Drug Repurposing: Promises of Edaravone Target Drug in Traumatic Brain Injury

Shakkour, Zaynab; Issa, Hawraa; Ismail, Helene; Ashekyan, Ohanes; Habashy, Karl John; Nasrallah, Leila; Jourdi, Hussam; Hamade, Eva; Mondello, Stefania; Sabra, Mirna; Zibara, Kazem; Kobeissy, Firas

doi:10.2174/0929867327666200812221022

Cited by 20 publications

(17 citation statements)

References 142 publications

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“…It has been approved in Japan for ALS treatment since 2015 and in the United States since 2017 ( Lapchak, 2010 ; Voelker, 2017 ). There have been several additional studies to evaluate the therapeutic efficacy of edaravone in other diseases, including traumatic brain injury and optic nerve injury, among others ( Akiyama et al, 2017 ; Bailly, 2019 ; Shakkour et al, 2021 ). One such investigation found a moderate reduction (approximately 50% for creatinine and BUN) of AKI in a rat model of cisplatin-induced AKI ( Iguchi et al, 2004 ).…”

Section: Discussionmentioning

confidence: 99%

Kidney-Targeted Redox Scavenger Therapy Prevents Cisplatin-Induced Acute Kidney Injury

et al. 2022

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Cisplatin-induced acute kidney injury (CI-AKI) is a significant co-morbidity of chemotherapeutic regimens. While this condition is associated with substantially lower survival and increased economic burden, there is no pharmacological agent to effectively treat CI-AKI. The disease is hallmarked by acute tubular necrosis of the proximal tubular epithelial cells primarily due to increased oxidative stress. We investigated a drug delivery strategy to improve the pharmacokinetics of an approved therapy that does not normally demonstrate appreciable efficacy in CI-AKI, as a preventive intervention. In prior work, we developed a kidney-selective mesoscale nanoparticle (MNP) that targets the renal proximal tubular epithelium. Here, we found that the nanoparticles target the kidneys in a mouse model of CI-AKI with significant damage. We evaluated MNPs loaded with the reactive oxygen species scavenger edaravone, currently used to treat stroke and ALS. We found a marked and significant therapeutic benefit with edaravone-loaded MNPs, including improved renal function, which we demonstrated was likely due to a decrease in tubular epithelial cell damage and death imparted by the specific delivery of edaravone. The results suggest that renal-selective edaravone delivery holds potential for the prevention of acute kidney injury among patients undergoing cisplatin-based chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Kidney-Targeted Redox Scavenger Therapy Prevents Cisplatin-Induced Acute Kidney Injury

et al. 2022

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“…As the first free radical scavenger for acute ischaemic stroke, edaravone (MCI‐186, 3‐methyl‐1‐phenyl‐2‐pyrazolin‐5‐one) is produced by Mitsubishi Tanabe Pharma Corporation (Japan). Edaravone was approved for sale in Japan in 2001 and has been widely accepted for clinical use in Japan, China and India 4 . Edaravone was first regarded to express a favourable performance in animal models of stroke in the late 1980s 5‐7 .…”

Section: What Is Known and Objectivementioning

confidence: 99%

“…Edaravone was approved for sale in Japan in 2001 and has been widely accepted for clinical use in Japan, China and India. 4 Edaravone was first regarded to express a favourable performance in animal models of stroke in the late 1980s. 5 , 6 , 7 There exist three underlying antioxidative mechanisms of edaravone.…”

Section: What Is Known and Objectivementioning

confidence: 99%

Clinical effects and safety of edaravone in treatment of acute ischaemic stroke: A meta‐analysis of randomized controlled trials

