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Getting to the root of hair loss

Although male pattern baldness is not a disease, many men would like to see it "cured." And many women who suffer from the type of hair loss known as alopecia areata would like to have an effective treatment for it. Unfortunately, not much can be done about these conditions since their cause remains obscure. Now, however, thanks to the work of a woman who has struggled with alopecia herself, scientists are uncovering the genetic roots of both types of hair loss, and the discoveries may lead to hair-preserving therapies — someday.

Angela Christiano, a professor of dermatology and genetics at Columbia University Medical Center, is the lead author of two recent papers in the prestigious journal Nature. One paper involves a genetic study that may have implications for male pattern baldness. The other has found an intriguing genetic clue to alopecia areata.

In the paper published in the April 15 issue of Nature, Christiano studied two Pakistani families and one Italian family whose members have inherited hypotrichosis simplex, a rare disorder that affects hair follicles in the same way as common male pattern baldness.

The people with hypotrichosis simplex have a mutation in a gene that has been linked to other forms of hair loss. The gene has been known to inhibit a cell-signaling pathway known as Wnt. The pathway has been shown to control the growth of hair in mice, but it was never suspected of being involved in human hair loss.

"If you activate that pathway in mice, they grow more hair, and if you inhibit it, they grow less hair," Christiano said. "We can grow hair on a mouse — we can do a lot for mice — but our paper marked the first time the Wnt pathway was implicated in hair loss in humans."

Male pattern baldness, like hypotrichosis simplex, doesn't involve actual loss of hair. Rather, in both disorders the hair follicle shrinks dramatically, and the hair shaft that emerges from it becomes so thin and pale that it's almost invisible, like the downy strands known as vellus hairs found on the cheeks and other seemingly "hairless" areas. The hair follicle remains healthy — it just undergoes a process of miniaturization that causes it to produces much smaller hairs.

"It's as though the follicle has been put through the reduce function on a photocopier," Christiano said. "The follicle is the same but proportionately smaller. That process of miniaturization is key feature of both male pattern baldness and hypotrichosis simplex. The hair follicle undergoes the same change in both."

The discovery provides a vital clue to those who would like to develop a treatment for male pattern baldness that works better than the hormone inhibitors currently available, such as Propecia, but no one appears to be pursuing the clue yet.

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Alopecia areata is an autoimmune disorder in which the immune system decides, for reasons no one understands, that hair follicles are foreign objects, like bacteria and viruses, and must be destroyed.

Christiano herself developed this disorder in 1996, when her hairdresser noticed a bald spot about the diameter of a soup can on the back of her head. She eventually developed 10 such patches and, over time, doctors treated each with steroid injections to suppress the autoimmune attack.

The disease appears to be in remission, and Christiano currently sports lush locks, but she is concerned that there could be a relapse. Although she acknowledges that alopecia areata takes its largest toll on a person's vanity, she decided to investigate the disorder when she discovered it affects more than 5 million Americans.

As reported in the July 1 issue of Nature, Christiano and her colleagues have uncovered eight genes implicated in alopecia. Of the eight genes, one stands out — a gene called ULBP3, which provides instructions for a protein that flags tissues for destruction by the immune system. This provides a tantalizing clue not just to alopecia areata, but to such devastating diseases as rheumatoid arthritis, Type 1 diabetes and celiac disease.

"One thing common among autoimmune diseases is that there's a danger signal expressed in the organ — the pancreas, a joint, a hair follicle — that actually serves as a homing beacon for certain types of immune cells to come in and attack," Christiano said. "Like bees going to nectar, the immune system's killer cells are very attracted to that signal. In alopecia areata, the killer cells go in, damage hair follicles, and trigger an immune response that doesn't know how to shut itself off. That's what leads to autoimmunity."

Christiano identified the genes by examining more than 1,000 samples from the National Alopecia Areata Registry. By comparing the samples to people free of the disease, she and her colleagues were able to identify genes that always seem to be present at the scene of the crime.

The discovery may lead to new treatments for alopecia areata, Christiano said, although she herself is not pursuing any.

"Treatment is a ways off," she said.

Tom Valeo writes frequently about health matters. He can be reached at tom.valeo@gmail.com.

Getting to the root of hair loss 08/24/10 [Last modified: Monday, August 23, 2010 7:37pm]
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