Dutasteride (to treat enlarged prostates) and saw hair growing on parts of their scalp that were bald for decades (something that is extremely hard to do). You can also read about some great positive results (as well as failures) of using Dutasteride to treat hair loss in the comments to this post.

When Dutasteride (Avodart) first came out onto the market in 2002 (after FDA approval at the end of 2001), hair loss forum members all over the world were going berserk with excitement. I miss those days when it seem liked Dutasteride was the ultimate cure for hair loss and everyone was counting the days till the pending product release with extreme levels of hope and hysteria. Unfortunately, the drug was not a miracle for most people who already had significant hair loss.

So instead of hairlosscure2002.com, here I am talking about hairlosscure2020.com

Happy Holidays Everyone!

Addendum: This week, 47-year-old eccentric Vassily Ivanchuk won the world rapid chess championships, the domain of much younger men. Of late, he has mostly been focusing on becoming a great checkers/draughts player. The greatest year ever in the search for a hair loss cure and now this icing on the cake. It will be hard to beat 2016.

Dutasteride 0.5 mg per day Significantly Superior to Finasteride 1 mg per day at Regrowing Hair

Dutasteride 0.5 mg per day Significantly Superior to Finasteride 1 mg per day at Regrowing HairA new study from India shows that Dutasteride 0.5 mg once a day increased hair count in 45 men from 223 at baseline to 246 at 24 weeks (i.e. in 5.5 months of treatment). Full highly detailed study here. This represents just over a 10 percent increase. It should be noted that without any treatment, most people would continue to lose hair, so the real benefit is greater than 10 percent.

In the same study, 45 men were also treated with Finasteride 1 mg once a day and saw about a 2 percent increase in hair count at 24 weeks. Still a good results when considering that virtually all of these balding men would have seen a decline in hair count at 24 weeks without treatment.

Before and after photo of best case result of Indian patient taking Dutasteride 0.5mg daily for 24 weeks (Source):

This is yet one more study among numerous others over the past decade that has concluded Dutasteride to be significantly superior to Finasteride in regrowing hair. The majority of such studies seem to come from the western world (with Japan and South Korea also disproportionately represented) so I am glad that this one comes from India. It seems like Dutasteride is effective at growing hair irrespective of one’s ethnicity and genetics.

I liked the below finding (although it should be noted that Dutasteride is still too recent a drug to make any conclusions about long-term side effects; and most other studies show at least slightly higher side effects from Dutasteride compared to Finasteride):

Both the groups showed a similar side effect profile with sexual dysfunction being the most common and reversible side effect.

Dutasteride Regrows Some Miniaturized Hair

One of the more interesting aspects of this particular study is that the authors also measured how many miniaturized/miniaturizing hairs (i.e., “thin hair count”) became thick once again. This is important because it shows that 5-alpha-reductase inhibitors such as Finasteride and Dutasteride can bring back hair from the dead/almost dead/slowly dying. It is unclear how many if any of the thin hair that became thicker were vellus hair (i.e., barely noticeable and almost transparent) that had shrunk many years or even decades earlier. In this particular study, Dutasteride 0.5 mg led to a reduction in the “thin hair count” by 12 percent at 24 weeks, while Finasteride 1 mg led to a reduction in the thin hair count by 1.5 percent at 24 weeks (just a 1 unit reduction in actual thin hair count so not too meaningful a percentage figure interpretation here).

Over the years, I have read many online anecdotal reports (see links at end of this post) of older men who were taking Dutasteride to treat enlarged prostates and saw hair growth in areas of the scalp that were totally bald (i.e., covered in vellus hair) for decades. Dutasteride likely helps bring back long-lost hair in many patients, although usually just some of it.

***If you ever do decide to take Dutasteride, I would highly recommend consulting an experienced dermatologist first and being aware of the worst case potential side effects.

Several weeks ago, the arrector pili muscle got significant coverage in a few newspapers around the world. Famed Australian dermatologist Dr. Rodney Sinclair co-authored an important paper titled “The arrector pili muscle, the bridge between the follicular stem cell niche and the interfollicular epidermis” that was just published this month. Dr. Sinclair has been involved in this area of hair loss research for a few years and already published similar findings several times in the past decade. Nevertheless, Australian newspapers were especially interested in this latest study and its findings as evidenced by articles such as this one and this one.

