Rejuvenating Hydrator: Restoring Epidermal Hyaluronic Acid Homeostasis With Instant Benefits

January 2016 | Volume 15 | Issue 1 | Supplement Individual Articles | 24 | Copyright © January 2016


Vic A. Narurkar MD,a Sabrina G. Fabi MD FAAD FAACS,b Vivian W. Bucay MD FAAD,c Ruth Tedaldi MD,d Jeanine B. Downie MD,e Joshua A. Zeichner MD,f Kimberly Butterwick MD,g Amy Taub MD,h Kuniko Kadoya PhD,i Elizabeth T. Makino BS MBA CCRA,i Rahul C. Mehta PhD,i and Virginia L. Vega PhDi

aBay Area Laser Institute, San Francisco, CA
bDepartment of Dermatology, University of California San Diego, CA
cBucay Center for Dermatology and Aesthetics, San Antonio, TX
dDermatology Partners, Inc, Wellesley, MA
eImage Dermatology, Montclair, NJ
fDepartment of Dermatology, Mount Sinai Hospital, New York, NJ
gCosmetic Laser Dermatology, La Jolla, CA
hAdvanced Dermatology, Lincolshire, IL
iResearch & Development, SkinMedica Inc., an Allergan Company, Irvine, CA

for HA-binding protein (Figure 4B) upon treatment with HA5. Taken together, these data strongly suggest a boost in endogenous epidermal HA synthesis and deposition in response to HA5 treatment.

Clinical Testing

Instant and long-term effects after HA5 treatment were assessed by an open-label, single-center clinical study.
Instant effects were evaluated at baseline visit after applying a thin layer of the HA5 (nickel-sized amount) onto the entire face. We observed statistically significant improvements in mean scores for fine (periocular and forehead) lines/wrinkles and tactile roughness (Figure 5) within 15 minutes of application of HA5 (all P≤.03). In addition, HA5 also increased intrinsic skin moisture content as measured by corneometer instrumentation (Figure 5). Figure 6 shows representative standardized digital photographs, with the visualization of the instant smoothing effects within 15 min of HA5 application.
Long-term effects were assessed at weeks 1, 4, and 8 after treatment with HA5 (twice daily). We observed a significant improvement in mean scores for fine (periocular and forehead) lines/wrinkles and tactile roughness (all P≤.04) at all follow-up visits (Figure 7). Thus, treated skin showed a continuous increase in skin moisture content (hydration) at weeks 1, 4, and 8 compared with untreated (baseline) skin (Figure 8). Figure 8 shows representative standardized digital photographs of 2 subjects at weeks 4 and 8, respectively. Use of HA5 produced high ratings in self-perceived efficacy from the subject questionnaires at all visits (long-term effects) as well as immediately after application (instant effects). For example, 96% of subjects noticed an improvement in the smoothness and softness of their skin after 1 week of use. Eighty-eight percent agreed that the HA5 increased skin radiance and softened the look of lines and wrinkles at week 4, and by week 8, 87% of subjects agreed that their skin felt rejuvenated.
Overall, the HA5 formulation was well-tolerated with mean tolerability scores remaining similar to baseline (untreated) scores. Three subjects withdrew from the study due to acne breakout (n=1) and under eye dryness (n=2).Thus, these data suggest that the temporary nature of the increased hydration is biologically significant and, if used regularly, HA5 triggers a significant increase in endogenous HA because of enhanced biosynthesis as well as decreased degradation. On the other hand, the potential role in decreasing the inflammatory cascade has far-reaching implications for many conditions that individuals battle on a daily basis.

CONCLUSION

For decades HA has been considered a filler for empty spaces in the skin, though recent data have proven that HA is a specially active molecule in the skin and controls cell proliferation, differentiation, acute and chronic inflammation, and allergic reactions, in addition to trapping water and maintaining skin hydration. Thus, we developed the concept of BIOHYDRATION in which the benefits associated with the restoration of epidermal HA levels are not limited to increase water-binding capacity but also include promoting or restoring epidermal homeostasis as well as controlling inflammation. HA5 application results in instant improvements in skin quality parameters and, within time, retrains the skin to enhance endogenous epidermal HA production.

DISCLOSURES

Virginia L. Vega, Rahul C. Mehta, Elizabeth T. Makino, and Kuniko Kadoya are employees of SkinMedica, an Allergan Company. The other authors have no relevant conflicts of interest to disclose.

ACKNOWLEDGMENTS

We would like to thank Robin Gunawan for providing us with unpublished data and Tina Fleck for her key contributions to the development of this product.

REFERENCES

  1. Meyer K, Palmer JW. The polysaccharide of the vitreous humor. J Biol Chem. 1934;107:629-634.
  2. Meyer K. The action of hyaluronidases on hyaluronic acid. Ann NY Acad Sci. 1950;52(7):1021-1023.
  3. Shigeishi H, Higashikawa K, Takechi M. Role of receptor for hyaluronan-mediated motility (RHAMM) in human head and neck cancers. J Cancer Res Clin Oncol. 2014;140(10):1629-1640.
  4. Tammi MI, Day AJ, Turley EA. Hyaluronan and homeostasis: a balancing act. J Biol Chem. 2002;277(7):4581-4584.
  5. Heldin P, Basu K, Olofsson B, Porsch H, Kozlova I, Kahata K. Deregulation of hyaluronan synthesis, degradation and binding promotes breast cancer. J Biochem. 2013;154(5):395-408.
  6. Vigetti D, Karousou E, Viola M, Deleonibus S, De Luca G, Passi A. Hyaluronan: biosynthesis and signaling. Biochim Biophys Acta. 2014;1840(8):2452-2459.
  7. Cowman MK, Matsuoka S. Experimental approaches to hyaluronan structure. Carbohydr Res. 2005;340(5):791-809.
  8. Fraser JR, Laurent TC, Laurent UB. Hyaluronan: its nature, distribution, functions and turnover. J Intern Med. 1997;242(1):27-33.
  9. Tammi R, Säämänen AM, Maibach HI, Tammi M. Degradation of newly synthesized high molecular mass hyaluronan in the epidermal and dermal compartments of human skin in organ culture. J Invest Dermatol. 1991;97:126-130.
  10. Anderegg U, Simon JC, Averbeck M. More than just a filler – the role of hyaluronan for skin homeostasis. Exp Dermatol. 2014;23(5):295-303.
  11. Weigel PH, DeAngelis PL. Hyaluronan synthases: a decade-plus of novel glycosyltransferases. J Biol Chem. 2007;282(51):36777-36781.
  12. Karousou E, Kamiryo M, Skandalis SS, et al. The activity of hyaluronan synthase 2 is regulated by dimerization and ubiquitination. J Biol Chem. 2010;285(31):23647-23654.
  13. Itano N, Sawai T, Yoshida M, et al. Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties. J Biol Chem. 1999;274(35):25085-25092.
  14. Vigetti D, Genasetti A, Karousou E, et al. Modulation of hyaluronan synthase activity in cellular membrane fractions. J Biol Chem. 2009;284(44):30684-30694.
  15. Rilla K, Oikari S, Jokela TA, et al. Hyaluronan synthase 1 (HAS1) requires higher cellular UDP-GlcNAc concentration than HAS2 and HAS3. J Biol Chem. 2013;288(8):5973-5983.
  16. Siiskonen H, Kärnä R, Hyttinen JM, Tammi RH, Tammi MI, Rilla K. Hyaluronan synthase 1 (HAS1) produces a cytokine-and glucose-inducible, CD44-dependent cell surface coat. Exp Cell Res. 2014;320(1):153-163.
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