Neuroprotective therapy both for als and acute ischemic stroke

Abstract

Although the underlying mechanism of amyotrophic lateral sclerosis (ALS) has not yet been fully clarified, several reports have implicated the involvement of oxidative stress under selective death of motor neurons in both ALS patients and animal models. Edaravone is a free radical scavenger, which is the first clinical drug for neuroprotection in the world which has been approved from 2001 in most ischemic stroke patients in Japan, and some of China and India. A recent multicenter prospective double-blind placebo-control clinical trial with edaravone for ALS patients conducted in Japan showed a positive effect for delaying the clinical score (ALS FRS-R) during the 24 weeks of examination. This clinical benefit of edaravone was shown as an add-on therapy after anti-glutamatergic riluzole. These data strongly suggest a potential underlying mechanism of oxidative stress in ALS and a clinical delay by a free radical scavenger. These translational studies on a free radical scavenger Edaravone allowed governmental permissions both for acute ischemic stroke after 2001 and for ALS after 2015. Edaravone was approved for ALS at 2015 in Japan, 2016 in Korea, and 2017 in USA. Use of Edaravone greatly reduced hemorrhagic transformation accompanied by tissue plasminogen activator (tPA) treatment, and may also extend therapeutic time window with tPA therapy for more than 4.5 h in human stroke patients for preserving neurovascular unit (NVU). An intensive Edaravine therapy for 3 days now showed a favorite recovery in 3 European countries.