Taking Control

Getting Beneath the Surface

What's new in scientifically proven skin-care products? Not much -- yet.

By RHONDA L. RUNDLE

March 20, 2006; Page R7

It isn't easy, it turns out, to come up with a new wrinkle in cosmetic drugs.

The convergence of dermatology and cosmetics, spurred by the success of antiwrinkle drugs like Botox, is fueling consumer demand for new skin-care treatments. But the marketplace is still thin on scientifically proven products.

There is a lot of promising research proceeding in the areas of cell repair, tissue regeneration and wound healing that may eventually have cosmetic applications. Scientists are working toward an understanding of the aging process for skin, searching for clues that will help them develop collagens and elastins for facial rejuvenation, among other treatments. They are studying both the human genome, in hopes of developing personalized skin-care treatments, and the genomes of agents that cause skin diseases, to better understand how to attack those ailments.

But progress has been agonizingly slow. Knowledge of the molecular biology of skin lags behind that for some other parts of the body, partly because the aging of the skin is uniquely affected by exposure to the sun and the elements. For now, "all of the fixes we're talking about are temporary and don't reflect understanding of the aging process," says David J. Leffell, professor of dermatology at the Yale University School of Medicine. And while a handful of small commercial ventures are formulating customized skin-care regimens for consumers who first pay for a genetic test performed on a cheek swab, scientists generally say the information derived from such tests isn't complete enough to be meaningful.

Over the Counter

Meanwhile, more dermatologists and cosmetics companies are joining forces to market so-called cosmeceuticals -- over-the-counter cosmetic products backed by scientific research that falls short of the standards for the approval of drugs by the Food and Drug Administration.

For those who are pursuing FDA approval, some research has moved beyond the laboratory and into human tests. AGI Dermatics, a closely held company in Freeport, N.Y., is testing a lotion called Dimericine for patients with a rare genetic disease that predisposes them to skin cancer. If the drug works to prevent skin cancer, it could have broader application as a skin-repair agent. At the same time, a small publicly traded Pennsylvania company, Isolagen Inc., is injecting a patient's own cultured skin cells into frown lines and wrinkles in an effort to restore collagen to the sagging face.

Dimericine lotion contains an enzyme that has been shown to repair damaged DNA in laboratory studies. But the challenge for scientists has long been to find ways that would allow such topical treatments to penetrate the skin and work at the cellular level. AGI Dermatics says Dimericine works by delivering the gene-altering enzyme into living skin cells using microscopic lipid sacs called liposomes.

In 2001, nine years after its initial filing with the FDA, AGI Dermatics finished a test of 30 patients who suffer from xeroderma pigmentosum, a disease that leaves people susceptible to skin cancer. The lotion lowered the rate of actinic keratoses (lesions resulting from overexposure to the sun that can develop into skin cancer) and basal-cell carcinomas (the most common type of skin cancer) by 68% and 30%, respectively, during a year of treatment, according to results published in the Lancet, a British medical journal. But the FDA said the study was too small to approve the drug, and asked for a 100-patient study.

That's difficult to do, because of the rarity of the disease, says Daniel B. Yarosh, an inventor of Dimericine who is also president and chairman of AGI Dermatics. Meanwhile, tests of the drug are either under way or on the drawing board for broader applications, including one in skin-cancer survivors who are at high risk for developing a second or third cancer.

"What we envision is that this would be part of a daily routine that would protect people not only from sunburn, but from a substantial amount" of ultraviolet radiation that causes wrinkles and aging of the skin, Dr. Yarosh says. He calls Dimericine a potential "morning-after cream," to underscore the idea that it might work to repair damage after sun exposure.

A Step Back

Isolagen's therapy is designed to rejuvenate skin through injections of collagen-producing cells grown from the patient's own skin. After the process was invented by researchers in the early 1990s, about 1,100 patients were treated before the FDA stepped in and asked for human studies to be performed. Some 100 physicians who had been using it had to stop.

The treatment begins with the removal of a small piece of skin from behind the ear. The tissue is sent to a lab, where growing the new cells, called fibroblasts, takes four to six weeks. The cells are then injected into facial wrinkles in three visits, spaced two weeks apart. The procedure has been performed in Britain for many years, where it is used by some dermatologists to treat acne scars and burns, as well as wrinkles. A burn victim who was successfully treated three years ago was featured last year in a British press report.