The Arrector Pili Muscle

Arrector pili muscles are small muscles attached to individual human hair follicles on both the scalp as well as body (so we have millions of these muscles throughout our bodies). Contraction of these muscles causes hairs to stand up, a phenomenon that is known as goosebumps. Therefore, the arrector pili muscle is often referred to as the goosebump muscle.

The Arrector Pili Muscle Degeneration and Hair Loss

In recent years, a few studies have come out that suggest a possible connection between the arrector pili muscle degenerating (where it gets replaced by fat) and hair loss due to the subsequent disconnection between various hair follicle stem cell populations. It is possible that an intact arrector pili muscle plays a crucial role in the maintenance of follicular integrity and stability.

However, there are many uncertainties about this theory that I discuss in the next section. It seems that while in alopecia areata (AA) patients the arrector pili muscle remains intact, this is not true in androgenetic alopecia (AGA) patients (and unfortunately over 95 percent of balding men suffer from AGA). So this could be why it is much easier to grow back hair for people with AA compared to people with AGA. However, the rate at which the arrector pili muscle degenerates and gets replaced by fat varies substantially between patients and between individual hairs on the same scalp. Some miniaturized vellus hairs in balding regions might even never lose most of their arrector pili muscle connection.

Points of Contention

• According to Dr. Sinclair’s own quote from a past paper, “It remains unclear whether arrector pili muscle regression is a cause or effect of permanent follicle miniaturization“. I think this is the crux of the issue surrounding this theory/hypothesis.
• It seems like hair that is transplanted from the back of a person’s scalp to the front of that same person’s scalp regenerates the arrector pili muscle. A very important related study from 2012  comes to us from Japan. So it might be very possible to regenerate this muscle.
• There are 100s of anecdotal reports on the internet of people regrowing long-lost hair. On the internet, you can find many reports of old men who recently started taking Dutasteride for enlarged prostate issues and have subsequently noticed hair regrowth on areas of their scalps that have been totally devoid of any visible hair for decades. Maybe they regenerated their arrector pili muscles; or maybe their arrector pili muscles always remained intact in spite of severe AGA; or maybe one can regenerate hair without the need for having any intact arrector pili muscles?
• It is unclear when exactly we have a point of no return where the arrector pili muscle is largely or entirely replaced by fat and hair stops growing (either as a cause or effect — see first bullet point above). It seems like there is significant variation depending on person and hair follicle. In many cases, the arrector pili might not be entirely degenerated and replaced by adipose tissue even in areas of the scalp where one has been bald for several decades. In such cases, subsequent hair and muscle regeneration could perhaps even be possible via something like Dutasteride or Finasteride?

It would seems that just as with out bodies, muscle beats fat yet again. However, as is always the case in the world of hair, nothing is ever straightforward! Even fat has significant hair growth benefits in the correct circumstances.

Hair loss news first:

— Replicel’s CEO provided a detailed 2017 forecast, and this was followed up by the release of an important PowerPoint presentation in which the company summarized final 5-year safety and efficacy data for their RCH-01 product. Key finding: “mean change in total hair density at 6-months = 6.1% vs 5.0% target“. 70 percent of responders saw a 14.3% average increase in density at 6-months. While they did not mention 12-month RCH-01 results, they do point out 12-month results from Finasteride (7-14% increase in hair density) and Minoxidil (8-16% increase in hair density) for comparison. Also, Replicel partner Shiseido’s Japanese clinical research findings are expected in 2018 along with a potential product launch in the same year.

— Aclaris Therapeutics made yet another presentation (pdf downloadable from their press releases page — I did not listen to the webcast), this time at the 35th Annual JP Morgan Healthcare Conference. At the end of the report they mention that pre-clincial development is now underway for their topical ATI-50003 selective covalently binding JAK 3 inhibitor to treat androgenetic alopecia. However, nothing in the report mentions when they aim to start phase 1 clinical trials. I hope it will be before the end of 2017.

