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Kutlubaev M.A.

Bashkir State Medical University

Promising approaches to the pathogenetic therapy of amyotrophic lateral sclerosis

Authors:

Kutlubaev M.A.

More about the authors

Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2024;124(4): 13‑21

DOI: 10.17116/jnevro202412404113

Read: 3843 times

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Table of contents

PROMISING APPROACHES TO THE PATHOGENETIC THERAPY OF AMYOTROPHIC LATERAL SCLEROSIS
PROMISING APPROACHES TO THE PATHOGENETIC THERAPY OF AMYOTROPHIC LATERAL SCLEROSIS

To cite this article:

Kutlubaev MA. Promising approaches to the pathogenetic therapy of amyotrophic lateral sclerosis. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;124(4):13‑21. (In Russ.)
https://doi.org/10.17116/jnevro202412404113

Подписка 2026 Журнал неврологии и психиатрии им. С.С. Корсакова (S.S. Korsakov Journal of Neurology and Psychiatry)
МСФ на ЯМ
Использование инфографики авторами научных работ
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Abstract:

Amyotrophic lateral sclerosis is a severe incurable disease of the nervous system. Currently only methods of palliative care for the patients with this disease are available. Few medications for the pathogenetic therapy are registered in some countries, i.e. riluzole, edaravon, sodium phenylbutyrate/taurursodiol as well as tofersen (conditionally). Their efficacy is relatively low. The main directions in the development of pathogenetic therapy of ALS include gene therapy, use of stem cells, immunomodulators, agents affecting gut microbiota. A search is also underway for low-molecular compounds with neuroprotective and antioxidant properties. Perspective direction is prevention of ALS. This will be possible when biomarkers for identification of patients in pre-manifest/prodromal stage are detected.

Keywords:

amyotrophic lateral sclerosis
motor neuron disease
treatment
prevention

Authors:

Kutlubaev M.A.

Bashkir State Medical University

Received:

28.09.2023

Accepted:

14.10.2023

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References:

