By Mia Schmiedeskamp
Drug companies are busy searching for the next generation of hair-promoting compounds

FEW PEOPLE ACCEPT hair loss with equanimity. "People often say to me they can deal with the loss of a kidney…but not with hair loss", says Vera H. Price, director of the Hair Research Center at the University of California at San Francisco. So how can science help?
The good biological news is that in the most common types of thinning, hair follicles don't die. In classic male-and female-pattern hair loss (androgenetic alopecia), for instance, follicles become miniaturized and growing phases abbreviated; they then produce extremely short, fine hairs, " Even guys who are bald still have little hairs on the top of their head," explains Bruce A. Morgan of Harvard's Cutaneous Biology Research Center. In a rarer condition, alopecia areata (affecting nearly 2 percent of people), the follicles' growth phase ends prematurely under autoimmune attack, causing hair to fall out in patches or, in extreme cases, all over the body. But, again, the follicles survive.
Treatment for alopecia areata typically focuses on quelling the wayward immune system, but treatment for male-and female-pattern hair loss must increase the size of Lilliputian follicles as well as hair length. Minoxidil-introduced as Rogaine in 1988-was the first drug approved by the U.S. Food and Drug Administration for this purpose and is the only licensed for use in both sexes. Scientists still debate how minoxidil, which is applied topically, produces thicker, longer hairs: perhaps it increases blood supply, better nourishing the follicles, or perhaps it alters cellular concentrations of substances that regulate hair growth.
The mechanism of the second approved drug, finasteride, is clearer. This compound, marketed as Propecia for male hair loss(and as Proscar in a higher-dose formulations for prostate enlargement) is taken orally. In the body, it inhibits an enzyme that converts testosterone to a hormone called dihydrotestosterone (DHT) and thus reduces DHT production. DHT is critical to the development of male fetuses, but later it can be a troublemaker. It stimulates some follicles to produce thick, long hair (on the cheek and chin, for example), and it induces scalp hair thinning in susceptible people, sometimes as early as the preteen years. Some researchers suspect that DHT disrupts hair follicles by acting on a region called the dermal papilla, altering its production of substances that influence hair growth.
In a study published in 1998 or more than 1,200 men between the ages of 18 and 41 with mild to moderate hair loss, about 83 percent maintained the hair they had on the top of their head after two years of finasteride use. More than half had at least mild regrowth. But Jerry Shapiro, director of the University of British Columbia Hair Research and Treatment Center, cautions, "I think the big job is to keep patients' expectation levels appropriate, so that they know it's not going to be luxuriant hair. The emphasis should be on prevention. Regrowth is also a possibility but shouldn't be stressed, especially in men with more advanced hair loss."
Men can expect similar results with 5 percent minoxidil, advises Marty E. Sawaya of ARATEC, which conducts clinical trials for various companies. She estimates that 25 to 30 percent of men gain moderate-to-dense regrowth with either product. Some men hedge their bets by using both over-the-counter minoxidil and prescription finasteride. In stumptailed macaques, at least, the two drugs together worked better than either one alone.
Shapiro and Price advise their patients to allow about a year to see whether hair-growth drugs work-and to commit to using them correctly. Minoxidil solution is applied directly to the scalp twice daily; Propecia is a once-daily pill. To maintain results, either drug must be used consistently and indefinitely. "Nothing reverses thinning completely, " Price says. "But do these drugs work? Yes, they work."
For remaile-patter hair loss, only 2 percent minoxidil has FDA approval. About 60 percent of woman achieve maintenance of hair and some regrowth with this option. Those with the opposite woe of unwanted facial hair now have an FDA-approved option, too; topical eflornithine cream, marketing as Vaniqa, inhibits an enzyme necessary for cell proliferation, thus retarding hair growth. But experts once more caution patients to keep their expectations reasonable. About 58 percent of women see slight improvement or better, usually after a couple of months. The cream slows hair growth but does not stop it, so treated women do continue to tweeze or remove hairs by other means.

Looking Ahead
MUCH RESEARCH done by companies is kept secret until drug candidates reach clinical trials. Probably, though, the next hair-loss treatments to come down the road will work on familiar principles.

"THIS IS A WONDERFUL TIME TO BE WORKING IN HAIR BIOLOGY. SO MANY BREAKTHROUGHS ARE COMING."
--Kurt S. Stenn, Juvenir Biosciences

Several companies have developed molecules that inhibit the same enzyme as finasteride. Hoechst AG has done some laboratory testing of a drug that would be applied to the scalp to block DHT from binding to hair follicle cells. And Bristol-Myers Squibb has a drug in early clinical studies that is thought to function similarly to minoxidil.
Perhaps the most promising compound to enter human trials is called dutasteride, from GlaxoSmithKlien. Like finasteride, it inhibits the enzyme that produces DHT, but it blocks two forms of the enzyme instead of just one. Sawaya says the preliminary results suggest that dutasteride is more effective at increasing hair count than finasteride, even at a lower dose.
"We don't have a product yet that's going to be 'wow!' for over 50 percent of people," she notes, "I do think dusateride will be that product if the company goes forward." When or if FDA approval might be sought for using dutasteride against hair loss remains uncertain, however. Gaining approvals is time-consuming and costly, and GlaxoSmithKlien may choose to pursue it first as a prostate drug, as happened with finasteride.
Scientists are on the prowl for new drugs all the time. Morgan's Harvard colleague Michael Detmar discovered earlier this year that abundant amounts of a growth factor that increases the blood supply make mice grow hair faster and thicker. Now, Morgan says, the hunt is on for small molecules that will wither mimic or activate the factor. But drugs like that or ones intended to interact with molecules that directly regulate hair growth-such as Wnt or beta-catenin- are a long way off. Much more research needs to be done before the right targets can be manipulated without risking such consequences as cancer.
A fundamental understanding of hair biology may someday let physicians replace a defective gene in hair follicles through gene therapy or grow hairs in a petri dish for use in graft surgery. " The complexity of the question is like understanding how a limb forms. It's ambitious. But we are discovering a lot and discovering a lot quickly," muses Kurt S. Stenn, chief scientific officer of Juvenir Biosciences, a company recently spun off from Johnson & Johnson to focus predominantely on hair research. "This is a wonderful time to be working in hair biology. So many breakthroughs are coming."
Mia Schmiedeskamp is a science writer based in Seattle.