— Follicum announced patent approvals in Russia and in Japan. The company had earlier also announced that they were scheduled to complete the multiple dose part of their clinical phase I/IIa study in January 2017 at the prestigious Charité University Hospital in Berlin.

— Judging from the latest update from Fidia Farmaceutici (Italy), The Dr. Brotzu lotion will not come out as early as some people expected, and a lot of people on the forums got mad (but a few took it as a positive sign that Fidia is finally releasing dates even if ambiguous — “development of the potential product candidate being completed by 2018“). Ever since I first wrote about Dr. Brotzu, I have not paid much attention to this product, but if you are inclined, go through the last 50 or so pages of this record breaking HLT thread and check out the various Italian hair loss forums out there.

— Also from Italy, some kind of PRP plus insulin type of treatment (hard to tell for sure after translation).

— Researchers identify how skin cells become hairy or sweaty during the embryonic stage of development. Actual study.

— This guy got a hairpiece and over 2 million youtube views in the process. He is probably someone famous, but I did not feel like doing any background research or even watching most of the video.

And now on to medical items of interest:

— From a team led by the most famous hair loss researcher in the world Dr. George Cotsarelis (who has been at it for at least 20 years), comes a new study on how to heal wounds without leaving any residual scars. Key quote from Dr. Cotsarelis: “Essentially, we can manipulate wound healing so that it leads to skin regeneration rather than scarring. The secret is to regenerate hair follicles first. After that, the fat will regenerate in response to the signals from those follicles”. I have discussed the link between fat cells and hair cells many times on this blog, including in the last post on the arrector pili muscle. These latest findings were widely covered by the global media, with headlines such as “The End of Scars“. The Reddit thread on this blew up. However, as with all things Cotsarelis, headline grabbing findings, but one always gets the feeling that practical use will be at least a decade away unless other labs get in on the action.

— Babies born without mothers (via embryos made from male skin cells) will come sooner than expected warn scientists. Surreal.

— Designer babies: an ethical horror waiting to happen? I am all for it even if it turns out horrific.

— Alzheimer’s drug “tideglusib” helps rotten teeth regenerate, reducing the need for fillings.

— Chinese company implants 3D prints blood vessels into monkeys.

Earlier this month, an interesting new study was published in the Experimental Dermatology journal by UK based scientists. The title of this study was “Hair regrowth in male and female pattern hair loss does not involve the conversion of vellus hair to terminal hair“.

Basically, the scientists found that when medications such as minoxidil, finasteride and anti-androgens were used to treat hair loss patients (both men and women), the resulting hair regrowth was almost entirely attributable to the reactivation of dormant non-vellus hair follicles (termed as “kenogen” hair follicles) rather than the conversion of fine miniaturized vellus hair into thick terminal hair.

This is a very surprising finding since in both male pattern hair loss (MPHL) and female pattern hair loss (FPHL), terminal hair miniaturizes via shorter and shorter growth cycles and finally becomes vellus almost invisible fine hair. I am pretty certain that it has long been assumed that hair loss medications cause some of these vellus hair to become terminal hair once again (if I have time later this week, I will try to find studies in support of such a theory). However, this latest study suggests something entirely different by concluding that:

We would propose there is a population of growth restricted (dormant/kenogen) non-vellus hair follicles, which are re-activated by effective medical treatments as an explanation for the increased hair growth observed in FPHL and MPHL. Our findings have a fundamental impact on the pathophysiology of hair changes occurring in patterned hair loss.

Hair Follicle Growth Cycle and Phases

We have all heard of the three main phases of the hair follicle growth cycle in anagen (growth), catagen (transition/regression) and telogen (resting). There is also a lesser known phase called exogen, which is when hair follicles undergo shedding

However, I had never heard of this new kenogen phase before. A basic google search showed that while this phase is almost never mentioned in literature, it was discovered as early as in 2002 when a study titled “Kenogen. A new phase of the hair cycle?” was published in Italy.

I am not sure if just several studies on this are sufficient to make any conclusions, but it is hard to believe that there could be some follicles in a dormant state that were previously unaccounted for and that are being reactivated by hair loss medications.

