Efficacy

The peptide pal-KTTKS has been shown to be quite potent clinically, providing effects from very low topical doses. This low dose for clinical activity is consistent with the very low concentration (as low as ppb) required to obtain effects in vitro as noted above. In small-base human clinical testing (54), topical pal-KTTKS at 3 ppm was described as providing improvement in appearance of wrinkled skin. To confirm this observation, a larger base size 12-week, double-blind, placebo-controlled, split-face, left-right randomized study (n = 94) was conducted (43), again testing the effect of topical 3 ppm pal-KTTKS. This topical peptide is extremely well tolerated by test subjects, i. e., it does not induce skin irritation responses (no redness, dryness, burn, sting, or itch responses). Based on quantitative computer image analysis, it reduced fine lines/wrinkles versus the placebo control (Fig. 11). While the effect was small, it was significant at weeks 8 and 12. Expert graders evaluating blind-coded images also identified an improvement in fine lines/ wrinkles, with directional and significant effects noted at weeks 8 and 12, respectively (Fig. 12). Consistent with the good skin tolerance of the peptide, there was no impact on skin barrier function, as assessed by TEWL (Table 1), indicating lack of irritation.

In contrast to the potency of pal-KTTKS, the reported effects of other peptides require much higher doses, such as 2% for Cu-GHK and as high as 10% for Ac-EEMQRR. There is also limited published information available on the clinical effects of these peptides. One study (55) describes increases in skin thickness, hydration, and smoothness from topical use of a commercial product containing Cu-GHK (peptide dose not indicated) in an open-label study involving 40 subjects. A series of clinical studies of eight to 12 weeks, duration (up to n = 71) describing skin improvements such as reduced

□ control □ 3 ppm pal-KTTKS

Figure 11 Topical pal-KTTKS improves the appearance of facial skin wrinkles (quantitative computer image analysis). Smaller numbers indicate fewer fine lines/wrinkles.

wrinkling, apparently using topical 2% Cu-GHK, have been presented as meeting posters (56-59). For Ac-EEMQRR, a conference platform presentation (53) describes 30% reduction in wrinkle depth with 10% of this peptide used topically in a 30-day study.