Efficacy of sunscreen with photolyase or regular sunscreen associated with topical antioxidants in treating advanced photodamage and cutaneous field cancerization: a randomized clinical trial.

BACKGROUND: Several treatments are available for skin with advanced photodamage, which is characterized by the presence of actinic keratoses (AK). OBJECTIVES: Evaluate the efficacy of using sunscreen with photolyase compared to regular sunscreen, as well as to compare the combination of a topical formulation of antioxidants versus placebo in the treatment of advanced photodamage. METHODS: This was a randomized, double-blind, factorial clinical trial. Participants with AKs on their forearms were randomized to apply regular sunscreen (SC) or sunscreen with photolyase (SC+P) on both forearms during the day. One of the forearms in each group was randomized again to receive topical antioxidants (AOx), and the other forearm received a placebo cream (both for night application). The four groups were SC/AOx, SC/placebo, SC+P/AOx, and SC+P/placebo. The duration of treatment was 8 weeks. Primary outcomes were total AK clearance, decrease in Forearm Photoaging Scale (FPS), and AK severity scores. Secondary outcomes were reduction in AK count, partial clearance rate, and safety. RESULTS: Forty participants (80 forearms) were included. All groups showed significant improvement in outcomes at week eight. There were no significant differences between SC and SC+P for either outcome. AOx led to a significant reduction in AK count (22%; p < 0.05). Partial clearance was obtained in 18 (47.4%) forearms treated with AOx and in 9 (23.7%) treated with placebo (p < 0.05). All groups reduced the FPS score, without significant differences among them. CONCLUSIONS: There is no difference in the treatment of advanced photodamage skin when comparing the use of sunscreen with photolyase and regular sunscreen, and topical antioxidants were more efficient in reducing AK count than placebo. STUDY LIMITATIONS: Short interval of follow-up and absence of re-evaluation in the absence of treatment were limitations of the present study.

What's New in Photoprotection: A Review of New Concepts and Controversies.

Cumulative ultraviolet exposure plays a critical role in photodamage. Recent advancements in photomedicine have resulted in a more thorough understanding of these mechanisms. Despite this, the adoption of routine sun protective practices is commonly not undertaken regularly by a large proportion of the public. Various obstacles exist that contribute to the public's nonadherence to these practices. Sunscreens, which are an integral component in all photoprotective regimens, have been questioned recently in terms of their safety. The aim of this article is to provide an overview of new concepts in photoprotection and also address current controversies pertaining to sunscreens.

The use of a sunscreen containing DNA-photolyase in the treatment of patients with field cancerization and multiple actinic keratoses: a case-series.

Cutaneous field cancerization (CFC) is associated witha high-risk of developing cutaneous squamous cellcarcinoma (cSCC). It manifests as actinic keratoses(AK) as one of the few macroscopic alterations in CFCpatients. A prospective, single-arm, case-series wasperformed to evaluate the utility of a novel sunscreencontaining DNA-photolyase for treatment of CFCin nine subjects (mean age 70.6 years, male: femaleratio 5:4). The cream was applied topically twicedaily on CFC/AK areas and patients were followedup for three months, with no other treatments. Theprimary outcome was the overall response rate (ORR),categorized as complete response (CR, completeresolution of AKs), partial response (PR, reduction inthe number of AKs), and no-response (NR, similar/increase in number of AKs). A 100% PR was observed.All subjects displayed at minimum, a 50% reductionin their lesion number and most patients experiencedalmost CR. Evaluation of AK numbers revealed anabsolute count reduction of 76.6% in the number oflesions, with the mean number of lesions reducedfrom 13.4 to 3.1 (p < 0.0001). No adverse events werereported. Patients with CFC may benefit from noveltopical applications containing DNA-photolyase,at minimum, as complementary therapy for themanagement of CFC disease. We propose a newconcept called "active photoprotection" because of itsdual mechanism involving therapy and protection.

Comparative Effects of Sunscreens Alone vs Sunscreens Plus DNA Repair Enzymes in Patients With Actinic Keratosis: Clinical and Molecular Findings from a 6-Month, Randomized, Clinical Study.

