A Review of Advances In Understanding & Treating Male & Female Androgenetic Alopecia

by Robert Bernstein, MD

In a recent (2014) literature review, “Regenerative Medicine And Hair Loss: How Hair Follicle Culture Has Advanced Our Understanding Of Treatment Options For Androgenetic Alopecia” (Regen Med. 2014 Jan;9(1):101-11), Dr. Claire Higgins and Dr. Angela Christiano, both in the Department of Dermatology at Columbia University, reveal how current culture techniques are leading to better treatment options for male and female patient with androgenetic alopecia type hair loss.

What is Androgenetic Alopecia?

Androgenetic alopecia is a hereditary disease where a hormone called dihydrotestosterone (DHT) acts on genetically-susceptible scalp hair follicles in two ways:

  1. Susceptible hair follicles enter into progressively longer periods of their telogen (resting) phase relative to their anagen (hair growth) phase, and this causes hair shafts to become progressively smaller.
  2. Susceptible hair follicles progressively shrink (miniaturize) producing shorter and finer hairs that eventually disappear altogether.

New Drug Development for Androgenetic Alopecia

Since the early 1990’s, researchers have been able to study isolated hair follicles using cell culture techniques. These techniques have opened the door to better treatment options for androgenetic alopecia by using medications to interrupt the effects of DHT on genetically-susceptible follicles.

For example, hair follicles grown in a serum-free medium supplemented with insulin and hydrocortisone will reliably shift from their growth phase (anagen) to their telogen (resting) phase after a few days; this allows researchers to test new drug biologics to see how effective they are in delaying this shift. Prematurely shifting hair into telogen is one of the ways DHT causes hair loss in androgenetic alopecia; such tests could lead to the development of new and better drugs which interrupt this specific effect of DHT on susceptible follicles.

More recently, researchers have been able to grow intermediate hair follicles to model the miniaturization of genetically-susceptible hair follicles. This could lead to the development of new drugs which effectively interrupt the shrinking of DHT susceptible follicles.

Better Existing Drug Understanding & New Drug Discoveries for Androgenetic Alopecia

Minoxidil is currently the most widely used treatment for both male and female pattern baldness. However, its effectiveness varies from patient to patient. There are two competing hypotheses explaining this variability: minoxidil either works on the microenvironment surrounding the hair follicle by increasing the blood flow surrounding the follicle or it acts directly on the hair follicle to promote hair growth.

Recent research using hair follicle organ cultures supports the latter hypothesis: the best recent evidence indicates that minoxidil acts directly on the follicle by opening ATP sensitive potassium channels within the dermal papilla to both initiate and drive the anagen (growth) phase of the follicle’s hair cycle. This new understanding of minoxidil’s mechanism of action could lead to the discovery of better growth inducing drug biologics that act directly on the follicle.

Finasteride is also a highly successful drug treatment for androgenetic alopecia, but it is only approved for men because of the risk of birth defects in women. Because of this, minoxidil remains currently the only FDA approved treatment for women.

However, in 2010, researchers discovered that a prostamide F2α-related analog called bimatoprost, a drug used to treat glaucoma, caused eyelash growth as a side effect. After discovering prostanoid receptors inside the dermal papilla of hair follicles, researchers used follicle organ cultures to see if bimatoprost could stimulate hair growth. These cultures found that bimatoprost did significantly enhance hair growth.

While clinical trials evaluating bimatoprost in women with female pattern hair loss are currently ongoing, preliminary finding suggest that F2α analogs could become an effective drug treatment.

Neogenesis of Hair Follicle Promises More Widely Available Hair Transplants

It is known that dermal papilla cells taken from existing hair follicles and injected back into the skin can cause the growth of new hair follicles at the site of the injection, a phenomena known as “follicular neogenesis.” Because of this hair inducing capacity, it is logical to assume that by expanding (cloning) dermal papilla cells in culture, one would be able to inject new dermal papilla cells into the frontal or balding part of the scalp where they can then either induce new hair follicle growth or reverse miniaturization of DHT sensitive hair follicles.

Unfortunately, in culture, new dermal papilla cells quickly lose their ability to create new hair follicles. One theory explaining why this happens is that in a petri-dish culture, dermal papilla cells grow flat (i.e. on a two dimensional plane) and are cut off from critical growth signals normally present in their natural 3-D environment.

In a test of this theory, Dr. Angela M. Christiano devised a way to grow dermal papillae cells in a three dimensional culture rather than in a conventional two dimensional tissue culture. She reasoned that if the intrinsic signaling could be restored in such 3-D cultures, the human dermal papilla cells should recover their ability to create new hair follicles. And this is exactly what she found.

According to Dr. Christiano, this discovery represents a major breakthrough in being able to create new follicles, rather than merely moving a limited number of existing follicles from one part of the scalp to another (as is currently done in hair transplantation).

Being able to induce new human hair growth from cloned human papillae could significantly expand the use of hair transplantation to women with hair loss, who tend to have insufficient donor hair, as well as to men in early stages of baldness.

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