Topical S. aureus – Targeting Endolysin Significantly Improves Symptoms and QoL in Individuals With Atopic Dermatitis

December 2021 | Volume 20 | Issue 12 | Original Article | 1323 | Copyright © December 2021

Published online November 29, 2021

Magali Moreau PhD,a Sophie Seité PhD,b Luc Aguilar PhD,c Olivier Da Cruz MSc,d Julia Puech PharmD,d Johan Frieling MD PhD,e Ann’Laure Demessant PharmDb

aL’Oréal Recherche & Innovation, Clark, NJ
bLa Roche Posay Dermatological Laboratories, Levallois Perret, France
cL'Oreal R&I, Aulnay-Sous-Bois, France
dL’Oréal R&I, Chevilly Larue, France
eMicreos Human Health, Bilthoven,The Netherlands

Atopic dermatitis (AD) is a chronic skin condition affecting an increasing number of children and adults whose quality of life is impacted by chronic itch and pain. It is characterized by an altered epidermal barrier, skin inflammation, and skin microbiome dysbiosis particularly over-colonization of Staphylococcus aureus. The efficacy and tolerance of a cream containing a S. aureus-targeting technology (endolysin) was assessed in an open-label, two-week study in children and adults with mild-to-moderate atopic dermatitis. A total of 43 patients ranging from 7 months to 57 years old were included and all patients finished the study without any tolerance problem. Disease severity, measured with SCORAD, quickly reduced by 43% in 7 days and by 68 % in 14 days. The benefit was perceived by the whole panel with a marked improvement in overall QoL. This study shows the efficacy of a highly specific S. aureus-targeted technology in alleviating symptoms and improving QoL in children and adults with atopic dermatitis. It could also be beneficial in reducing and preventing flares in subjects with S. aureus load due to its good tolerance and specific action.

J Drugs Dermatol. 2021;20(12):1323-1328. doi:10.36849/JDD.6363


Atopic dermatitis (AD) affects 20% of infants and adolescents and up to 3% of adults worldwide1,2 and its incidence is increasing globally.3 AD causes erythema, constant intense itching,4 and psychological distress5 which negatively impacts quality of life (QoL) more than other chronic conditions such as heart disease or diabetes.6 In children, it has the second highest impact on QoL.7

AD is a chronic inflammatory skin condition associated with epidermal barrier dysfunction, abnormal immune response, and skin microbiome imbalance.8 These three factors are interdependent thus enabling AD symptoms to be managed from multiple angles. Skin microbiome dysbiosis is often characterized by low skin microbial diversity compared to healthy skin and an over-colonization of S. aureus.9 S. aureus levels are associated with AD disease severity, flare frequency and symptoms that directly impact QoL.10-12 Its toxins stimulate proinflammatory cytokine and chemokine production causing itching, burning sensations, and pain,13,14 and create a vicious itch-scratch cycle.15-17

During AD flares, treatment aims to reduce inflammation and itching, rebuild the epidermal barrier, and prevent secondary infections.18 Appropriate moisturizers and cleansers are cornerstones of AD management to address skin barrier dysfunction.19 Topical corticosteroids (TCS) are first-line treatment for flares since they effectively reduce inflammation.20 However, their use is limited to avoid developing skin atrophy in sensitive skin areas.21 Furthermore, patients express concerns (corticophobia) which can impactTCS use, adherence to treatment and overall effectiveness.22 Secondary infection, particularly by S. aureus, can be treated with broad spectrum or anti-staphylococcal antibiotics20 but these can damage the beneficial skin microbiota and potentially lead to antibiotic resistance.23 Considering the mounting evidence pointing towards the major negative role of S. aureus in AD and the beneficial role of the skin microbiome for skin homeostasis, a treatment exclusively targeting S. aureus offers many advantages.24

Many microbial ecosystems, including the skin microbiome, harbor viruses called bacteriophages that only infect bacteria.25 Bacteriophages are specific for their target bacteria, and at the end of their lytic cycle induce the production of enzymes, called endolysins, which degrade the peptidoglycan of the bacterial cell wall from within, causing cell lysis and progeny virion release. Since Gram-positive bacteria, such as S. aureus,