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

Tahvili, Sahar LU ; Törngren, Marie ; Holmberg, Dan LU ; Leanderson, Tomas LU and Ivars, Fredrik LU (2018) In PLoS ONE 13(5).
Abstract

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... (More)

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.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
13
issue
5
article number
e0196598
publisher
Public Library of Science (PLoS)
external identifiers
  • scopus:85046735389
  • pmid:29742113
ISSN
1932-6203
DOI
10.1371/journal.pone.0196598
language
English
LU publication?
yes
id
55baab18-4a35-46ff-91d1-d8e9741920ea
date added to LUP
2018-05-24 13:36:12
date last changed
2024-03-01 19:38:42
@article{55baab18-4a35-46ff-91d1-d8e9741920ea,
  abstract     = {{<p>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 Ly6C<sup>hi</sup> 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.</p>}},
  author       = {{Tahvili, Sahar and Törngren, Marie and Holmberg, Dan and Leanderson, Tomas and Ivars, Fredrik}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{5}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Paquinimod prevents development of diabetes in the non-obese diabetic (NOD) mouse}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0196598}},
  doi          = {{10.1371/journal.pone.0196598}},
  volume       = {{13}},
  year         = {{2018}},
}