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
D Noël
Université de Montpellier
Meet the team
Université de Montpellier
Université de Montpellier
Université Pierre et Marie Curie
Université Pierre et Marie Curie
Hospital Teresa Herrera
Arthritis Courtin Fondation
Université de Nantes
Université de Nantes
Centre Universitaire des Saints-Pères
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
- Yassin Tachikart, Olivier Malaise, Marcus Mumme, Christian Jorgensen, Jean-Marc Brondelloa (2019) Seno-suppressive molecules as new therapeutic perspectives in rheumatic diseases. DOI=10.1016/j.bcp.2019.03.017
Read more - Vinatier C, Domínguez E, Guicheux J and Caramés B (2018) Role of the Inflammation-Autophagy-Senescence Integrative Network in Osteoarthritis. Front. Physiol. 9:706. DOI=10.3389/fphys.2018.00706
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