Chen

Lin

et al. 2021

J Clin Pharm Ther

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What is known and objective Edaravone is a new antioxidant and hydroxyl radical scavenger. Although there is evidence that it improves clinical outcomes of patients with acute ischaemic stroke (AIS), it is not yet widely accepted for treatment of AIS in Western countries. We further investigated the efficacy and safety of edaravone through this meta‐analysis of randomized controlled clinical trials (RCTs). Method Pubmed, Embase, Web of Science and Cochrane Library were screened up to December 2020 for original articles from SCI journals that published in English. RCTs that compared edaravone versus placebo or no intervention in adult patients and reported the efficacy or safety of edaravone were regarded as eligible. Mortality was regarded as the primary outcome and the improvement of neurological impairment was regarded as the secondary outcome. Safety evaluation was conducted according to the incidence of adverse events. Review Manager 5.3 was employed to perform the assessment of the risk of bias and data synthesis. The Cochrane risk of bias tool for randomized controlled trials was employed to assess the risk of bias. Results and discussion Seven randomized controlled trials with 2069 patients were included. For the incidence of mortality, the pooled RR for studies that evaluated edaravone after three‐month follow‐up was 0.55 (95% Cl, 0.43‐0.7, I2 = 0, P < 0.01). The pooled RR for improvement of neurological impairment at the three months follow‐up was 1.54 (95% CI, 1.27‐1.87, I2 = 0, P < 0.01) in four RCTs. On subgroup analysis of studies that were conducted in Asia, the RR was 1.56 (95% CI, 1.27‐1.90, I2 = 0%; P < 0.01); the pooled RR for studies that conducted in Europe was 1.32 (95% CI, 0.64‐2.72; P = 0.45); the pooled RR for studies that used edaravone for two weeks was 1.42 (95% CI, 1.10 to 1.83, I2 = 0%; P < 0.01); the pooled RR for studies that used edaravone for one week was 1.64 (95% CI, 1.24‐2.16, I2 = 0%; P < 0.01); the pooled RR for studies that conducted in patients with mean age equal to or over 60 years was 1.52 (95% CI, 1.24‐1.87, I2 = 0%; P < 0.01); and the pooled RR for studies that conducted in patients with mean age less than 60 was 1.80 (95% CI, 1.05‐3.08, I2 = 0%; P = 0.03). For the incidence of any treatment‐related adverse events, the pooled RR for studies that evaluated edaravone during treatment was 0.83 (95% CI, 0.51‐1.34, I2 = 0, P = 0.43). The difference of the incidence of any treatment‐related adverse events between two groups was not statistically significant. What is new and conclusion The limited studies indicate that edaravone can improve neurological impairment with a survival benefit at three‐month follow‐up, regardless of the mean age and course of treatment. It is worthy of promotion in the clinical treatment of AIS in Asian countries. More well‐designed RCTs with larger sample sizes are needed to determine the benefits of edaravone in patients from Western countries.

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“…Moreover, the upstream regulators of AMPK may also serve as excellent drug targets. For example, a new antioxidant drug (Edaravone) was recently approved for ALS (Cho and Shukla, 2020 ; Shakkour et al, 2021 ). Many natural antioxidants (such as curcumin, ginkgo biloba) have also been tested in preclinical studies and clinical trials of AD (Arslan et al, 2020 ).…”

Section: Conclusion Remarksmentioning

confidence: 99%

Contribution of Energy Dysfunction to Impaired Protein Translation in Neurodegenerative Diseases

Liu

Chern

2021

Front. Cell. Neurosci.

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Impaired energy homeostasis and aberrant translational control have independently been implicated in the pathogenesis of neurodegenerative diseases. AMP kinase (AMPK), regulated by the ratio of cellular AMP and ATP, is a major gatekeeper for cellular energy homeostasis. Abnormal regulation of AMPK has been reported in several neurodegenerative diseases, including Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). Most importantly, AMPK activation is known to suppress the translational machinery by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1), activating translational regulators, and phosphorylating nuclear transporter factors. In this review, we describe recent findings on the emerging role of protein translation impairment caused by energy dysregulation in neurodegenerative diseases.

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Drug Repurposing: Promises of Edaravone Target Drug in Traumatic Brain Injury

Cited by 20 publications

References 142 publications

Kidney-Targeted Redox Scavenger Therapy Prevents Cisplatin-Induced Acute Kidney Injury

Kidney-Targeted Redox Scavenger Therapy Prevents Cisplatin-Induced Acute Kidney Injury

Clinical effects and safety of edaravone in treatment of acute ischaemic stroke: A meta‐analysis of randomized controlled trials

Contribution of Energy Dysfunction to Impaired Protein Translation in Neurodegenerative Diseases

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