Inhibition of CD40-TRAF6 interactions appaers a potent and selective therapeutic targeting strategy for treating cardiovascular disease.
The interaction between the different immune cells, and the (subsequent) secretion of immune-regulatory and activating cytokines and chemokines determines the progression of atherosclerosis. Key players in modulating these complex immune interactions and responses are the group of co-stimulatory molecules. The group of Prof. Lutgens (LMU) et al found that inhibition of the co-stimulatory molecules CD40L and CD40 is highly effective in reducing atherosclerosis, and in transforming dangerous vulnerable plaques into beneficial stable plaques. CD40L and CD40 antagonists are therefore known as the most potent plaque preventers and stabilizers in a laboratory setting. Although CD40 and CD40L blocking antibodies are used in phase 2 trials for cancer, multiple sclerosis and Crohn’s disease, long-term treatment with these antibodies, as is needed for the treatment of atherosclerosis is not feasible, because of the well -known risk of immunosuppression. Therefore, targeting of CD40 signaling intermediates that leaves some of the CD40-signalling intact to preserve immunity is the preferred strategy.
A patent (WO 2014/033122 A1), with E. Lutgens, C. Weber and G. Nicolaes as inventors has been filed by and has recently been approved in the US and EU, patent numbers US 9,408,289 and EP12 181 862.9 respectively.
Full results of this collaborative action are published in the Journal of the American College of Cardiology and can be found here or https://doi.org/10.1016/j.jacc.2017.11.055