A new therapeutic strategy for inhibiting pro-inflammatory macrophages in pre-clinical models of rheumatoid arthritis: using antagomir-155 encapsulated in pegylated liposomes

Concept

In RA patients, an increased expression of miR-155 in monocytes/macrophages could be responsible for impaired maturation of monocytes into M2 anti-inflammatory macrophages. Our aim is to assess if the defect of M2 polarization and the impact of miR-155 and others microRNA in this defect are present in 2 pre-clinical models of RA: the CIA and STIA mice.

Facts and Figures

Project Lead
A Paoletti
Paris-Saclay University
audreypaoletti@gmail.com
FOREUM research grant: €50,000
2020 - 2021

Meet the Team

A Paoletti
Paris-Saclay University
X Mariette
Hôpitaux Universitaire Paris-Sud
M Kurowska-Stolarska
University of Glasgow
I McInnes
University of Glasgow

Objectives

To demonstrate in mice model of rheumatoid arthritis (RA) that microRNA could be responsible of polarization of monocytes in pro-inflammatory macrophages in order to find a new safe treatment of RA specific of these cells.

Patient Voice

microRNA inhibition by another molecule is already in progress in some cancer with an apparent good safety profile. If we confirm efficacy and specificity of our treatment in mice models of arthritis, this approach could emerge as a novel and possible treatment for rheumatoid arthritis patients. Moreover our therapeutic strategy uses a new way for addressing the possible new drug directly in the macrophages infiltrating the joints and thus, should be devoid of side effects

Goals/Milestones

• First phase, validate new miR by classical PCR and study in vitro the effect of RA monocytestransfection on M2 polarization.
• Second phase, study in vivo on CIA and STIA mice monocytes polarization in M2 macrophages as compared to wild type mice.
• Third phase, determine in vivo on CIA and STIA mice monocytes polarization in M2 macrophages with or without injection of PEG-liposomes containing antagomiR-control or 155 and off-target” effect of injection of PEG-liposomes containing antagomiR-155 in other immunes cells.