New Therapeutics

Based on the information derived from multi-omics research, delivery of therapeutic nucleic acids is planned. Depending on the mechanism of action identified, either regulatory miRNA or mRNA coding for a therapeutic protein will be used^[1], [2]. These new therapeutics will be tested according to 3R principles in a human osteochondral ex vivo model that combines minor superficial structural damage with joint mimicking kinematic load[3]. This ex vivo model will illustrate that the AI platform is capable of generating clear and conclusive results. Nucleic acids will be delivered to full-thickness articular joint cartilage using an established peptide delivery system. The technology created on cmRNA delivery for bone regeneration (EU H2020 grant 874790) will be transferred to articular joint cartilage research. This previous experience demonstrates the feasibility of the approach.

The new European AI platform for clinical OA data enables better biobanking of blood, serum, and synovial samples for future research and biomarker diagnostics. Candidate patient samples will be stored for OA research, and analyses will be uploaded to the AI database. This follows our previous work on a multicenter cancer biobank with over 30 centers contributing samples (imodi-cancer.org), which now supports multiple European projects. The AI platform will identify patients with available samples for future research. Our biobank in Lyon, fully authorized for public and private use, is equipped to handle the project, offering significant cost advantages. We are at TRL level 8-9 for this aspect of the project.

References:

[1] Isenmann M, Stoddart MJ, Schmelzeisen R, Gross C, Della Bella E, Rothweiler M. Basic principles of RNA interference: Nucleic acid types and in vitro intracellular delivery methods. Micromachines 2023, 14, 1321.

[2] Della Bella E, Menzel U, Naros A, Kubosch EJ, Alini M, Stoddart MJ. Identification of circulating miRNAs as fracture-related biomarkers. PLoS ONE 2024:19(5): e0303035.

[3] Wen L, Grad S, Creemers LB, Stoddart MJ. Establishment of an ex vivo cartilage degeneration model by combined collagenase and aggrecanase treatment and mechanical loading. Research Square 2024.