Toward Effective Combination Therapy and Pleiotropic Drugs

Abstract

Acute ischaemic stroke is a major cause of morbidity and mortality. The most effective treatment is early reperfusion, although less than half of patients who are finally treated obtain permanent benefits. The combination of rapid reperfusion and neuroprotective therapies would be of added value for maximizing the beneficial effects of rapid reperfusion and to reduce the harmful consequences of reperfusion injury, including the no-reflow phenomenon, after recanalization. Given the relevance of oxidative stress in the physiopathology of brain ischaemia, the use of antioxidant molecules, such as uric acid, could translate into effective neuroprotective effects. Uric acid is the most potent natural antioxidant, and its exogenous administration is neuroprotective and has synergistic effects when administered alongside alteplase, a thrombolytic drug. In humans, uric acid therapy is safe and has measurable neuroprotective effects, especially in patients with pre-treatment hyperglycaemia or in women. Given the encouraging preclinical and clinical data regarding the potential neuroprotective effects of uric acid administration in combination with reperfusion in acute brain ischaemia, the development of adequately powered pivotal confirmatory clinical trials is warranted.