Bimatoprost, Allergan, Latisse, Lumigan, Prostamide F2α

Bimatoprost and Hair Growth

25 Comments

It is 2015, so finally a good time to write about Bimatoprost. The main reason for this is that at the end of January 2015, Allergan will end its phase II clinical trials for the use of Bimatoprost for hair loss in humans. It is expected that results will be announced shortly thereafter.

What is Bimatoprost?

Bimatoprost is a synthetic prostamide (= prostaglandin-ethanolamide) analog. It is sometimes mistakenly called a prostaglandin analog, since prostaglandins and prostamides are structurally similar to each other. Bimatoprost is increasingly being used in dermatological applications, including off-label for hair growth and pigment related skin issues.

Prostaglandins were originally named due to the mistaken assumption that they were derived from the prostate gland and its secretions. I have written a number of posts on this blog regarding prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2). PGD2 is especially important when it comes to hair loss. Bimatoprost is a prostamide F2α analog. Latanoprost and Travoprost are examples of prostaglandin F2α analogs.

Current Uses

While approval for use to grow scalp hair will depend on the upcoming phase 2 clinical trial results (and hopefully Allergan will decide to fund further phase 3 clinical trials), Bimatoprost has already been FDA approved for use in humans for:

  1. Glaucoma and ocular hypertension treatment, approval in 2001 (brand name Lumigan). Dosage = 1 drop of Lumigan 0.01 percent or Lumigan 0.03 percent depending on source, once daily.
  2. Eyelash growth (lengthening) treatment, approval in 2008 (brand name Latisse). Dosage = 1 drop of Latisse 0.03 percent, once daily.

Bimatoprost Side Effects

Although there are some significant side effects (e.g., darkening of iris, undereye, eyelash and eyelid), that can occur when using Bimatoprost for the above applications, most seem to be reversible.

It is also great to know that people have been using this product in such a sensitive areas as the eye for over a decade now without any large-scale reports of major injuries, nor any class action lawsuits against Allergan.

Will Bimatoprost be a Miracle Treatment for Hair Loss?

Initially when I first read about Bimatoprost a few years ago, I felt that it was going to be inferior to Minoxidil and not worth researching. For one, eyelash growth type results on scalp hair would be a joke in my opinion. More significantly, I thought that all Bimatoprost was doing was keeping scalp hair in anagen (growth) phase for a longer duration.

So once the androgens and dihydrotestosterone (DHT) killed the scalp hair, Bimatoprost would no longer have any positive effect. So my feeling was that all you were getting was a temporary spike in the amount of your hair that was in anagen phase. Also implying lengthier hair for a short time.

However, I have started to doubt my initial skepticism about this product. In 2013 Dr. Valerie Randall and a number of other co-authors published a great study on the successful use of Bimatoprost to grow human hair (in organ culture) and mouse hair (in vivo). The most interesting aspect of the study was that it seems like Bimatoprost stimulates intercellular signaling pathways and causes keratinocytes to produce increased hair growth as well as melanocytes to produce increased pigmentation. The whole process seems to start in the dermal papilla (which ties in to my recent posts on the University of Calgary’s and Replicel’s work related to dermal sheath cup cells).

It seems like Bimatoprost is not just temporarily keeping scalp hair in anagen phase longer. It is actually altering scalp biology at the cellular level and changing paracrine signaling (cell to cell communication) that may end up increasing protection against the ravages of DHT. According to the study:

Bimatoprost caused individual isolated scalp hair follicles from 10 different people to stay in anagen longer in organ culture, and about one-third more new hair was synthesized over 9 d with 100 and 1000 nM.

Note that the 100nM and 1000nM are dose measures, and much higher than the 0.03% present in Latisse and Lumigan. Another part of the study concludes that results from 100nM were better than from 10nM, but results from 1000nM were essentially the same as from 100nM. This is kind of the same phenomenon that we see in studies that show the negligible gains from higher and higher doses of Finasteride or Dutasteride.

My feeling is that Bimatoprost may result in slightly superior results to Minoxidil, but nothing extraordinary. Will this be sufficient for Allergan to fund final stage 3 clinical trials? I would hope so, considering how well the company has done recently.

Hair Follicle Stem Cells, Macrophages, Wnt/Beta-Catenin

Macrophages and Hair Follicle Stem Cells

11 Comments

Update: Seems like the positive impact of macrophages on hair growth was already known in 2007. That study from Japan was titled “Macrophages boost hair growth.” Thanks to commenter “spain”.

I heard about all of the above developments right around when they first occurred. Nevertheless, I was still not particularly hopeful of anything significant happening in Spain when it comes to hair loss research related breakthroughs. Most of the widely respected hair loss research scientists in the world seem to reside in the US, UK, Germany, Japan and several other parts of Northern Europe and East Asia.

Macrophages and the Activation of Hair Follicle Stem Cells

However, two days ago, Spanish scientists (from the previously mentioned cancer research institute CNIO) led by Dr. Mirna Perez-Moreno and Dr. Donatello Castellana published a groundbreaking hair loss research related paper in the PLOS Biology journal titled “Macrophages contribute to the cyclic activation of adult hair follicle stem cells.” It should be noted that Dr. Moreno has previously worked at noted hair loss researcher Elaine Fuchs’ laboratory as a postdoctoral fellow. Further lending credibility to this paper is a third co-author and well known hair loss researcher by the name of Dr. Ralf Paus.

For the average layperson (including myself), the above publication is difficult to digest in its entirety. At least if one does not want to spend hours reading it and going back and forth with google dictionary. So below are links to articles with easier to understand summaries:

Article 1: From the sometimes great, usually trashy DailyMail.

Article 2: From the Spanish elpais (use the “Translate to English” option in the Chrome browser).

The main findings:

  1. Macrophages (a type of white blood cell) can activate adult hair follicle stem cells.
  2. Mice started to regrow hair when they were given anti-inflammatory drugs. It seems like this whole year in hair loss research can largely be summed up by the words “inflammation” and “anti-inflammatory”.
  3.  Macrophages secrete a number of growth factors including a class of proteins called Wnt. You can do a search on this blog for Wnt, Wnt7b and Wnt/Beta-Catenin to learn more about Wnt proteins and corresponding pathways.

As usual the study was carried out in mice and not humans. However, I think that it is now only a matter of a short time before we see an increasing number of trials in humans. As I have mentioned many times, this will probably happen faster in Asia than in other regions due to regulatory reasons.