Recent experimental irradiation studies have shown that the addition of DNA repair enzymes (photolyase and endonuclease) to traditional sunscreens may reduce ultraviolet radiation (UVR)-induced molecular damage to the skin to a greater extent than sunscreens alone. In this 6-month, randomized, clinical study, we sought to compare the clinical and molecular effects of sunscreens plus DNA repair enzymes vs. those of traditional sunscreens alone in patients with actinic keratosis (AK). A total of 28 AK patients were randomized to topically apply sunscreens plus DNA repair enzymes (enzyme group; n = 14) or sunscreens alone (sunscreen group; n = 14) for 6 months. The main outcome measures included 1) hyperkeratosis, 2) field cancerization (as measured by fluorescence diagnostics using methylaminolaevulinate), and 3) levels of cyclobutane pyrimidine dimers (CPDs) in skin biopsies. Both regimens produced a significant reduction of hyperkeratosis at 6 months, with no difference between the two groups. Field cancerization was significantly reduced by both regimens, but the decrease observed in the enzyme group was significantly more pronounced than in the sunscreen group (P < 0.001). At 6 months, CPDs decreased by 61% in the enzyme group and by 35% in the sunscreen group compared with baseline values (P < 0.001). These findings indicate that, despite a similar effect on hyperkeratosis, the addition of DNA repair enzymes to sunscreens was more effective in reducing field cancerization and CPDs than sunscreens alone. Taken together, our findings indicate that sunscreens plus DNA repair enzymes may be superior to traditional sunscreens alone in reducing field cancerization and UVR-associated molecular signatures (CPDs) in AK patients, potentially preventing malignant transformation into invasive squamous cell carcinoma in a more efficient manner.

Efficacy of a photolyase-based device in the treatment of cancerization field in patients with actinic keratosis and non-melanoma skin cancer.

Eryfotona AK-NMSC (ISDIN Spain) is a film-forming medical device in cream or fluid formulation containing the DNA-repair enzyme photolyase and high-protection UV filters in liposomes (repairsomes) indicated in the treatment of cancerization field in patients with actinic keratosis (AK) or non-melanoma skin cancer (NMSC). Photolyase is an enzyme that recognizes and directly repairs UV-induced DNA damage. The most common UV-induced DNA damage is the formation of cyclobutane pyrimidine dimers (CPD). Clinical studies evaluating the histological and cellular effects of Eryfotona AK-NMSC have shown a potential benefit in the treatment of the cancerization field in AK patients. In particular the use of Eryfotona AK-NMSC improves the confocal microscopic appearance of skin at the cancerization field level. In addition, Eryfotona AK-NMSC improves the p53 gene expression at keratinocyte level. In this study we reported a series of 6 cases of patients with AK or NMSC lesions treated with Eryfotona AK-NMSC fluid, both as coadjuvant and as single treatment, applied twice daily in the affected area with photograph documentation. Clinical photographs of the skin lesions at baseline and after Eryfotona AK-NMSC treatment were taken in all cases using a high-definition digital camera. Six patients with multiple AK lesions of the scalp or face with or without NMSC were treated for a mean of 1-3 months with Eryfotona AK-NMSC fluid formulation. Image documentations before and after treatment of this clinical series show a great improvement in AK lesions count and of cancerization field. This clinical series supports the clinical efficacy of the use of photolyase and high-protection UV filters in the treatment of cancerization field and AK lesions in patients with actinic damage.

