Wrinkle Drug's Action Is Found
By RHONDA L. RUNDLE
A popular injectable antiwrinkle treatment, Restylane, appears to stimulate skin cells to make natural collagen, a basic skin protein, according to a study whose findings suggest Restylane's effects may last longer than expected.
Restylane, sold in the U.S. by Medicis Pharmaceutical Corp., has been thought to smooth wrinkles by physically filling space created through collagen loss and other aging processes. The study by University of Michigan Medical School researchers, in this month's Archives of Dermatology, suggests the product's temporary benefits are also caused by a biological response, which explains why injections seem to have longer-lasting results after repeated treatments.
"The article is an important one because it begins to build a scientific basis for a cosmetic procedure that has historically just been based on the end result," said David J. Leffell, professor of dermatology and surgery at Yale University School of Medicine.
"I wish we could require more of this kind of data prior to product approval," said Amy Newburger, a Scarsdale, N.Y. dermatologist and consultant to the Food and Drug Administration.
The study focuses on skin cells known as fibroblasts. "In the last few years, we've learned that a basic problem in aging skin caused by ultraviolet light is that the fibroblasts that make collagen down deep in the skin have collapsed and flattened on each other," said John J. Voorhees, chairman of the university's dermatology department, which has been studying the causes of aging skin for over 20 years.
In a young person, the fibroblasts that make collagen are normally "stretched," Dr. Voorhees said. The study using Restylane was designed to see if the fibroblasts could be "restretched" and "that is exactly what happened," he said, noting that "the stretching caused the cells to make collagen like they did when they were young."
The initial antiwrinkle benefit of Restylane is caused by its "physical presence," but after three or four weeks, new collagen formation begins, the study showed. Dr. Voorhees said it isn't clear how long the new growth continues because the study was for only 13 weeks. The Restylane injections also inhibited the breakdown of collagen by an enzyme that acts on aging skin.
The study explains why Restylane seems to last longer after the first few injections, typically six to 12 months apart, dermatologists said. "To me, this is a validation of what we've seen clinically," said William P. Coleman III, clinical professor of dermatology at Tulane University Health Sciences Center. The cumulative effects of collagen growth "would theoretically apply to all hyaluronic acid fillers," he added. Juvéderm, introduced by Allergan Inc. in January, is a hyaluronic acid that competes against Restylane.
But Dr. Voorhees cautioned against generalizing the findings to other substances because of their technical differences. That is also the view of June Robinson, editor of the Archives of Dermatology, published by the American Medical Association. "This is heavy science and only one brand was used," she said.
Dr. Robinson said the study "is the definitive paper that tells us how this product works." It was based on injections in 11 volunteers, aged 64 to 84, and subsequent analyses of their skin biopsies. The small number of subjects is "perfectly valid," she said, because this was a "mechanism study," not a clinical study.
Dr. Robinson said she took elaborate steps to assure that the research wasn't tainted by commercial ties between Medicis, of Scottsdale, Ariz., and the researchers. "The manufacturer of the product had nothing to do with the study except to donate material for it," she said. Dr. Voorhees said Restylane was chosen because when the research began, "it was the only hyaluronic acid out there."