Long-term effects of edaravone on survival of patients with amyotrophic lateral sclerosis

Abstract

Background and purposeOxidative stress has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Edaravone, a free radical scavenger, was approved as a therapeutic drug for ALS in 2015 in Japan. A phase 3 clinical trial demonstrated a smaller decline in ALS functional scale scores compared with placebo. However, the long-term effects of edaravone on ALS patients remain unclear. This study aimed to retrospectively investigate the long-term effects of edaravone on the survival of ALS patients.MethodsWe retrospectively analyzed 27 consecutive patients with ALS who were treated with edaravone and 30 consecutive ALS patients who were not treated with edaravone between 2010 and 2016.ResultsThe differences of ALSFRS-R scores from baseline to 6 months was significantly reduced in the edaravone group, compared to the control group. The changes in serum creatinine, as a possible marker of ALS severity, from baseline to 6 and 12 months were significantly improved in the edaravone group, compared to the control group. The survival rate was significantly improved in the edaravone group compared with control patients.ConclusionOur retrospective single-center analysis suggests slower progression and better prognosis of ALS patients with edaravone treatment. Further investigation, including prospective multicenter analysis, is warranted to confirm the usefulness of edaravone for a better prognosis of ALS.

Mitochondrial Permeability Transition: A Molecular Lesion with Multiple Drug Targets

“…Clinical success of edaravone: The first phase III studies edaravone demonstrated reduction of revised ALS functional rating scale (ALSFRS-R) over placebo group and efficacy in ALS, however only in early-stage disease [10]. These data were confirmed in a second randomized, double-blinded, placebo-controlled trial [129].…”

“…However, in the last 5 years, multiple groups have identified several novel, chemically distinct small molecule inhibitors of the mPTP, opening avenues for drug discovery and development that will have wide therapeutic potential. Most notably, edaravone (Radicut™), a potent anti-oxidant and inhibitor of the permeability transition has been approved for the treatment of amyotrophic lateral sclerosis (ALS) [10] as well as there being early successes in the treatment of the collagenopathies [11][12][13].…”

“…A number of alternative approaches for mPTP inhibition have been reported, probably acting via inhibiting pathways upstream to mPTP opening, including modulation of mitochondrial redox state [10,82,83], ETC function [84] and Ca 2+ influx (REF). The most significant achievement to date is the approval of Edaravone (Radicut™) [10] (Box 2), a potent anti-oxidant and inhibitor of mPTP opening and having demonstrated protection in multiple models [85,86]. The mitochondrial targeted antioxidant (AntiOxBEN3), targeted to mitochondria by conjugation with triphenylphosphonium (TPP + ), delayed Ca 2+ -induced mPTP opening and protected against iron-and hydrogen peroxide-induced cytotoxicity [82].…”

Antioxidant Alternatives in the Treatment of Amyotrophic Lateral Sclerosis: A Comprehensive Review

“…Edaravone is a low-molecular-weight antioxidant drug (Radicava R ), administered intravenously (Petrov et al, 2017) which acts as a free radical scavenger (Jackson et al, 2019) ( Table 1). In 2015, edaravone was approved for ALS treatment in Japan (Okada et al, 2018) and by the Food and Drug Administration of United States in 2017 (Watanabe et al, 2018).…”

Bidens pilosa Extract Administered after Symptom Onset Attenuates Glial Activation, Improves Motor Performance, and Prolongs Survival in a Mouse Model of Amyotrophic Lateral Sclerosis

“…Thus, an effective model to study the behavior of ALS observed in the majority of ALS patients has not been devised. Although edaravone and riluzole are currently available for ALS treatment, post symptomatic administration provides only limited effects on survival [29,30]. In fact, riluzole treatment significantly prolonged the survival of G93A mice by 7.5% compared to that of untreated G93A mice (untreated G93A mice: 126.1 days vs. riluzole-treated G93A mice: 135.5 days); however, treatment was initiated in 30-day-old mice [31].…”