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Updated: Nov 15, 2025

The Goeckerman Regimen for the Treatment of Moderate to Severe Psoriasis
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MTH1 Inhibitors for the Treatment of Psoriasis

Cecilia Bivik Eding1, Ines Köhler1, Deepti Verma1

  • 1Ingrid Asp Psoriasis Research Center, Division of Dermatology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

The Journal of Investigative Dermatology
|March 7, 2021
PubMed

Insights

Small-molecule inhibitors targeting MTH1 reduce oxidative stress and inflammation in psoriasis. MTH1 inhibition shows promise as a topical therapy by decreasing psoriatic characteristics and key inflammatory markers.

Area of Science:

  • Molecular Biology
  • Dermatology
  • Immunology

Background:

  • Inflammatory diseases like psoriasis involve altered redox regulation.
  • MTH1 enzyme prevents oxidized nucleotides from incorporating into DNA during replication.

Purpose of the Study:

  • To investigate the role of MTH1 in psoriasis pathogenesis.
  • To evaluate MTH1 small-molecule inhibitors as a potential therapeutic strategy for psoriasis.

Main Methods:

  • Utilized MTH1 small-molecule inhibitors in normal and malignant keratinocytes.
  • Analyzed MTH1 expression in lesional skin and PBMCs from psoriasis patients.
  • Employed the imiquimod psoriasis mouse model to assess therapeutic effects.
  • Measured cytokine levels and T cell populations in skin and lymph nodes.

Main Results:

  • MTH1 inhibition induced apoptosis via oxidized nucleotide accumulation and DNA damage.
  • Increased MTH1 expression was observed in psoriasis lesions and PBMCs.
  • Inhibition reduced psoriatic features, normalized immune cell levels, and decreased T helper type 17-associated cytokines.
  • MTH1 inhibition prevented IL-17 downstream gene upregulation in human keratinocytes.

Conclusions:

  • MTH1 inhibition effectively reduces key inflammatory pathways in psoriasis.
  • Small-molecule MTH1 inhibitors are a promising topical therapeutic approach for psoriasis.

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