Immune biomarker- and microRNA-guided dose escalation phase I clinical study of a RIG-Iigand for the treatment of multiple sclerosis

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In the first funding period we identified RIG-l-like receptors RLHs (RIG-I and MDA-5) as negative regulators of Th1/Th17 responses and uncovered a protective role of the corresponding ligands in multiple sclerosis. Based on these results we now aim at translating this experimental approach with a synthetic RIG-I ligand into the clinical setting in patients with multiple sclerosis. In preparation of a clinical trial with the synthetic RIG-I ligand we will first evaluate immunological biomarkers and the microRNA profile in the blood of healthy volunteers and of patients with multiple sclerosis receiving routine treatment with a standard dose of IFN-ß. Based on these results we will perform a clinical trial in which healthy volunteers receive increasing doses of RIGI ligand up to the biomarker level established in the first part and under additional guidance by the preclinical in vitro and in vivo results. This stepwise approach will allow to identify a safe and effective dose level (RIG-I ligand is a first in class, first in man, immunological) for subsequent testing of RIG-I ligand in a phase II efficacy trial. For this trial our expectation is that treatment with RIG-I ligand reaches at least the level of therapeutic activity of established IFN-ß treatment or higher.