Network pharmacology drug repurposing strategy for neurovascular diseases

Stroke is currently the third cause of death and first of disability in industrialized countries. However, translational stroke research has yielded only one thrombolytic and no neuroprotective therapy over the last decades. In fact, only single-drug targets were hitherto pursued leading to no patient benefit and thus obstructing innovation in the most profound manner. Contrary, we now know that complex diseases are defined by multitarget modules of dysregulated genes causing different pathophysiological scenarios. Therefore, we now propose an in silico-based multitarget approach based on human disease genes linked to further identify mechanistically-related potential targets which could be then pharmacologically modulated following a network pharmacology therapeutic approach. Indeed, network pharmacology exploits this concept by simultaneously targeting several components of a disease module, combining mechanistically related and therefore synergistic drugs. This (i) allows to reduce the dose of each drug, (ii) thereby decreases potential side-effects, and (iii) through synergy enhances the full therapeutic effect. Additionally, to maximally speed-up market entry, we aim to follow a drug repurposing strategy which ensures therapeutic safety and quick access to the pharmaceutic market. Altogether, we propose a mechanism-based therapy targeting the underlying cause of the disease being modulated by a safe, easily translational therapeutic approach for patient suffering from neurovascular diseases.