TY - JOUR
T1 - Topical niclosamide (ATx201) reduces Staphylococcus aureus colonization and increases Shannon diversity of the skin microbiome in atopic dermatitis patients in a randomized, double-blind, placebo-controlled Phase 2 trial
AU - Weiss, Anne
AU - Delavenne, Emilie
AU - Matias, Carina
AU - Lagler, Heimo
AU - Simon, Daniel
AU - Li, Ping
AU - Hansen, Jon U
AU - Dos Santos, Teresa Pires
AU - Jana, Bimal
AU - Priemel, Petra
AU - Bangert, Christine
AU - Bauer, Martin
AU - Eberl, Sabine
AU - Nussbaumer-Pröll, Alina
AU - Anne Österreicher, Zoe
AU - Matzneller, Peter
AU - Quint, Tamara
AU - Weber, Maria
AU - Nielsen, Hanne Mørck
AU - Rades, Thomas
AU - Johansen, Helle Krogh
AU - Westh, Henrik
AU - Kim, Wooseong
AU - Mylonakis, Eleftherios
AU - Friis, Christian
AU - Guardabassi, Luca
AU - Pace, John
AU - Lundberg, Carina Vingsbo
AU - M'Zali, Fatima
AU - Butty, Pascal
AU - Sørensen, Nikolaj
AU - Nielsen, Henrik Bjørn
AU - Toft-Kehler, Rasmus
AU - Guttman-Yassky, Emma
AU - Stingl, Georg
AU - Zeitlinger, Markus
AU - Sommer, Morten
N1 - © 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
PY - 2022
Y1 - 2022
N2 - BACKGROUND: In patients with atopic dermatitis (AD), Staphylococcus aureus frequently colonizes lesions and is hypothesized to be linked to disease severity and progression. Treatments that reduce S. aureus colonization without significantly affecting the skin commensal microbiota are needed.METHODS AND FINDINGS: In this study, we tested ATx201 (niclosamide), a small molecule, on its efficacy to reduce S. aureus and propensity to evolve resistance in vitro. Various cutaneous formulations were then tested in a superficial skin infection model. Finally, a Phase 2 randomized, double-blind and placebo-controlled trial was performed to investigate the impact of ATx201 OINTMENT 2% on S. aureus colonization and skin microbiome composition in patients with mild-to-severe AD (EudraCT:2016-003501-33). ATx201 has a narrow minimal inhibitory concentration distribution (.125-.5 μg/ml) consistent with its mode of action - targeting the proton motive force effectively stopping cell growth. In murine models, ATx201 can effectively treat superficial skin infections of methicillin-resistant S. aureus. In a Phase 2 trial in patients with mild-to-severe AD (N = 36), twice-daily treatment with ATx201 OINTMENT 2% effectively reduces S. aureus colonization in quantitative colony forming unit (CFU) analysis (primary endpoint: 94.4% active vs. 38.9% vehicle success rate, p = .0016) and increases the Shannon diversity of the skin microbiome at day 7 significantly compared to vehicle.CONCLUSION: These results suggest that ATx201 could become a new treatment modality as a decolonizing agent.
AB - BACKGROUND: In patients with atopic dermatitis (AD), Staphylococcus aureus frequently colonizes lesions and is hypothesized to be linked to disease severity and progression. Treatments that reduce S. aureus colonization without significantly affecting the skin commensal microbiota are needed.METHODS AND FINDINGS: In this study, we tested ATx201 (niclosamide), a small molecule, on its efficacy to reduce S. aureus and propensity to evolve resistance in vitro. Various cutaneous formulations were then tested in a superficial skin infection model. Finally, a Phase 2 randomized, double-blind and placebo-controlled trial was performed to investigate the impact of ATx201 OINTMENT 2% on S. aureus colonization and skin microbiome composition in patients with mild-to-severe AD (EudraCT:2016-003501-33). ATx201 has a narrow minimal inhibitory concentration distribution (.125-.5 μg/ml) consistent with its mode of action - targeting the proton motive force effectively stopping cell growth. In murine models, ATx201 can effectively treat superficial skin infections of methicillin-resistant S. aureus. In a Phase 2 trial in patients with mild-to-severe AD (N = 36), twice-daily treatment with ATx201 OINTMENT 2% effectively reduces S. aureus colonization in quantitative colony forming unit (CFU) analysis (primary endpoint: 94.4% active vs. 38.9% vehicle success rate, p = .0016) and increases the Shannon diversity of the skin microbiome at day 7 significantly compared to vehicle.CONCLUSION: These results suggest that ATx201 could become a new treatment modality as a decolonizing agent.
KW - Animals
KW - Anti-Bacterial Agents/pharmacology
KW - Dermatitis, Atopic/drug therapy
KW - Humans
KW - Methicillin-Resistant Staphylococcus aureus
KW - Mice
KW - Microbiota
KW - Niclosamide/pharmacology
KW - Ointments/pharmacology
KW - Staphylococcal Infections/drug therapy
KW - Staphylococcus aureus
U2 - 10.1002/ctm2.790
DO - 10.1002/ctm2.790
M3 - Journal article
C2 - 35522900
VL - 12
JO - Clinical and Translational Medicine
JF - Clinical and Translational Medicine
SN - 2001-1326
IS - 5
M1 - e790
ER -