EDARAVONE: A NEW APPROACH TO TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS
Keywords:
Amyotrophic lateral sclerosis, edaravone, oxidative damage, mechanism of actionAbstract
Amyotrophic lateral sclerosis (ALS) is a fatal progressive disease of the central nervous system with damage to the upper and lower motor neurons and leading to severe disability and death 3-5 years after its debut (1).Until 2017, riluzole was the only approved medication for patients with ALS, offering a limited survival benefit of about 3–5 months.(2) In 2017, the FDA approved another drug for the treatment of ALS - edaravone (trade names: radicut, radicava, aron, ceravon).(3) The drug acts as a strong antioxidant, destroying lipid peroxidation products (LPOP) and hydroxyl radicals. As with riluzole, the exact mechanism of action of edaravone is not clear. The drug is thought to mitigate oxidative damage to neurons and glia (accessory cells in nerve tissue) that are at risk in ALS. In a phase III clinical study of the drug in Japan, 137 patients with an early stage of ALS development participated. Edaravone has been shown to be effective in suppressing the deterioration of motor function in these patients. Although in the USA edaravone was approved for the treatment of all patients with ALS, it was recommended to use it in the early stages of the disease, within 2 years from the date of debut in patients with a forced vital capacity of more than 80%.( 4). There are no data on the effectiveness of edaravone in the wider population of ALS patients. A study of the effectiveness of this drug with an assessment of survival is ongoing. In view of the above, the development of new approaches to ALS therapy remains an urgent problem.
References
I. S.Bakulin, A.V. Worms, 2017.
Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic
lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med 1994;330:585-91.
Miyaji Y., Yoshimura S., Sakai N. et al. Effect of edaravone on favorable outcome in patients with acute cerebral large vessel occlusion: subanalysis of RESCUE-Japan registry. Neurol Med Chir (Tokyo) 2015;55(3):241–7. DOI: 2176/nmc. ra.20140219. PMID: 25739433.
Abe K., Aoki M., Tsuji S. et al. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurology 2017;16(7):505–12. DOI: 10.1016/S14744422(17)30115-1. PMID: 28522181.
Zarei S, Car r K, Reiley L, Diaz K, Guerra O, Altamirano PF,et al. A comprehensive review of amyotrophic lateral sclerosis. Surg Neurol Int. 2015;6:171. (https://www.accessdata.fda.gov/drugsatfda_docs/ label/2017/209176lbl.pdf
Suponeva N. A., Piradov M. A. 2013, Zavalishin I. A., Piradov M.A., Boyko A.N. 2014].
Chio A.G., Traynor B.J, Logroscino G., et al. 2013.
Parakh S, Spencer DM, Halloran MA, Soo KY, Atkin JD.Redox regulation in amyotrophic lateral sclerosis. Oxid Med Cell Longev. 2013;2013:408681.
. D’Amico E, Factor-Litvak P, Santella RM, Mitsumoto H.Clinical perspective on oxidative stress in sporadic amyotrophic lateral sclerosis. Free Radic Biol Med. 2013;65:509–27.
Murata T, Ohtsuka C, Terayama Y. Increased mitochondrial oxidative damage in patients with sporadic amyotrophic lateral sclerosis. J Neurol Sci. 2008;267:66–9.
Mitsumoto H, Santella RM, Liu X, Bogdanov M, Zipprich J, Wu HC, et al. Oxidative stress biomarkers in sporadic ALS. Amyotroph Lateral Scler. 2008;9:177–83.
Bogdanov M, Brown RH, Matson W, Smar t R, Hayden D,O’Donnell H, et al. Increased oxidative damage to DNA inALS patients. Free Radic Biol Med. 2000;29:652–8.
Blasco H, Garcon G, Patin F, Veyrat-Durebex C, Boyer J, Devos D, et al. Panel of oxidative stress and inflammatory biomarkers in ALS: a pilot study. Can J Neurol Sci.