  1. Younger DS, Brown RH Jr. Amyotrophic lateral sclerosis. Handb Clin Neurol. 2023;196:203-229.  https://doi.org/10.1016/B978-0-323-98817-9.00031-4
  2. Muzio L, Ghirelli A, Agosta F, et al. Novel therapeutic approaches for motor neuron disease. Handb Clin Neurol. 2023;196:523-537.  https://doi.org/10.1016/B978-0-323-98817-9.00027-2
  3. Dharmadasa T, Kiernan MC. Riluzole, disease stage and survival in ALS. Lancet. Neurol. 2018;17(5):385-386.  https://doi.org/10.1016/S1474-4422(18)30091-7
  4. Keifer OP Jr, Gutierrez J, Butt MT, et al. Spinal cord and brain concentrations of riluzole after oral and intrathecal administration: A potential new treatment route for amyotrophic lateral sclerosis. PLoS One. 2023;18(8):e0277718. https://doi.org/10.1371/journal.pone.0277718
  5. Jiang J, Wang Y, Deng M. New developments and opportunities in drugs being trialed for amyotrophic lateral sclerosis from 2020 to 2022. Front Pharmacol. 2022;13:1054006. https://doi.org/10.3389/fphar.2022.1054006
  6. Shen Y, Zhang J, Xu Y, et al. Ultrasound-enhanced brain delivery of edaravone provides additive amelioration on disease progression in an ALS mouse model. Brain Stimul. 2023;16(2):628-641.  https://doi.org/10.1016/j.brs.2023.03.006
  7. Pattee GL, Genge A, Couratier P, et al. Oral edaravone — Introducing a Flexible Treatment Option for Amyotrophic lateral sclerosis. Expert Rev Neurother. 2023;23(10):859-866.  https://doi.org/10.1080/14737175.2023.2251687
  8. Doble A. The pharmacology and mechanism of action of riluzole. Neurology. 1996;47(6 vyp 4):S233-41. PMID: 8959995. https://doi.org/10.1212/wnl.47.6_suppl_4.233s
  9. Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 2012;2012(3):CD001447. https://doi.org/10.1002/14651858.CD001447.pub3
  10. Cho H, Shukla S. Role of Edaravone as a Treatment Option for Patients with Amyotrophic Lateral Sclerosis. Pharmaceuticals (Basel). 2020;14(1):29.  https://doi.org/10.3390/ph14010029
  11. Jami MS, Salehi-Najafabadi Z, Ahmadinejad F, et al. Edaravone leads to proteome changes indicative of neuronal cell protection in response to oxidative stress. Neurochem Int. 2015;90:134-141.  https://doi.org/10.1016/j.neuint.2015.07.024
  12. Liu Z, Yang C, Meng X, et al. Neuroprotection of edaravone on the hippocampus of kainate-induced epilepsy rats through Nrf2/HO-1 pathway. Neurochem Int. 2018;112:159-165.  https://doi.org/10.1016/j.neuint.2017.07.001
  13. Gao M, Zhu L, Chang J, et al. Safety and Efficacy of Edaravone in Patients with Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-analysis. Clin Drug Investig. 2023;43(1):1-11.  https://doi.org/10.1007/s40261-022-01229-4
  14. Paganoni S, Macklin EA, Hendrix S, et al. Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis. N Engl J Med. 2020;383(10):919-930.  https://doi.org/10.1056/NEJMoa1916945
  15. Paganoni S, Hendrix S, Dickson SP, et al. Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis. Muscle Nerve. 2021;63(1):31-39.  https://doi.org/10.1002/mus.27091
  16. Paganoni S, Hendrix S, Dickson SP, et al. Effect of sodium phenylbutyrate/taurursodiol on tracheostomy/ventilation-free survival and hospitalisation in amyotrophic lateral sclerosis: long-term results from the CENTAUR trial. J Neurol Neurosurg Psychiatry. 2022;93(8):871-875.  https://doi.org/10.1136/jnnp-2022-329024
  17. Miller T, Cudkowicz M, Shaw PJ, et al. Phase 1-2 Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. N Engl J Med. 2020;383(2):109-119.  https://doi.org/10.1056/NEJMoa2003715
  18. Gibson LC, Hastings SF, McPhee I, et al. The inhibitory profile of Ibudilast against the human phosphodiesterase enzyme family. Eur J Pharmacol. 2006;538(1-3):39-42.  https://doi.org/10.1016/j.ejphar.2006.02.053
  19. Cho Y, Crichlow GV, Vermeire JJ, et al. Allosteric inhibition of macrophage migration inhibitory factor revealed by ibudilast. Proc Natl Acad Sci USA. 2010;107(25):11313-11318. https://doi.org/10.1073/pnas.1002716107
  20. Babu S, Hightower BG, Chan J, et al. Ibudilast (MN-166) in amyotrophic lateral sclerosis- an open label, safety and pharmacodynamic trial. Neuroimage Clin. 2021;30:102672. https://doi.org/10.1016/j.nicl.2021.102672
