INTRODUCTION

BRIEF ABSTRACT

By applying the properties of peptide signal sequences as genetic and metabolic feedback messengers, a novel peptide signal sequence complex was generated that significantly affects dermal metabolism and structure. Tests using this sequence have demonstrated a dose-dependent increase in fibroblast proliferation and an enhanced ability of the fibroblast to thrive in a stressful environment. Similar testing with murine hepatocytes revealed a significant increase in cellular respiration. The morphological changes associated with these metabolic responses include an increase in proline incorporation in the dermal matrix and an increase in the concentration of lysyl oxidase. These findings may contribute to accelerated regeneration of the dermal matrix, its enhanced durability, and an acceleration of the wound healing response.


ABSTRACT

The synthesis of a novel peptide, GC-100's signal sequence has been shown in early testing to significantly reverse some of the in vitro endpoints of cutaneous aging with positive clinical correlation. The signal sequence described has several independent mechanisms of action that include selective, dose-dependent fibroblast proliferation, an increase in the metabolic activity of the skin, and increase in collagen I and III syntheses as measured by a proline incorporation assay (with more than twice the end result when compared to retinoic acid 0025%), depression of tyrosinase activity, and a down-regulatory effect on proinflammatory prostaglandins in in vitro three-dimensional skin models. In vivo test results have demonstrated a significant acceleration of the wound healing response with associated anti-erythema properties. Pilot clinical studies have revealed an average 8% increase in epidermal thickness 6 weeks after application and a high level of patient satisfaction (p = 0.0225) regarding qualitative cosmetic changes in a population previously treated with retinoic acid or chemical peels.


SPECTRUM OF ACTIVITY FOR GC-100

GC-100 has been shown to selectively upregulate fibroblast proliferation and respiration while increasing fibroblast durability under unfavorable conditions. The structural consequences of these metabolic changes in the dermis include increased proline incorporation and accelerated collagen deposition. In addition, the observed elevation in lysyl oxidase concentrations may contribute to an accelerated maturation of the collagen matrix, as well as to an enhanced remodeling. phase during the wound healing process.

Clearly, the concept of signal sequence technology and its potential applications in genetics and medical therapeutics warrants further investigation. The experiments presented in this paper explored some of the metabolic and morphological consequences of applying a novel signal sequence complex, GC-100, to the skin. The findings presented raise a number of interesting questions and possibilities. In particular, what is the relationship, if any, between GC-100, the observed metabolic changes, and any genetic up - or down-regulation? Secondly, what is the relationship between proline deposition and changes in cellular metabolism? And thirdly, what is the potential of GC-100 to counter the effects of dermatohetiosis and intrinsic aging of the skin?

Since aging may be defined as the progressive, tirne-dependent deterioration of an organ system's structural or functional integrity, it is conceptually reasonable to conclude that GC-100’s ability to enhance the dermis' metabolism and structure contributes to a regeneration of the dermis and a reversal of some of the aging process. The basic science and clinical findings demonstrative of intrinsic aging and dermatohehosis are well established and have served as the basis for exploring treatment options that reduce or reverse signs of aging using different topical preparations. The majority of preparations include the familiar retinoic acid derivatives and alphahydroxy and beta-hydroxy acids. Based on our current understanding of GC-100, it should be positioned as a new class of active, with expected clinical efficacy beyond that of the retinoic acid derivatives.

It is hypothesized that the spectrum of activity for GC-100 is far broader than our current experimentation has revealed. The results obtained in the case study presented are promising and suggest that GC-100 may also exhibit an ability to counter the inflammatory response and minimize scarring potential. Further studies into wound heating are clearly warranted.


COMMENTS
According to the pilot study conducted at Ball Memorial Hospital, an affiliate of Indiana-
University School of Medicine, on women between the ages of 28 and so with moderate sun damage and age-induced brown spots and wrinkles. GC-100 increased skin thickness by an average of 8% and reduced irregular pigmentation by 54%. Skin was thickened due to increased production of Collagen I and Collagen III which are the key players in minimizing wrinkles.
Alongside this remarkable result, GC-100 treatments were non-irritating to the skin and clinically demonstrated their ability to reduce wrinkles, facial pigmentation spots, and other signs of aging and sun damage.