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Is the end of the shiny head in sight, or are there no shoots of hope for a treatment? Daniel Cossins investigates.
Nothing reminds a man of his mortality more than a retreating hairline or the peach-fuzz feel of his thinning crown. For men entering middle age, effective ways to avoid hair loss can’t come soon enough. But balding has long proved a slippery foe for scientists. Despite decades of research, the fundamental biological mechanisms underlying it are not well understood. The question is whether there are any signs that this will change.
“For a long time there was a hiatus in term of coming up with new ideas,” says Angela Christiano of Columbia University in New York. “But right now is a really exciting time for the field.”
We have been pondering the causes of male-pattern baldness, also known as androgenetic alopecia, for centuries. The Greek philosopher Aristotle noticed that eunuchs don’t go bald. We now know this is because a by-product of the hormone testosterone – produced in the testicles – called DHT gradually shrinks hair follicles in the scalp, reducing the length and thickness of the fibers produced until they no longer breach the surface of the skin. Unfortunately, we don’t know much more than that.
There are hair loss treatments that have been approved by the US Food and Drug Administration, such as finasteride (Propecia) and minoxidil (Rogaine), which can prevent or slow hair loss in some men. Their virtues were discovered serendipitously, as side effects of drugs developed for other ailments. But right now there are no drugs that can reverse hair loss. To do that you need a hair transplant, an expensive and gorily invasive procedure in which fully functional follicles from the back of the scalp are relocated to desolate patches elsewhere.
The biology behind baldess may be complex, but the last few years has seen what could be described as hair-raising progress. In 2012, Luis Garza of Johns Hopkins University in Baltimore and colleagues discovered that a lipid compound called Prostaglandin D2 (PGD2) plays a key role in squeezing the life out of follicles. Gene expression analysis showed that PGD2 and the enzyme that makes it were far more abundant in balding than non-balding scalps. Most importantly, when the researchers added PGD2 to human follicles in a petri dish, hair growth was dramatically reduced.
The team also pinpointed the receptor on follicle cells to which PGD2 attaches to do its dastardly deed. In mice without the receptor, known as GPR44, PGD2 did not restrain hair growth. If the same is true in humans and we can figure out how to interrupt this mechanism – by either blocking the receptor or disabling the enzyme that makes PGD2 – we could put the brakes on hair loss. “We now have a very good target,” says Garza.
Drug promise
Conveniently enough, pharmaceutical companies are already testing drugs designed to block GPR44, as this has been implicated in allergic conditions such as asthma. That’s a great place to start, says Garza. But even if an existing compound blocks the version of the receptor on follicle cells and stops hair loss in lab-cultured follicles, the path to human trials is long and expensive.
What’s more, the PGD2 receptor may not be working alone. Instead, it may be just one of several agents that trigger follicle regression and it’s possible that it plays only a minor role. We won’t know how central PGD2’s role is until a treatment based on it is tested properly in humans because there are no animal models of male pattern baldness. “It’s got to be worth trying,” says Garza, “because a treatment for baldness that really worked would be an enormous blockbuster.”
Nothing reminds a man of his mortality more than a retreating hairline or the peach-fuzz feel of his thinning crown. For men entering middle age, effective ways to avoid hair loss can’t come soon enough. But balding has long proved a slippery foe for scientists. Despite decades of research, the fundamental biological mechanisms underlying it are not well understood. The question is whether there are any signs that this will change.
“For a long time there was a hiatus in term of coming up with new ideas,” says Angela Christiano of Columbia University in New York. “But right now is a really exciting time for the field.”
We have been pondering the causes of male-pattern baldness, also known as androgenetic alopecia, for centuries. The Greek philosopher Aristotle noticed that eunuchs don’t go bald. We now know this is because a by-product of the hormone testosterone – produced in the testicles – called DHT gradually shrinks hair follicles in the scalp, reducing the length and thickness of the fibers produced until they no longer breach the surface of the skin. Unfortunately, we don’t know much more than that.
There are hair loss treatments that have been approved by the US Food and Drug Administration, such as finasteride (Propecia) and minoxidil (Rogaine), which can prevent or slow hair loss in some men. Their virtues were discovered serendipitously, as side effects of drugs developed for other ailments. But right now there are no drugs that can reverse hair loss. To do that you need a hair transplant, an expensive and gorily invasive procedure in which fully functional follicles from the back of the scalp are relocated to desolate patches elsewhere.
The biology behind baldess may be complex, but the last few years has seen what could be described as hair-raising progress. In 2012, Luis Garza of Johns Hopkins University in Baltimore and colleagues discovered that a lipid compound called Prostaglandin D2 (PGD2) plays a key role in squeezing the life out of follicles. Gene expression analysis showed that PGD2 and the enzyme that makes it were far more abundant in balding than non-balding scalps. Most importantly, when the researchers added PGD2 to human follicles in a petri dish, hair growth was dramatically reduced.
The team also pinpointed the receptor on follicle cells to which PGD2 attaches to do its dastardly deed. In mice without the receptor, known as GPR44, PGD2 did not restrain hair growth. If the same is true in humans and we can figure out how to interrupt this mechanism – by either blocking the receptor or disabling the enzyme that makes PGD2 – we could put the brakes on hair loss. “We now have a very good target,” says Garza.
Drug promise
Conveniently enough, pharmaceutical companies are already testing drugs designed to block GPR44, as this has been implicated in allergic conditions such as asthma. That’s a great place to start, says Garza. But even if an existing compound blocks the version of the receptor on follicle cells and stops hair loss in lab-cultured follicles, the path to human trials is long and expensive.
What’s more, the PGD2 receptor may not be working alone. Instead, it may be just one of several agents that trigger follicle regression and it’s possible that it plays only a minor role. We won’t know how central PGD2’s role is until a treatment based on it is tested properly in humans because there are no animal models of male pattern baldness. “It’s got to be worth trying,” says Garza, “because a treatment for baldness that really worked would be an enormous blockbuster.” |
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发表于 2013-11-27 22:40:17
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发表于 2013-11-28 09:11:07
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