I have covered Dr. Alexey Terskikh (who works at the Sanford-Burnham Medical Research Institute in California) a few times in the past on this blog before. My main post on him and his pluripotent stem cell related work from almost exactly two years ago can be read here.

Recently, commentator “Sets” has contacted me a few times in order to see if I, with his help, can set up an interview with Dr. Terskikh. “Sets” is in regular touch with Dr. Terskikh on Facebook and has been acting as the in-between contact person between myself and the doctor/researcher.

I tried to contact Dr. Terskikh several times in the past, but he never responded until recently (and that to an e-mail I sent him 7 months ago after “Sets” asked him to look for it!). It seems like the doctor is easier to contact via Facebook, which I have not used in 1.5 years, so “Sets” is doing the grunt work for us. Please do not e-mail Dr. Terskikh as I am sure he gets 100s of them every day and is highly unlikely to respond in any great detail if at all.

In any event, if you have any questions that you want to ask Dr. Terskikh, please post them in the comments to this post and I will pick the most scientific/technical ones as well as the most interesting non-technical ones to ask him. Of course his willingness to respond will be dependent upon “Sets” much more so than upon myself:-(

On Twitter Dr. Terskikh has mentioned the need to raise $3 million to $5 million in funding in order to proceed with his team’s groundbreaking stem cell based hair growth related research. In his recent e-mail to me, he said they need $1 million to “quickly complete all preclinical studies and move into clinic“. As most us know, hair related research and clinical trial funding are never even a remote priority for governments, universities or scientific institutions. If any of the readers of this blog is super wealthy, maybe give away $1 million to Dr. Terskikh to speed things up for all of us.

Donald Trump’s somewhat crazy (but still believable) long-time physician Dr. Harold Bornstein just claimed to the New York Times in several interviews that both Mr. Trump and Mr. Bornstein take Finasteride to tackle their hair loss problems. Mr. Bornstein claims that his own full head of hair as well as Mr. Trump’s full head of hair are a testament to the efficacy of Finasteride. Surprisingly, the article even mentions how Donald Trump’s prostate specific-antigen (PSA) levels were an extremely low 0.15 due to his taking Finasteride (a hair loss drug that was was originally developed to shrink enlarged prostates in men and in the process reduce PSA levels).

I try not to devote entire posts to celebrity news, but this particular development was significant enough to write about separately. It is very rare to see a story on Finasteride and hair loss in a major newspaper (except when it involves athletes who take the drug and get banned).

Mr. Trump almost certainly has had significant work done to cover his hair loss over the years according to numerous sources. The most in depth research and speculation covering that subject was in this impressive article from last year.

I hope one of Mr. Trump’s advisers tells him about Dutasteride in the near future. Perhaps he can then even get that drug finally approved in the US to treat hair loss. Especially considering this new initiative from the president.

I have always assumed that Replicel probably gets a ton more questions on social media about its hair loss related work versus its tendon repair and skin generation related work. Nevertheless, I do not think that the company’s CEO Lee Buckler ever addressed us hair loss sufferers directly until today (thanks to commentator “ayush” for posting that link). The main point from the video address by Mr. Buckler –> earliest possible release of the company’s RCH-01 hair loss product is in 2018, and that is predicated upon successful clinical trial results from the company’s much larger Japanese partner Shiseido. I suspect that Mr. Buckler got tired of getting the same question over and over again about when they will release the hair loss product and finally decided to release this latest video. It seems like Replicel’s disagreement with Shiseido from last year is not hurting the two companies’ long-term collaboration.

Replicel and Mr. Buckler have been extremely busy in recent weeks. Just from the past week, you can read and listen to two new interviews from the CEO:

• Replicel CEO podcast interview with James West.
• Replicel CEO podcast interview with Dr. Brian McDonough.

And there was also a detailed favorable report on Replicel in Zacks Investment Research two weeks ago as well a “brokered private placement” of common shares by the company.

Also make sure to read my January 2017 brief items of interest post’s first paragraph for more recent news on Replicel.