Novedades en fotoprotección / Update on Photoprotection

La fotoprotección es una estrategia preventiva y terapéutica fundamental frente al fotoenvejecimiento y el cáncer de piel. Este artículo recopila las novedades más relevantes en sustancias fotoprotectoras, tanto en fotoprotección tópica como sistémica. Comenzando por las nuevas aportaciones a los clásicos filtros químicos y físicos, pasando por la creciente incorporación de sustancias antioxidantes, las novedosas estrategias de reparación del daño solar en el ADN y el estado actual del uso de sustancias estimulantes de la melanogénesis. Por último, se revisa la protección frente a la radiación infrarroja (AU)

Photoprotection is the primary preventive and therapeutic strategy against photoaging and skin cancer. This review presents the most important new advances in both topical and systemic photoprotection. Starting with innovations in the traditional physical and chemical filtering agents, we go on to discuss the growing number of antioxidants, the novel strategies for repairing light-induced DNA damage, and current research on substances that stimulate melanogenesis. A final section deals with protection against infrared radiation (AU)

Repairing DNA damage in xeroderma pigmentosum: T4N5 lotion and gene therapy.

Patients with xeroderma pigmentosum (XP) have defective DNA repair and are at a high risk for cutaneous malignancies. Standard treatments for XP are limited in scope and effectiveness. Understanding the molecular etiology of XP has led to the development of novel therapeutic approaches, including enzyme and gene therapies. One new topical treatment utilizing bacteriophage T4 endonuclease 5 (T4N5) in a liposomal lotion is currently in clinical trials and has received a Fast Track designation from the FDA. Gene therapy for XP, while making leaps in preclinical studies, has been slower to develop due to tactical hurdles, but seems to have much potential for future treatment. If these treatments prove effective in lowering the risk of cancer in patients with XP, they may also be found useful in reducing skin cancers in other at-risk patient populations.

Effect of xenogenic repair enzymes on photoimmunology and photocarcinogenesis.

Exposure to ultraviolet B (UVB) radiation leads to an increased generation of UVB-induced skin damage in humans. The most important UVB-induced side effects are UVB-induced immunosuppression and photocarcinogenesis and there is a large body of evidence that cyclobutane pyrimidine dimers (CPD) induced by UVB radiation play a pivotal role in both processes. The topical application of DNA repair enzymes is a new innovative strategy to reduce the amount of CPDs in human skin. Two different methods have recently been established. The use of T4 endonuclease V was of clinical efficacy in protecting patients with a nucleotide excision repair defect from premalignant and malignant skin lesions. Application of photolyase, a xenogenic enzyme which has been found in different organisms is also capable of removing UVB-induced CPD from normal human skin cells in vivo and appears to be more effective than T4 endonuclease V in damage removal. Photolyase encapsulated in liposomes may have in the near future a broad use as an active ingredient in modern skin care products.

Enzyme plus light therapy to repair DNA damage in ultraviolet-B-irradiated human skin.

Ultraviolet-B (UVB) (290-320 nm) radiation-induced cyclobutane pyrimidine dimers within the DNA of epidermal cells are detrimental to human health by causing mutations and immunosuppressive effects that presumably contribute to photocarcinogenesis. Conventional photoprotection by sunscreens is exclusively prophylactic in nature and of no value once DNA damage has occurred. In this paper, we have therefore assessed whether it is possible to repair UVB radiation-induced DNA damage through topical application of the DNA-repair enzyme photolyase, derived from Anacystis nidulans, that specifically converts cyclobutane dimers into their original DNA structure after exposure to photoreactivating light. When a dose of UVB radiation sufficient to induce erythema was administered to the skin of healthy subjects, significant numbers of dimers were formed within epidermal cells. Topical application of photolyase-containing liposomes to UVB-irradiated skin and subsequent exposure to photoreactivating light decreased the number of UVB radiation-induced dimers by 40-45%. No reduction was observed if the liposomes were not filled with photolyase or if photoreactivating exposure preceded the application of filled liposomes. The UVB dose administered resulted in suppression of intercellular adhesion molecule-1 (ICAM-1), a molecule required for immunity and inflammatory events in the epidermis. In addition, in subjects hypersensitive to nickel sulfate, elicitation of the hypersensitivity reaction in irradiated skin areas was prevented. Photolyase-induced dimer repair completely prevented these UVB radiation-induced immunosuppressive effects as well as erythema and sunburn-cell formation. These studies demonstrate that topical application of photolyase is effective in dimer reversal and thereby leads to immunoprotection.