New experimental findings of LUNIRI were published in the journal Arthritis and Rheumatology
In the current publication we show that the topoisomerase I (topo I) inhibitor irinotecan and the tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitor furamidine in combination efficiently suppress lupus nephritis. While inhibitors of topo I stabilize the complex of topo I and DNA, the enzyme TDP1 releases topo I from the stalled complex. One previously known consequence of topo I inhibition is the prevention of DNA relaxation; this effect can be reverted by addition of TDP1. We demonstrated that these effects correlate with the binding of anti-dsDNA antibodies which are believed to be the main pathogen in systemic lupus erythematosus (SLE). We conclude from these data that DNA relaxation is crucial in the development of SLE and furthermore, changes in DNA relaxation by topo I and TDP1 inhibitors can be applied as entire new targeted therapy for this disease (Keil A. et al. Arthritis Rheumatol. 2015 Mar 16. doi: 10.1002/art.39119).
Congratulations to Andreas for his first publication as first author! Thanks to the team!