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Dan Holmberg

Professor

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Paquinimod prevents development of diabetes in the non-obese diabetic (NOD) mouse

Author

  • Sahar Tahvili
  • Marie Törngren
  • Dan Holmberg
  • Tomas Leanderson
  • Fredrik Ivars

Summary, in English

Quinoline-3-carboxamides (Q compounds) are immunomodulatory compounds that have shown efficacy both in autoimmune disease and cancer. We have in here investigated the impact of one such compound, paquinimod, on the development of diabetes in the NOD mouse model for type I diabetes (T1D). In cohorts of NOD mice treated with paquinimod between weeks 10 to 20 of age and followed up until 40 weeks of age, we observed dose-dependent reduction in incidence of disease as well as delayed onset of disease. Further, in contrast to untreated controls, the majority of NOD mice treated from 15 weeks of age did not develop diabetes at 30 weeks of age. Importantly, these mice displayed significantly less insulitis, which correlated with selectively reduced number of splenic macrophages and splenic Ly6Chi inflammatory monocytes at end point as compared to untreated controls. Collectively, these results demonstrate that paquinimod treatment can significantly inhibit progression of insulitis to T1D in the NOD mouse. We propose that the effect of paquinimod on disease progression may be related to the reduced number of these myeloid cell populations. Our finding also indicates that this compound could be a candidate for clinical development towards diabetes therapy in humans.

Department/s

  • Immunology
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year

2018-05-01

Language

English

Publication/Series

PLoS ONE

Volume

13

Issue

5

Document type

Journal article

Publisher

Public Library of Science

Topic

  • Immunology in the medical area
  • Endocrinology and Diabetes

Status

Published

Research group

  • Immunology

ISBN/ISSN/Other

  • ISSN: 1932-6203