Given the complexity of MS, it is noteworthy that H3R has been reported to play an important role in maintaining blood brain barrier integrity during neuroinflammation in a model of experimental autoimmune encephalomyelitis[33]; Consequently, H3R agonism has been proposed as a potential protective factor against MS progression.[34] Therefore in a clinical setting, the therapeutic window for H3R inverse agonist administration and target patient population should be carefully selected to avoid any potential side effect on blood brain barrier integrity. The gene discussed is HRH3; the disease is experimental autoimmune encephalomyelitis.