  21. Oskarsson B, Maragakis N, Bedlack RS, et al. MN-166 (ibudilast) in amyotrophic lateral sclerosis in a Phase IIb/III study: COMBAT-ALS study design. Neurodegener Dis Manag. 2021;11(6):431-443.  https://doi.org/10.2217/nmt-2021-0042
  22. Ketabforoush AHME, Chegini R, Barati S, et al. Masitinib: The promising actor in the next season of the Amyotrophic Lateral Sclerosis treatment series. Biomed Pharmacother. 2023;160:114378. https://doi.org/10.1016/j.biopha.2023.114378
  23. Mora JS, Bradley WG, Chaverri D, et al. Long-term survival analysis of masitinib in amyotrophic lateral sclerosis. Ther Adv Neurol Disord. 2021;14:17562864211030365. https://doi.org/10.1177/17562864211030365
  24. de Oliveira LMG, Carreira RB, de Oliveira JVR, et al. Impact of Plant-Derived Compounds on Amyotrophic Lateral Sclerosis. Neurotox Res. 2023;41(3):288-309.  https://doi.org/10.1007/s12640-022-00632-1
  25. Liao Y, He S, Liu D, et al. The efficacy and safety of Chinese herbal medicine as an add-on therapy for amyotrophic lateral sclerosis: An updated systematic review and meta-analysis of randomized controlled trials. Front Neurol. 2022;13:988034. https://doi.org/10.3389/fneur.2022.988034
  26. Song Y, Jia Q, Guan X, et al. Herbal medicine for amyotrophic lateral sclerosis: A systematic review and meta-analysis. Front Pharmacol. 2022;13:946548. https://doi.org/10.3389/fphar.2022.946548
  27. Kim S, Yang M, Ku B, et al. Efficacy of mecasin for treatment of amyotrophic lateral sclerosis: A phase IIa multicenter randomized double-blinded placebo-controlled trial. J Ethnopharmacol. 2023;315:116670. https://doi.org/10.1016/j.jep.2023.116670
  28. Li X, Tian Y, Wu H, et al. Network Pharmacology and Molecular Docking to Unveil the Mechanism of Shudihuang Against Amyotrophic Lateral Sclerosis. Curr Pharm Des. 2023 Jun 21.  https://doi.org/10.2174/1381612829666230621105552
  29. Zhu Q, Xu D, Huang H, et al. The safety and effectiveness of high-calorie therapy for treating amyotrophic lateral sclerosis: a systematic review and meta-analysis. J Neurol. 2023;270(10):4729-4743. https://doi.org/10.1007/s00415-023-11838-4
  30. Barros ANAB, Felipe MLDN, Barbosa IR, et al. Dietary Intake of Micronutrients and Disease Severity in Patients with Amyotrophic Lateral Sclerosis. Metabolites. 2023;13(6):696.  https://doi.org/10.3390/metabo13060696
  31. Wang T, Yang X, Du R, et al. Acupuncture in the Treatment of Amyotrophic Lateral Sclerosis: A Research Progress in Clinical Trials. Altern Ther Health Med. 2023 Aug 25:AT9112.
  32. Abrahao A, Meng Y, Llinas M, et al. First-in-human trial of blood-brain barrier opening in amyotrophic lateral sclerosis using MR-guided focused ultrasound. Nat Commun. 2019;10(1):4373. https://doi.org/10.1038/s41467-019-12426-9
  33. Ranieri F, Mariotto S, Dubbioso R, et al. Brain Stimulation as a Therapeutic Tool in Amyotrophic Lateral Sclerosis: Current Status and Interaction With Mechanisms of Altered Cortical Excitability. Front Neurol. 2021;11:605335. https://doi.org/10.3389/fneur.2020.605335
  34. Di Lazzaro V, Oliviero A, Saturno E, et al. Motor cortex stimulation for amyotrophic lateral sclerosis. Time for a therapeutic trial? Clin Neurophysiol. 2004;115(6):1479-1485. https://doi.org/10.1016/j.clinph.2004.01.027
  35. Di Lazzaro V, Pilato F, Profice P, et al. Motor cortex stimulation for ALS: a double blind placebo-controlled study. Neurosci Lett. 2009;464(1):18-21.  https://doi.org/10.1016/j.neulet.2009.08.020
  36. Di Lazzaro V, Dileone M, Pilato F, et al. Repetitive transcranial magnetic stimulation for ALS. A preliminary controlled study. Neurosci Lett. 2006;408(2):135-140.  https://doi.org/10.1016/j.neulet.2006.08.069
  37. Zanette G, Forgione A, Manganotti P, et al. The effect of repetitive transcranial magnetic stimulation on motor performance, fatigue and quality of life in amyotrophic lateral sclerosis. J Neurol Sci. 2008;270(1-2):18-22.  https://doi.org/10.1016/j.jns.2008.01.011
