Idebenone

Miami Beach -- Speaking on "The Biologic Basis of Cosmeceuticals" at the South Beach Symposium here, Patricia Farris, M.D., kept returning to one point: the importance of objective clinical studies to understand and support efficacy claims.

"Whether products are prescribed pharmaceutical agents or over-the-counter formulations, what our patients truthfully want to know is whether these products will make their skin look better. Of course, only objective clinical studies can answer that question," according to Dr. Farris, clinical assistant professor of dermatology at Tulane University School of Medicine in New Orleans.

More than semantics

It is Dr. Farris' contention that the widespread use of the word "cosmeceuticals" is more than an issue of semantics.

"As dermatologists, we need to use terms correctly," she tells Cosmetic Surgery Times. "Cosmeceuticals are over-the-counter skin care products that are a blend between cosmetics and pharmaceuticals. However, many refer to products like Renova (Ortho) and Avage (Allergan) as cosmeceuticals, but these are, in fact, pharmaceuticals whose efficacy is supported by FDA-required clinical studies.

"With so many options, it's up to dermatologists to discriminate the scientific information so we can best advise our patients about what works and what doesn't. Yet, too often we just don't know if products are effective, because they haven't been tested properly."

For example, she says, studies on the promising new antioxidant idebenone, the active ingredient in Allergan's Prevage, showed it to be superior to many other commonly used topical antioxidants.

"While this information is valuable, it's important to understand that these studies aren't looking at actives in formulation or actual products," Dr. Farris says. It's interesting to know which active offers the greatest antioxidant capacity, but since we can't test actual products in this way, the use of this data becomes more limited."

What causes aging?

"To understand the biological basis of products designed to improve the skin, you have to know something about what causes photoaging," Dr. Farris says.

Following ultraviolet light exposure, she explains, skin cells begin to accumulate reactive oxygen species. These reactive oxygen species not only damage cells and DNA in and of themselves, but they also trigger certain cellular and molecular events that also contribute to skin aging, most notably activation of the transcription factor AP-1. The up-regulation of AP-1 causes an increase in the production matrix metalloproteinases that break down collagen. It is this alteration in collagen homeostasis that contributes to skin aging.

Combatting aging effects

According to Dr. Farris, the first generation of so-called cosmeceuticals that came into the marketplace contained a variety of antioxidants.

"It makes sense based on what we know about photoaging that antioxidants should offer photoprotection," she observes. "But many antioxidants are difficult to stabilize in formulation. Also, many of these molecules are sensitive to light and oxidation, which is a big issue.

"It's also important to understand that just because an antioxidant offers photoprotection doesn't necessarily mean it repairs sun damage. In the case of retinol and vitamin C, we know that there are some reparative mechanisms that come into play. This is probably the reason that these two agents can improve the appearance of photodamaged skin. Both vitamin A and C stimulate collagen production. They have also been shown to lighten hyperpigmentation that further improves the appearance of sun-damaged skin. So with these two agents, we have both photo-protection and photo-repair, which is why they remain the gold standard for aging skin."

It is also perhaps the reason a second generation of cosmeceuticals focused on agents that turn on new collagen formation.

Activating fibroblasts

"These products work at a very different level--not by trying to attack free radicals and protect the skin from sun damage, but trying to repair by turning on the activity of the fibroblasts," Dr. Farris explains.

"We know that growth factors can activate fibroblasts, particularly transforming growth factor beta 1 (TGFbeta-1). So it's no surprise that growth factors have been touted in a number of cosmeceutical lines."

Dr. Farris says she would especially welcome larger objective clinical studies of the popular TNS Recovery Complex (SkinMedica), which she describes as "a kind of growth factor soup containing lots of different growth factors as well as antioxidants and soluble collagen proteins. "We don't exactly know what's working in this product, but there are preliminary clinical studies that suggest it improves the appearance of aging skin."

Another agent found to be effective at turning on fibroblasts, notes Dr. Farris, is pal-KTTKS, a pro-collagen fragment that has been shown in vitro to stimulate collagen production by cultured fibroblasts.

"There have been some industry-sponsored vehicle-controlled clinical studies that showed improvement in wrinkling; one actually compared pal-KTTKS to retinol. Both agents improved fine lines and wrinkles equally, but pal-LTTKS was less irritating."

She mentioned the recent proliferation of products that claim to have Botox-like effects on the skin. But she is skeptical.

"Most of the products contain the peptide argireline or acetyl hexapeptide-3. In vitro this compound appears to inhibit the secretion of neurotransmitters in a similar fashion to botulinum toxin."

However, she notes, "The agent would have to cross the epidermis, penetrate through the dermis and the fatty layer and penetrate all the way to the muscle to actually work."

Returning to her point, she stresses that there are no clinical studies confirming the effectiveness of this compound, and she considers the one, 10-patient open-label trial with 5 percent argerilene "limited."

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