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Topical application of an irreversible small molecule inhibitor of lysyl oxidases ameliorates skin scarring and fibrosis

Author

Listed:
  • Nutan Chaudhari

    (The University of Western Australia
    The University of Western Australia)

  • Alison D. Findlay

    (Pharmaxis Ltd)

  • Andrew W. Stevenson

    (The University of Western Australia)

  • Tristan D. Clemons

    (The University of Western Australia
    University of Southern Mississippi)

  • Yimin Yao

    (Pharmaxis Ltd)

  • Amar Joshi

    (Pharmaxis Ltd)

  • Sepidar Sayyar

    (University of Wollongong
    University of Wollongong)

  • Gordon Wallace

    (University of Wollongong
    University of Wollongong)

  • Suzanne Rea

    (Burns Service of Western Australia, WA, Department of Health)

  • Priyanka Toshniwal

    (The University of Western Australia)

  • Zhenjun Deng

    (The University of Western Australia)

  • Philip E. Melton

    (University of Tasmania
    Curtin University
    University of Western Australia)

  • Nicole Hortin

    (The University of Western Australia)

  • K. Swaminathan Iyer

    (The University of Western Australia)

  • Wolfgang Jarolimek

    (Pharmaxis Ltd)

  • Fiona M. Wood

    (The University of Western Australia
    Burns Service of Western Australia, WA, Department of Health)

  • Mark W. Fear

    (The University of Western Australia)

Abstract

Scarring is a lifelong consequence of skin injury, with scar stiffness and poor appearance presenting physical and psychological barriers to a return to normal life. Lysyl oxidases are a family of enzymes that play a critical role in scar formation and maintenance. Lysyl oxidases stabilize the main component of scar tissue, collagen, and drive scar stiffness and appearance. Here we describe the development and characterisation of an irreversible lysyl oxidase inhibitor, PXS-6302. PXS-6302 is ideally suited for skin treatment, readily penetrating the skin when applied as a cream and abolishing lysyl oxidase activity. In murine models of injury and fibrosis, topical application reduces collagen deposition and cross-linking. Topical application of PXS-6302 after injury also significantly improves scar appearance without reducing tissue strength in porcine injury models. PXS-6302 therefore represents a promising therapeutic to ameliorate scar formation, with potentially broader applications in other fibrotic diseases.

Suggested Citation

  • Nutan Chaudhari & Alison D. Findlay & Andrew W. Stevenson & Tristan D. Clemons & Yimin Yao & Amar Joshi & Sepidar Sayyar & Gordon Wallace & Suzanne Rea & Priyanka Toshniwal & Zhenjun Deng & Philip E. , 2022. "Topical application of an irreversible small molecule inhibitor of lysyl oxidases ameliorates skin scarring and fibrosis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33148-5
    DOI: 10.1038/s41467-022-33148-5
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