The overall aim of our research is to improve clinical treatment of systemic inflammatory diseases using extracellular HMGB1 neutralization as a novel therapeutic strategy.
We discovered the nuclear protein HMGB1 as the prototypical alarmin molecule acting as an endogenous May-day signal released from any stressed cell in animals and plants. Preclinical studies of HMGB1 antagonists are highly relevant for future clinical studies since the HMGB1 protein is 99% identical in mammals.
Our present aims are:
- To develop HMGB1-neutralizing Affibody®-molecules for therapeutic studies in stroke in an EU-FP7-sponsored project, that we co-ordinate.
- To bring our recently humanized anti-HMGB1 mAb to toxicology studies in order to get to clinical therapeutic studies. The mAb performs remarkably well in multiple HMGB1-dependent sterile and infectious disease models.
- To elucidate the effector mechanism for recombinant HMGB1 box A protein, a potent HMGB1 antagonist with highly beneficial effects in many experimental models of inflammatory diseases. Revealing the mode of action will enable a design of presently non-existing in vitro assays for functional box A analysis. This is a necessary step for bringing the recombinant box A domain to clinical trials.