Development of an antisense therapy for a novel target for Rheumatoid arthritis

Purpose and goal

The project aimed to develop specific anti-sense oligonucleotides (ASOs) that could reduce the amount of a specific protein in mice that Ulrika Norin demonstrated is driving the development of autoimmune disease. With the help of these ASOs, the plan was then to test this in autoimmune models to see if it would reduce joint rheumatism. The goal of identifying and testing ASOs according to plan has been achieved.

Expected results and effects

The project has identified three ASOs that significantly reduced the amount of the target protein in immune cells. One of these also showed a suppression of the target protein in the liver, kidneys and synovium and showed no signs of toxicity. It was tested in an arthritis model where it showed no signs of improvement of the disease. Studies are now underway in a similar arthritis model. At the same time, the project has taking advantage of the large effect in liver, identified a new indication autoimmune hepatitis where studies are now planned.

Planned approach and implementation

The project has been a collaboration between three parties, Karolinska Institutet, Secarna and Immunscape where the different parties would contribute their respective specialties. The plan was defined with clear responsibilities in the proposal and was followed during the project. Meetings have taken place through a number of personal meetings between the three project participants in Stockholm and Munich, respectively, combined with frequent organized telephone conferences and. The cooperation has worked very well.