Our team at Oslo University Hospital and University of Oslo has found a potent immune regulatory microRNA harbouring a potential to treat inflammatory conditions. Osteoarthritis is a common inflammatory joint disease and the specific microRNA represents a novel disease modifying treatment strategy that can protect the cartilage from the destructive inflammatory response and prevent joint degradation.
Inven2 seeks collaboration with industrial partners and licensors who can support the continued development of a specific isoform of microRNA-140 (a so-called isomiR ) as a novel drug candidate for osteoarthritis. The drug candidate is currently in pre-clinical phase and in vivo testing in an osteoarthritis mouse model is ongoing; results expected in 2022. The drug candidate can also be relevant for other immune-related diseases like rheumatoid arthritis, Bechterew’s disease and psoriatic arthritis.
MicroRNAs (miRNAs) are small RNAs that regulate gene expression. They are potent regulatory molecules with interesting therapeutic potential and their repertoire is increasing in complexity with the emergence of deep sequencing data revealing numerous sequence variants, isomiRs, of microRNAs. MicroRNA-140 (miR-140) is considered to be a cartilage specific microRNA. Our team investigated the role of miR-140-3p and two of its isomiRs, a 5′ isomiR and a 3′ isomiR, in an inflammation-induced model of osteoarthritis. The three microRNAs downregulated many of the same genes. However, the 5′ isomiR showed a much greater target spectrum compared to the other two microRNAs. Introduction of the 5′ isomiR led to downregulation of genes essential for some of the most important inflammation cascades and virtual silencing of genes responsible for antigen presentation. The observations indicate a very promising therapeutic potential for the 5′ isomiR for osteoarthritis and other inflammatory conditions.
- Al-Modawi, R. N., Brinchmann, J. E., & Karlsen, T. A. (2021). Extensive Downregulation of Immune Gene Expression by MicroRNA-140-3p 5’isomiR in an In Vitro Model of Osteoarthritis. Osteoarthritis and Cartilage Open, 100189.
- Al-Modawi, R. N., Brinchmann, J. E., & Karlsen, T. A. (2019). Multi-pathway protective effects of microRNAs on human chondrocytes in an in vitro model of osteoarthritis. Molecular Therapy-Nucleic Acids, 17, 776-790.
A patent application has been filed.