. Simpson EP, Henr y YK, Henkel JS, Smith RG, Appel SH. Increased lipid peroxidation in sera of ALS patients: a potential biomarker of disease burden. Neurology. 2004;62:1758–65.
Baillet A, Chanteperdrix V, Trocme´ C, Casez P, Garrel C, Besson G. The role of oxidative stress in amyotrophic lateral sclerosis and Parkinson’s disease. Neurochem Res. 2010;35:1530–7
Tohgi H, Abe T, Yamazaki K, Murata T, Ishizaki E, Isobe C.Remarkable increase in cerebrospinal fluid 3-nitrotyrosine in patients with sporadic amyotrophic lateral sclerosis. Ann Neurol. 1999;46:129–31.
Beal MF, Ferrante RJ, Browne SE, Matthews RT, Kowall NW, Brown RH Jr. Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis. Ann Neurol. 1997;42:644–54.
LoGerfo A, Chico L, Borg ia L, Petrozzi L, Rocchi A,D’Amelio A, et al. Lack of association between nuclear factor er ythroid-derived 2-like 2 promoter gene polymorphisms and oxidative stress biomarkers in amyotrophic lateral sclerosis patients. Oxid Med Cell Longev.2014;2014:432626.
Pasquinelli A, Chico L, Pasquali L, Bisordi C, Lo Gerfo A, Fabbrin i M, et al. Gly482Ser PGC-1 a gene polymorphism and exercise-related oxidative stress in amyotrophic lateral sclerosis patients. Front Cell Neurosci. 2016;10:102.
The Edaravone Acute Brain Infarction Study Group (Chair:Otomo E). Effect of a novel free radical scavenger, edaravone (MCI-186), on acute brain infarction. Randomized, placebo-controlled, double-blind study at multicenters.Cerebrovasc Dis. 2003;15:222–9.
National Institute of Neurological Disorders and Stroke. Amyotrophic Lateral Sclerosis (ALS) fact sheet. National Institutes of Health. Updated June 20, 2020. Accessed May 20, 2021. https://www.ninds.nih.gov/ Disorders/Patient-Caregiver-Education/Fact-Sheets/Amyotrophic-Lateral-Sclerosis-ALS-Fact-Sheet
American Academy of Neurology. AAN summary of evidence-based guideline for clinicians: The care of the patient with amyotrophic lateral sclerosis: drug, nutritional and respiratory therapies. American Academy of Neurology. Updated January 11, 2020. Accessed May 20, 2021. https://www.aan.com/ Guidelines/home/GuidelineDetail/370
Miller RG, Brooks BR, Swain-Eng RJ, et al. Quality improvement in neurology: Amyotrophic lateral sclerosis quality measures: Report of the quality measurement and reporting subcommittee of the American Academy of Neurology. Neurology. 2013;81(24):2136-40. doi:10.1212/01.wnl.0000437305.37850.f9
Miller RG, Jackson CE, Kasarskis EJ, et al. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009;73(15):1227-33. doi:10.1212/WNL.0b013e3181bc01a4
Yamamoto Y, Kuwahara T, Watanabe K, Watanabe K. Antioxidant activity of 3-methyl-1-phenyl-2-pyrazolin-5-one. Redox Rep. 1996;2:333–8.
Abe S, Kirima K, Tsuchiya K, Okamoto M, Hasegawa T, Houchi H, et al. The reaction rate of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186)) with hydroxyl radical. Chem Pharm Bull. 2004;52:186–91.
Kamogawa E, Sueishi Y. A multiple free-radical scavenging
(MULTIS) study on the antioxidant capacity of a neuroprotective drug, edaravone as compared with uric acid,glutathione, and trolox. Bioorg Med Chem Lett.2014;24:1376–9.
Fujisawa A, Yamamoto Y. Edaravone, a potent free radicalscavenger, reacts with peroxynitrite to produce predominantly 4-NO-edaravone. Redox Rep. 2016;21:98–103.
