STUDIES DEMONSTRATE VALUE OF PROCOLLAGEN FRAGMENT PAL-KTTKS
Pal-KTTKS improves wrinkle appearance without causing irritation; shows positive changes in elastin

By Cheryl Guttman, Staff Correspondent Dermatology Times
Vol. 23, No. 9 September 2002

Paris- Results from a series of studies presented at the World Congress of Dermatology support the conclusion that palmitoyl-pentapeptide 3 (Pal-KTTKS) is a very safe and effective agent for improving the appearance of photoaged facial skin.

Pal-KTTS (Matrixyl) is modified chain off aminoacids developed as a cosmetic active ingredient and patented, manufactured, and sold for commercial use by the French company Sederma SA. Results of a Sederma-sponsored study demonstrated topical application of a product containing 3 ppm Pal-KTTKS improved wrinkle appearance more quickly than retinals and without causing irritation. The clinical benefits of Pal-KTTKS were confirmed in a separate study that also included histological assessments showing positive changes in elastin and collagen IV.

The efficacy and safety of the modified pentapeptide were also demonstrated in a randomized, double-blind, split-faced clinical study undertaken by Proctor & Gamble, in which objective and subjective outcome assessments performed after 12 weeks of treatment showed significant benefits of the active formulation for reducing the appearance of fine lines and wrinkles, age spots, and skin firmness. Those improvements occurred with excellent tolerability and without compromising barrier function.

Pal-KTTKS has undergone extensive in vitro and in vivo testing, including a wide range of toxicological investigations and with data being reported on more than 200 panelists participating in five independent clinical trials. "Based on the evidence accumulated through that research program, I think it is fair to state that this active peptide is a viable alternative to retinoids, in particular retinal, for wrinkle repair. To our knowledge, its high potency, ease of formulation, and the total absence of irritation potential set it apart from any other wrinkle treatment active presently proposed for cosmetic applications," said Karl Lintner, Ph.D., managing and technical director, Sederma SA, Paris.

"Pal-KTTKS appears to be very intriguing technology. We are keeping it in our arsenal of active ingredients to consider for future products, and currently we are continuing our formulation work to develop and aesthetically pleasing product for future testing", said Donald L. Bissett, Ph.D., a research fellin in the Skin Care Group, The Proctor & Gamble Co., Cincinnati, Ohio.

The Sederma-sponsored histological study was undertaken with the collaboration of Jean Revuz, M.D., professor of dermatology, Hospital Mondor, France, and president, 20th World Congress of Dermatology. It was a four-month, double-blind study in which 49 women applied Pal-KTTLS (n=22) or vehicle (n=27) twice daily to the face and decollet. Profilometry and 3d digital image analysis showed sites treated with Pal-KTTKS exhibited exhibited significant improvements in skin roughness (-13 percent), wrinkle volume (-36 percent) and wrinkle depth (-27 percent), while there were no changes in any of those endpoints with the vehicle.

Skin biopsies were taken from six women after two and four months, and the results were consistent with the clinical benefits observed. Ths histological assessments showed Pal-KETTS application was associated with theincreases in elastin fiber density and thickness and improved regularity of collagen IV at the dermal-epidermal junction, Dr. Lintner reported.

"Both of these proteins are critical supporting elements in smoothm, supple skin," he said.

The active controlled study compared the effects of cosmetic creams containing Pal-KTTKS 3 ppm or retinal 700 ppm on photoaged skin in 16 subjects. It used split-face, double-blind design and included profilomentry, echoghraphy, and clinical assessments after two and four months of treatment.

A benefit of Pal-KTTKS over retinal for reducing wrinkles was noted after two months and that occurred in the absence of irritation reactions. At study conclusion, further improvement in wrinkles and over-all roughness was noted in Pal-KTTKS-treated skin along with a average 9 percent increase in skin thickness in Pal-KTTKS-treated skin. At the same time, similar changes were noted with retinal treatment.

"DNA array studies show that both Pal-KTTKS and retinal activate genes associated with wound healing mechanisms, but that Pal-KTTKS does not elicit the pro-inflammatory actions associated with retinal," Dr. Lintner said.

"The mechanism studies indicate that KTTPS, like retinoids, improves the appearance of photodamaged skin by stimulating collagen production, however, it seems to do so without causing the irritation thatis associated withretinoids. That can be an important benefit in clinical use because a lot of consumers avoid or discontyinue topical retinoids because of the side effects," Dr. Bissett said.

Study Parameters

The Proctor & Gamble study he conducted enrolled 92 women aged 35 to 55 years of age with moderate to severe photo-damage and Fitzpatrick skin types I to III. After a two-week preconditioning period, women began applying Pal-KTTKS in a moisturizing base to one side of the face twice daily and the vehicle contralaterally. No other skin care products except for a supplied facial cleanser and broad spectrum UV sunscreen were allowed.

Changes in fine lines and wrinkles were assessed by comparisons of high-resolution digital images taken at baseoine and every four weeks during treatment. Efficacy was assessed both by digital image analysis and trained graders, and the study participants were asked to rate effects on their skin appearance.

Treatment benefits for improving fine lines and wrinkles were noted as early as four weeks after starting Pal-KTTKS application. At 12 weeks, wrinkle length was reduced from 170-4 mm at baseline to 147.7 mm and the participants subjective ratings indicated significant benefits for improving age spots, dark circles, and skin firmness.

"The study methods also included measurement of transepidermal water loss at baseline and every four weeks, and those results revealed no negative effects of Pal-KTTKS on the skin barrier, and overall the treatment was very well tolerated," Dr. Bissett reported.

KTTKS, a fragment of alpha-pro-collaagen I, was originally synthesized and investigated at the University of Tennessee based on knowledge that collagen fragments might act through a feedback mechanism to regulate collagen synthesis. Initial studies performed by those investigators in fibroblast cultures showed the pentapeptide increased production of the extracellular matrix proteins collagen I, collagen III and fibronectin. That activity prompted interest in the potential value of KTTKS as an ingredient in anti-aging skin products.

However, as percutaneous penetration of the water-soluble, charged peptide is poor, scientists at Sederma conjugated KTTKS with palmitoyl, a 16-carbon fatty acid moiety. They confirmed the modified compound diffuses through the stratum corneum and into the skin and showed in vitro and ex vivo that it increases collagen I and glycosaminoglycan synthesis.

DT

"To our knowledge, its(Pal-KTTKS) high potency, easy of formulation, and total absence of irritation potential set it apart from any other wrinkle treatment active presently proposed for cosmetic applications".

Karl Lintner, Ph.D

Late-Breaking News!