  38. Bjornevik K, Cortese M, Furtado JD, et al. Association of Polyunsaturated Fatty Acids and Clinical Progression in Patients With ALS: Post Hoc Analysis of the EMPOWER Trial. Neurology. 2023;10.1212/WNL.0000000000207485. https://doi.org/10.1212/WNL.0000000000207485
  39. Sassi S, Bianchi E, Diamanti L, et al. Retrospective observational study on the use of acetyl-L-carnitine in ALS. J Neurol. 2023;270(11):5344-5357. https://doi.org/10.1007/s00415-023-11844-6
  40. Oki R, Izumi Y, Fujita K, et al. Efficacy and Safety of Ultrahigh-Dose Methylcobalamin in Early-Stage Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial. JAMA Neurol. 2022;79(6):575-583.  https://doi.org/10.1001/jamaneurol.2022.0901
  41. Hu N, Wang X. The level of homocysteine in amyotrophic lateral sclerosis: a systematic review and meta-analysis. Neurol Sci. 2023;44(4):1185-1192. https://doi.org/10.1007/s10072-022-06518-6
  42. Mann RH. Impaired Thiamine Metabolism in Amyotrophic Lateral Sclerosis and Its Potential Treatment With Benfotiamine: A Case Report and a Review of the Literature. Cureus. 2023;15(6):e40511. https://doi.org/10.7759/cureus.40511
  43. Kutlubaev MA, Areprintseva DK, Pervushina EV. The influence of uric acid on the course of amyotrophic lateral sclerosis. S.S. Korsakov Journal of Neurology and Psychiatry. 2023;123(5):177-180. (In Russ.). https://doi.org/10.17116/jnevro2023123051177
  44. Walk D, Nicholson K, Locatelli E, et al. Randomized trial of inosine for urate elevation in amyotrophic lateral sclerosis. Muscle Nerve. 2023;67(5):378-386.  https://doi.org/10.1002/mus.27807
  45. Takahashi F, Kano O, Nagano Y, et al. Associations between urate levels and amyotrophic lateral sclerosis functional score with edaravone treatment: Post hoc analysis of studies MCI186-16, MCI186-17, and MCI186-19. Muscle Nerve. 2022;66(5):583-592.  https://doi.org/10.1002/mus.27699
  46. Najafi S, Najafi P, Kaffash Farkhad N, et al. Mesenchymal stem cell therapy in amyotrophic lateral sclerosis (ALS) patients: A comprehensive review of disease information and future perspectives. Iran J Basic Med Sci. 2023;26(8):872-881.  https://doi.org/10.22038/IJBMS.2023.66364.14572
  47. Suzuki M, McHugh J, Tork C, et al. Direct muscle delivery of GDNF with human mesenchymal stem cells improves motor neuron survival and function in a rat model of familial ALS. Mol Ther. 2008;16(12):2002-2010. https://doi.org/10.1038/mt.2008.197
  48. Uccelli A, Milanese M, Principato MC, et al. Intravenous mesenchymal stem cells improve survival and motor function in experimental amyotrophic lateral sclerosis. Mol Med. 2012;18:794-804. 
  49. Abdul Wahid SF, Law ZK, et al. Cell-based therapies for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev. 2019;12(12):CD011742. https://doi.org/10.1002/14651858.CD011742.pub3
  50. Papikinos T, Krokidis MG, Vrahatis A, et al. Signature-Based Computational Drug Repurposing for Amyotrophic Lateral Sclerosis. Adv Exp Med Biol. 2023;1424:201-211.  https://doi.org/10.1007/978-3-031-31982-2_22
  51. Bartus RT, Bétourné A, Basile A, et al. β2-Adrenoceptor agonists as novel, safe and potentially effective therapies for Amyotrophic lateral sclerosis (ALS). Neurobiol Dis. 2016;85:11-24.  https://doi.org/10.1016/j.nbd.2015.10.006
  52. Li X, Koeberl DD, Lutz MW, et al. Clenbuterol Treatment Is Safe and Associated With Slowed Disease Progression in a Small Open-Label Trial in Patients With Amyotrophic Lateral Sclerosis. J Clin Neuromuscul Dis. 2023;24(4):214-221.  https://doi.org/10.1097/CND.0000000000000438
  53. Cudkowicz M, Genge A, Maragakis N, et al. Safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis (the REFALS study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Neurol. 2021;20(10):821-831.  https://doi.org/10.1016/S1474-4422(21)00242-8
  54. Morimoto S, Takahashi S, Ito D, et al. Phase 1/2a clinical trial in ALS with ropinirole, a drug candidate identified by iPSC drug discovery. Cell Stem Cell. 2023;30(6):766-780.e9.  https://doi.org/10.1016/j.stem.2023.04.017
