Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Bacterial biofilm formation inside colonic crypts may accelerate colorectal carcinogenesis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Anne Weiss
  • Emilie Delavenne
  • Carina Matias
  • Heimo Lagler
  • Daniel Simon
  • Ping Li
  • Jon U Hansen
  • Teresa Pires Dos Santos
  • Bimal Jana
  • Petra Priemel
  • Christine Bangert
  • Martin Bauer
  • Sabine Eberl
  • Alina Nussbaumer-Pröll
  • Zoe Anne Österreicher
  • Peter Matzneller
  • Tamara Quint
  • Maria Weber
  • Hanne Mørck Nielsen
  • Thomas Rades
  • Helle Krogh Johansen
  • Henrik Westh
  • Wooseong Kim
  • Eleftherios Mylonakis
  • Christian Friis
  • Luca Guardabassi
  • John Pace
  • Carina Vingsbo Lundberg
  • Fatima M'Zali
  • Pascal Butty
  • Nikolaj Sørensen
  • Henrik Bjørn Nielsen
  • Rasmus Toft-Kehler
  • Emma Guttman-Yassky
  • Georg Stingl
  • Markus Zeitlinger
  • Morten Sommer
Vis graf over relationer

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.

OriginalsprogEngelsk
Artikelnummere790
TidsskriftClinical and Translational Medicine
Vol/bind12
Udgave nummer5
Sider (fra-til)1-21
Antal sider21
ISSN2001-1326
DOI
StatusUdgivet - maj 2022

Bibliografisk note

© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.

ID: 77846860