Cyclosporine for Hair Loss Revisited

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 Alopecia1990 (Israel — from the prestigious Technion University). The now deceased forum member Bryan pasted the whole study for is on HLH2 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“.

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.

Tricopigmentation: A Temporary Form of Scalp Micropigmentation

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.

PRP Free Treatment Session(s) Winner Selection

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

After the second and final random number generation, the winner and runner-up are as follows:

Winner = “Robb”

Runner-up = “Emperor Alopecia”

Ironically, the person who is located furthest away from Dr. Rapaport’s New Jersey office won! In the event that Robb does not make it or if Dr. Rapaport has issues with scheduling and decides against accepting someone from outside the US (unlikely), Emperor Alopecia will take Robb’s place.

I hate rejecting people who are in the final five, but unfortunately I have to do the prize drawings in this manner for now.  I need to get a few names in the second round drawing in the event that one or more are suspicious entries, change their mind, do not e-mail me back, or if we need a backup winner in cases such as this unusual multiple session PRP treatment prize drawing.

Robb, I will send your contact information to Dr. Rapaport’s office. If you do not hear from them by early next week, please let me know.

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.

A Hair Loss Blog