  55. Salomon-Zimri S, Pushett A, Russek-Blum N, et al. Combination of ciprofloxacin/celecoxib as a novel therapeutic strategy for ALS. Amyotroph Lateral Scler Frontotemporal Degener. 2023;24(3-4):263-271.  https://doi.org/10.1080/21678421.2022.2119868
  56. Willemse SW, Harley P, van Eijk RPA, et al. UNC13A in amyotrophic lateral sclerosis: from genetic association to therapeutic target. J Neurol Neurosurg Psychiatry. 2023;94(8):649-656.  https://doi.org/10.1136/jnnp-2022-330504
  57. Hong D, Zhang C, Wu W, et al. Modulation of the gut-brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis. Front Neurol. 2023;14:1133546. https://doi.org/10.3389/fneur.2023.1133546
  58. Benatar M, Wuu J, McHutchison C, et al. Preventing amyotrophic lateral sclerosis: insights from pre-symptomatic neurodegenerative diseases. Brain. 2022;145(1):27-44.  https://doi.org/10.1093/brain/awab404
  59. Khabibrakhmanov AN, Mukhamedyarov MA, Bogdanov EI. Biomarkers of amyotrophic lateral sclerosis. S.S. Korsakov Journal of Neurology and Psychiatry. 2022;122(5):30-35. (In Russ.). https://doi.org/10.17116/jnevro202212205130
  60. Li Hi Shing S, McKenna MC, Siah WF, et al. The imaging signature of C9orf72 hexanucleotide repeat expansions: implications for clinical trials and therapy development. Brain Imaging Behav. 2021;15(5):2693-2719. https://doi.org/10.1007/s11682-020-00429-w
  61. Bjornevik K, O’Reilly EJ, Molsberry S, et al. Prediagnostic Neurofilament Light Chain Levels in Amyotrophic Lateral Sclerosis. Neurology. 2021;97(15):e1466-1474. https://doi.org/10.1212/WNL.0000000000012632
  62. Mariosa D, Hammar N, Malmström H, et al. Blood biomarkers of carbohydrate, lipid, and apolipoprotein metabolisms and risk of amyotrophic lateral sclerosis: A more than 20-year follow-up of the Swedish AMORIS cohort. Ann Neurol. 2017;81(5):718-728.  https://doi.org/10.1002/ana.24936
  63. Thompson AG, Talbot K, Turner MR. Higher blood high density lipoprotein and apolipoprotein A1 levels are associated with reduced risk of developing amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2022;93(1):75-81.  https://doi.org/10.1136/jnnp-2021-327133
  64. Westeneng HJ, van Veenhuijzen K, van der Spek RA, et al. Associations between lifestyle and amyotrophic lateral sclerosis stratified by C9orf72 genotype: a longitudinal, population-based, case-control study. Lancet Neurol. 2021;20(5):373-384.  https://doi.org/10.1016/S1474-4422(21)00042-9
  65. Dorst J, Weydt P, Brenner D, et al. Metabolic alterations precede neurofilament changes in presymptomatic ALS gene carriers. EBioMedicine. 2023;90:104521. https://doi.org/10.1016/j.ebiom.2023.104521
  66. Kmetzsch V, Anquetil V, Saracino D, et al. Plasma microRNA signature in presymptomatic and symptomatic subjects with C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2021;92(5):485-493.  https://doi.org/10.1136/jnnp-2020-324647
  67. Irwin KE, Jasin P, Braunstein KE, et al. A fluid biomarker reveals loss of TDP-43 splicing repression in presymptomatic ALS. bioRxiv 2023. Preprint. https://doi.org/10.1101/2023.01.23.525202
  68. Benatar M, Wuu J, Andersen PM, et al. Design of a Randomized, Placebo-Controlled, Phase 3 Trial of Tofersen Initiated in Clinically Presymptomatic SOD1 Variant Carriers: the ATLAS Study. Neurotherapeutics. 2022;19(4):1248-1258. https://doi.org/10.1007/s13311-022-01237-4
  69. Tzeplaeff L, Wilfling S, Requardt MV, et al. Current State and Future Directions in the Therapy of ALS. Cells. 2023;12(11):1523. https://doi.org/10.3390/cells12111523
  70. Bireley JD, Morren JA. CNM-Au8: an experimental agent for the treatment of amyotrophic lateral sclerosis (ALS). Expert Opin Investig Drugs. 2023;1-7.  https://doi.org/10.1080/13543784.2023.2252738
  71. Amado DA, Davidson BL. Gene therapy for ALS: A review. Mol Ther. 2021;29(12):3345-3358. https://doi.org/10.1016/j.ymthe.2021.04.008
  72. Chambers C, Lichten L, Crook A, et al. Incorporating Genetic Testing Into the Care of Patients With Amyotrophic Lateral Sclerosis/Frontotemporal Degeneration Spectrum Disorders. Neurol Clin Pract. 2023;13(5):e200201. https://doi.org/10.1212/CPJ.0000000000200201
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