One of the leading pioneers in researching a stem cell treatment for hair loss, Dr. George Cotsarelis at the University of Pennsylvania’s Perelman Center for Advanced Medicine, just let slip that a new approach to growing new hair could be in the works: A topical cream designed to counteract the effects of a hormone-like substance, known as Prostaglandin D2, that may play a key role in baldness.
In the March 21 issue of Science Translational Medicine, Dr. Cotsarelis reported that his team discovered that Prostaglandin D2 is present in much higher levels in the bald areas of men’s scalp but not present in the hairier areas, such as on the side of the head. Dr. Cotsarelis’s team previously discovered that stem cells in hair follicles are not “dead,” as previously thought, but only dormant… and that something is preventing them from turning into the “progenitor cells” that actually produce hair.
In the past, medical researchers theorized that baldness is due to a genetic hypersensitivity to dihydrotestosterone (DHT). This potent sex hormone is a derivative of testosterone, made by the body with the help of an enzyme, 5-alpha-reductase. In addition to playing a major role in prostate enlargement, DHT also, in some men and women, triggers a miniaturization of the hair follicles in certain areas, causing a gradual thinning of the hair until the follicle ceases to produce any hair at all. One method of treating this is topical creams that remove excess DHT from the scalp. Another is through the prescription drug finasteride (Propecia), originally used to treat enlarged prostates. This drug is known as a 5-alpha-reductase inhibitor because it “inhibits” the action of the enzyme that produces DHT, thus reducing the amount of DHT in someone’s system… and that, in turn, can slow down and even reverse hair loss. Finasteride is effective about 50% of the time, but it comes with some risks: Recent studies warn that it may cause impotence, decreased sex drive and depression.
Now, Dr. Cotsaerlis’s team has thrown another complicating factor into the mix: Prostaglandin D2. The question they were confronting was: What causes the stem cells in hair follicles to become dormant? Is it the lack of something (growth stimuli) or the presence of something (an inhibitor)?
The team analyzed scalp tissue from men undergoing hair transplant surgeries. They discovered no fewer than 81 different genes with higher activity in the balding areas of the scalp compared to the hairier areas, and one of these genes produced Prostaglandin D2. The researchers concluded, therefore, that it was the presence of something, Prostaglandin D2, that was holding back hair growth. (To further complicate matters, however — nothing in science is ever simple — they discovered another prostaglandin, F2alpha, that appears to stimulate the growth of eyelashes.) The researchers tested their hypothesis in the lab with human hair follicles and on bald mice and, sure enough, Prostaglandin D2 definitely caused baldness when they applied it to skin.
Digging deeper, the researchers found that Prostaglandin D2 works on stem cells in combination with another protein, GPR44, which triggers a “biochemical chain reaction” when it encounters Prostaglandin D2. It might be possible, therefore, to develop a drug or cream that eliminates this other protein, GPR44, which renders Prostaglandin D harmless to stem cells in hair follicles.
Further proof that the scientists may be on the right track can be seen by the fact that Minoxidil — along with finasteride one of two drugs approved by the FDA for hair growth — activates an enzyme that produces… yes, you guessed it… prostaglandins!
So, where does all this leave us? What happened to DHT? The scientists’ best guess now is that hair growth is caused by a delicate balance of prostagladins. Prostaglandins are chemical messengers made from fatty acids, similar to hormones, present in every cell in the body. There are at least 16 different major types. It may well turn out that the old medical understanding of what causes baldness — a hypersensitivity to DHT — was correct but just too simplistic. In other words, it may be that what causes hair loss is an imbalance of prostaglandins — too much of one, not enough of another — and that all we have to do is restore that balance and voila! instance hair growth!
The creation in 1997 of a prostaglandin analog, latanoprost, and the subsequent discovery that it stimulates new hair growth in eyelashes, lends some credence to this theory.
Nevertheless, science proceeds at a snail’s pace and everyone associated with this research urges caution. As Yogi Berra put it, “it’s tough to make predictions, especially about the future.”
Dr. Cotsarelis told the BBC recently that the next step in his research is to search for compounds that have an effect on the “receptor” in the stem cells — presumably GPR44 — and then to figure out if blocking this receptor would merely prevent hair loss or could actually reverse it. However, he added that there are “several” drugs already in existence that target this “pathway” and that clinical trials are already underway.
Maddening, isn’t it? They seem to be inching closer and closer to understanding the biochemical basis for hair loss yet remain very far from having a practical, real-world treatment.
Yet we are much closer than we were even just a few years ago. You know what they say: growing old beats the alternative… a learning a little beats learning nothing.