SEN-OA – Targeting senescent cells in osteoarthritis: an innovative therapeutic approach

Concept

The main risk factor for Osteoarthritis (OA) is ageing. An emerging concept for age-related diseases is that senescent cells accumulate with time and release SASP (senescence-associated secretory profile) products, which alter tissue functions. Accumulation of senescent cells during lifespan is believed to contribute to progressive tissue loss of functions. Specific elimination of these cells could prevent some age-associated diseases.

Facts and figures

Project lead
PhD D Noël
Université de Montpellier
daniele.noel@inserm.fr
FOREUM research grant: € 600.000
2018 - 2021

Meet the team

PhD D Noël
Université de Montpellier
MD, PhD C Jorgensen
Université de Montpellier
PhD X Houard
Université Pierre et Marie Curie
Pharm.D, PhD C Caramés Perez
Hospital Teresa Herrera
Mr. L Comole
Arthritis Courtin Fondation
PhD J Guicheux
Université de Nantes
PhD C Vinatier
Université de Nantes
MD, PhD F Rannou
Centre Universitaire des Saints-Pères
PhD P van der Kraan
Radboud UMC

Objectives

We propose a multifaceted approach combining innovative biomedical senescence models, ageing animal studies, human sample analyses and screening for senescence-targeting compounds for clinical application to (i) decipher the role of ageing-associated senescence mechanisms in the appearance of OA and (ii) develop innovative treatments for OA patients. If successful, the project could lead to a first- in-man clinical trial.

Patient voice

We have discussed the proposal with a patient group in Paris, they thought the idea novel and worthwhile. We gained their input to the lay summary. We will have two patient representatives to support the writing of our patient information sheets and to help communicate the findings of the project. They will participate to the scientific advisory board. There are no obvious risks of the project to the patients. Technical risk is minimal as the assays involved are already carried out in our laboratories.

Interim results

WP1. A movie dedicated to the presentation of the SEN-OA project and to the feedback of two patient experts of one-day visit of a research laboratory on OA has been made.

WP2. Several types of samples in 3 non-clinical models of mice and humans with OA have been collected and are under evaluation for expression of senescence markers in various articular tissues.

WP3. Different in vitro (stem cells, chondrocytes) and in vivo (mouse, zebrafish) models of senescence have been developed. Senolytics are being evaluated in those models.  

WP4. A preliminary screening was performed with a repurposing library to identify Senolytics and Pro-autophagy modulators in human chondrocytes. Several candidates are available for further validation.

Publications

Vinatier C, Domínguez E, Guicheux J and Caramés B (2018) Role of the Inflammation-Autophagy-Senescence Integrative Network in Osteoarthritis. Front. Physiol. 9:706. https://doi.org/10.3389/fphys.2018.00706
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Yassin Tachikart, Olivier Malaise, Marcus Mumme, Christian Jorgensen, Jean-Marc Brondelloa (2019) Seno-suppressive molecules as new therapeutic perspectives in rheumatic diseases. https://doi.org/10.1016/j.bcp.2019.03.017
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