The Wall Street Journal
By SHIRLEY S. WANG
Several research teams are working to figure out ways to spur existing follicles—the tiny organs in the skin that give birth to hair—back into action, or to make new, active follicles. New treatments based on this work likely are many years from the market, but these approaches could lead to the significant breakthrough of helping people who are already bald. By contrast, topical products available now, such as Rogaine, appear to be most effective in helping prevent further balding after it has started. And with current surgical procedures, healthy hairs can be moved into bald areas, but if they don’t take, the operation might have to be repeated.
Crucial to the hair-growth and balding process, scientists have found, are vitamin D and the microscopic receptors that bind to it in skin. These elements have become the focus for several research teams. (Supplements might offer health benefits for people lacking enough vitamin D, but they won’t bring back lost hair, researchers say.)
Some researchers, including those from the San Francisco Veterans Affairs Medical Center and Harvard Medical School, have identified molecules besides vitamin D that appear to activate the receptor and hold potential for future treatments. In July, Japanese researchers demonstrated in animals that adding vitamin D helped the process of using stem cells to generate new follicles.
Vitamin D has long been known to be important for keeping bones and skin healthy. But research on its role in bone development has progressed much faster than has the research on skin and hair.
The vitamin D receptor is “crucial for the regeneration of hair,” wrote Mark Haussler, a professor of basic medical sciences at the University of Arizona College of Medicine in Phoenix, in a recent paper. He discovered the receptor in 1969.
Hair growth follows a cycle, with follicles typically producing hair for two to six years before the hair falls out and the follicle lies dormant for a period thought to vary from a few weeks to a few months. A replacement hair then emerges. At any point in time, some 15% of our follicles are sleeping, say researchers.
But for some people, this sleeping phase is permanent, and if enough follicles hibernate in the same skin area, baldness results. The message to grow hair appears to be guided by partner cells called dermal papilla cells. Stem cells in the skin that haven’t matured yet can become regular skin cells or differentiate into hair follicles. Without the right chemical communication, existing follicles go dormant and stem cells that have yet to differentiate themselves may become skin cells instead of follicles.
Many scientists and several companies have tried to expand the number of follicles and normal dermal papilla cells while maintaining their functioning, but have failed.
The demand for better hair-loss treatments is great. Nearly $2 billion a year is spent world-wide in surgical procedures for hair loss, according to the International Society of Hair Restoration Surgery. One of the most common forms of baldness, called androgenetic alopecia—widely known as male-pattern baldness—affects 35 million men in the U.S., according to government data, and is related to the amount of certain hormones in the body. Estimates suggest 20 million to 30 million women also have alopecia, but they generally don’t lose hair in a pattern like men do.
Chemotherapy-induced hair loss in cancer patients is also common, and in some cases, the follicles may die. Several other factors such as childbirth, crash diets and some medications can also lead to hair loss, though the exact reasons why follicles are lulled to sleep isn’t well understood.
Current treatment options include products such as Rogaine and Propecia, which work best for prevention, says Rashid Rashid, a dermatologist at the Mosaic Hair Transplant Center in Houston. Hair transplants—when hairs are moved from one area of the scalp to a bald area—are the other main option. This can be done more quickly than ever now, says Dr. Rashid, but the new hairs fall out after a couple of months and might not regenerate.
Hair-regeneration research poses several challenges, researchers say. Follicles don’t grow hair very well outside the body, so even though the cells can be grown in dishes in a lab, they don’t tend to produce hair.
Much of the research in the field is focused on vitamin D. The receptor—the lock to which the vitamin D key binds—activates hair growth, rather than the vitamin itself, says Marie Demay, a professor of medicine at Harvard Medical School, who pioneered much of this work.
Biochemist Yuko Oda and a team at the VA Medical Center San Francisco and the University of California, San Francisco, recently found a molecule, called MED, that appears to suppress the actions of the receptor. In a study published in December in the Journal of Investigative Dermatology, they found that mice grew less hair after the gene that codes for MED in their skin was knocked out, suggesting a target for gene therapy.
Dr. Demay and colleagues last year found another molecule called LEF1 that also activates the vitamin D receptor, and can do so without the presence of vitamin D. The next step will be to demonstrate that activating the receptor in this way would actually produce hair, says Dr. Demay. If these molecules activate the vitamin D receptor, they change the “fate” of the cells into hair cells, Dr. Oda says. The work was published in the Journal of Biological Chemistry.
Researchers at the University of Tokyo recently added vitamin D supplements to the medium in which they were growing dermal papilla cells, hoping to spur more uncommitted stem cells to become active follicles.
In rats, the scientists found more stem cells were coaxed into becoming follicles when vitamin D was used in the final phase of growing the cells than those not treated, says Kotaro Yoshimura, a professor in the department of plastic surgery who was the senior author on the paper. In addition, more of those follicles matured to produce hair, raising the hope that this might lead to improved hair transplants in the future. The study appeared in the journal Stem Cells Translational Medicine.
Currently, hair transplants can only get single hair from one follicle “but we want to make 1,000 hairs from one follicle,” one after the next, says Dr. Yoshimura. They are now teaming up with two other sets of researchers and planning a clinical trial.
A challenge for researchers is that vitamin D has many functions in the body, such as improving bone growth. Taking too much vitamin D can have negative side effects such as calcium accumulation in the blood causing weakness or kidney problems, according to the Mayo Clinic. So it is important that any potential treatment be finely targeted. “We’re really aiming to manipulate vitamin D or vitamin D receptors only in the skin,” Dr. Oda says.
However, the majority of Americans don’t get the recommended daily dose of the vitamin. For some, getting their full amount—from foods such as fatty fish or from being in the sun—may generally improve health and aid hair growth, Dr Haussler says.
Corrections & Amplifications
Mice grew less hair after a gene that codes for a molecule called MED in their skin was knocked out in an experiment. An earlier version of this article incorrectly said that knocking out the gene led to more hair growth. Also, an earlier version of this article incorrectly said hair transplants need to be continuously repeated and that transplanted hairs don’t regenerate. In addition, an earlier version said Mark Haussler was a professor in physiology, chemistry and biochemistry at Arizona State University in Phoenix; and Propecia was incorrectly described as a topical treatment.