Heparan sulfate

The discussion this month focuses on an exciting new ingredient that is showing great promise as a topical antiaging agent. For years we have known that aging skin needs more collagen, elastin, and hyaluronic acid. It is time to add a new player to the antiaging team – heparan sulfate (HS). New studies have shown that lower levels of HS are associated with aged skin. This is what you need to know.

Significance of HS

Endogenous HS, an essential glycosaminoglycan (GAG), contributes to skin development and homeostasis, and thus actively promotes skin health.¹ GAGs such as HS and hyaluronic acid are well known as endogenous superhydrators that bind and retain water, thus contributing to skin hydration as well as preserving the structural integrity of collagen and elastin fibers. Specifically, HS and its protein-bound forms (HS proteoglycans such as syndecan, glypican, and perlecan) – the most common constituents on the cell surface and in the extracellular matrix (ECM) – play an important role in cutaneous cell proliferation, migration, communication, and activation as well as collagen fiber development, basement membrane regeneration, granulation tissue formation, and cell adhesion related to wound healing.¹ This results from their capacity to bind, store, present, degrade, and amplify growth factors and cytokines.

Accordingly, mature skin would be potently activated by its endogenous growth factors (at lower concentration) as cell signal is amplified (lower threshold of activation) by HS analogs. When used topically, HS analogs appear to promote the formation of healthy and functional ECM, resulting in firmer, more elastic, and stronger skin. Augmenting the amount of HS in the skin may yield a rejuvenating effect by expanding the skin’s ability to hold water and restore cutaneous homeostasis. Studies with an HS analog have demonstrated that the formulation penetrates into skin, enhancing hydration, reducing transepidermal water loss, and improving the appearance of wrinkles and skin tone.¹ The use of HS analogs or mimics, known as matrix therapy, has been shown to be effective clinically in cutaneous and corneal healing formulations, exhibiting proof of concept in humans, according to Barritault et al.³

Matrix therapy also has been employed successfully in plastic and aesthetic procedures. Zakine et al. assessed the impact of using ReGeneraTing Agents (RGTA) – biodegradable polymers designed to mimic HS in the ECM of damaged tissue – in 17 patients with breast hypertrophy who underwent mammoplasty. Patients received topical treatment on one breast 1, 4, 8, and 11 days after surgery. The investigators also evaluated a different group of 50 patients after centrofacial lifting. These patients received RGTA drops bilaterally in the treatment area after surgery. Inflammation, hypertrophic scars, and pruritus were noted less frequently for the breasts treated with RGTA. Similarly, in patients receiving a centrofacial lift, scar inflammation, edema, and bruising were significantly less frequent in the treated group (10%), compared with the untreated group (90%).⁴

In 2015, Gallo et al. reported that 15 patients using a new HS analog formulation in an 8-week study displayed improvement in various skin metrics, including hydration, firmness, elasticity, barrier function, and the appearance of fine lines and wrinkles. The investigators concluded that photodamaged skin may benefit from the use of novel topically applied products containing low-molecular-weight HS.¹

The synthetic heparan sulfate Cacipliq20 was reported in 2015 to have been used successfully to treat a chronic lower-extremity ulcer in a 22-year-old male patient with Stewart-Bluefarb syndrome,⁵ and in 2016 to treat a refractory sickle cell ulcer, with the encouraging outcome demonstrated by complete wound coverage and significant improvement in pain score.⁶ In 2012, Polieri et al. showed that HS 1% cream was comparable or more effective than glycosaminoglycan-polysulphate gel in alleviating the signs and symptoms of hematomas or subcutaneous hematic extravasations in a study with 96 white men and women.⁷

Conclusion

Heparan sulfate does appear to be a novel viable antiaging option. Endogenous heparan sulfate is involved in skin defense against pathogens, dehydrated/dried skin, redness, and wound healing. Theoretically, then, HS analogs should be able to modulate these processes. More research is necessary to determine if this is the case, however. In the meantime, HS analogs are extremely well tolerated by all patients and especially those with sensitive skin, which is often the case with aging skin. Further, HS analogs promote skin hydration, providing resistance to compressive forces as well as keeping skin looking healthy. Anecdotally, I can report that I have been using the Senté Dermal Repair Cream in my rosacea patients without any problems. I think HS analogs represent a good option for patients who cannot tolerate retinoids.