In August, however, Isolagen unveiled some disappointing test results. There was tremendous variation among the results at different sites where patients were treated. The company has blamed the discrepancies on varying injection techniques. The cells have to be injected in a different way from Allergan Inc.'s Botox or dermal fillers such as Medicis Pharmaceutical Corp.'s Restylane, says Marie Lindner, Isolagen senior vice president of medical and business affairs. She says the company is working with the FDA to address the injection issue.

Isolagen hopes to submit a filing for FDA approval of a cosmetic application at around this time next year, and is also planning tests to evaluate the technique's effectiveness in treating vocal-cord scars and gum recession.

"The concept has merit, but the company still needs to get appropriate data to convince physicians this is a viable technology," says Jayson T. Bedford, a life-sciences analyst in San Francisco for Canaccord Adams Inc., a financial-services firm. Isolagen also needs to manufacture cells at a cost low enough to make the concept commercially successful, he adds. The treatments, if eventually approved for U.S. commercialization, are likely to be expensive, even by the standards of cosmetic medicine. In the U.K., Isolagen therapy costs thousands of dollars, with the exact amount depending on the extent of treatments. That's significantly more costly than dermal fillers, which generally cost several hundred dollars.

The most popular cosmetic medical treatments, including Allergan's Botox and Johnson & Johnson's Retin-A ® (marchio registrato), were proved effective through rigorous FDA trials. But in the absence of a steady stream of such products, there is a growing market for the over-the-counter products known as cosmeceuticals. New York-based DermaPlus Inc. has developed an antiwrinkle cosmeceutical called DermaLastyl. Burt Ensley, a microbiologist who is the chief executive of DermaPlus, says tests have shown that daily applications of DermaLastyl can prevent the loss of elastin -- the protein that gives skin its elastic quality -- that comes through the normal aging process.

What Works?

The problem for consumers is that there is no accepted standard of proof of effectiveness for cosmeceuticals, says Sheldon R. Pinnell, a founder of the skin-care company SkinCeuticals and a former head of the Duke University School of Medicine's dermatology division. However, he adds, if cosmetics companies publish their research in peer-reviewed journals, independent analysts can evaluate the studies and reproduce them.

Cosmetics companies increasingly are publishing their research, and dermatologists are seeking it out. SkinCeuticals, for instance, says all of its products are backed with published studies. The company, founded in Dallas in 1997, was acquired last year by French cosmetics giant L'Oréal SA.

Many scientists sniff at such efforts, because the research isn't held to the demanding standards of the FDA. But proponents of such products say the rigorous FDA tests are prohibitively expensive.

AGI Dermatics, the company developing Dimericine, has been a supplier of ingredients to cosmetics companies for many years. This month, the company is launching its own line of cosmetics called Remergent. Dr. Yarosh says he hopes to be "a bridge" between the cosmetics and dermatology worlds, partly by publishing studies on active cosmetics ingredients in medical journals that are reviewed by other scientists. The Remergent line incorporates technology that Dr. Yarosh invented for drug applications, including the liposome delivery system that Dimericine uses.

"There are some who will say I've abandoned my principles in some way," says Dr. Yarosh. But "as a scientist, I know there are cosmetic products that work and many FDA-approved drugs that don't work."

'Incredible' Potential

For a sense of both the potential of cosmetic medicine and the patience required to coax a product from scientific breakthroughs, there may be no better illustration than wound care. This is one of the most promising areas of basic dermatology research. But many efforts at tissue engineering have stumbled, underscoring the complexities involved.

At the Wistar Institute in Philadelphia, researchers in the late 1990s were flabbergasted to discover that a particular mutation in laboratory mice led to scarless healing. The mice had been genetically altered to study lupus, an autoimmune disease. After holes were punched in the animals' ears for identification tags, the holes mysteriously disappeared. When researchers made new holes, they closed up again. A similar regenerative process occurred in the animals' heart tissue.

"It's like those science-fiction movies where someone is shot and the hole disappears," says Ellen Heber-Katz, a professor at the institute. She and her colleagues have been trying to identify the molecules responsible for this remarkable phenomenon. "We have lots of molecules that look interesting, but it takes time to test them," she says. But "if we could develop methods for getting rid of injured tissue and regrow tissue that is normal and new, it would be pretty incredible."

--Ms. Rundle is a news editor in The Wall Street Journal's Los Angeles bureau