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Current Aging Science

Author(s): Hossein Pakdaman, Ali Amini Harandi*, Koroush Gharagozli, Fatemeh Siavoshi, Siavash Shirzadeh Barough, Ehsan Sharifipour, Akram Esfandani, Saba Ilkhani, Fatemeh Sadat Tabatabaei and Seyed Ali Sobhanian

DOI: 10.2174/1874609816666230224111759

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A Long-term Study of NeuroAid (MLC601, MLC901) in Patients with Alzheimer's Disease; An Extension 8-year Follow-up Study

Page: [234 - 239] Pages: 6

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Abstract

Background: MLC601 and MLC901 showed neuroprotective and neuroregenerative properties and positive results in the treatment of dementia and cognitive impairment. This study aimed to investigate the long-term benefits of monotherapy with MLC601 and MLC901 in patients with Alzheimer's disease (AD).

Methods: In this study, patients with AD, diagnosed by DSM-IV criteria, were enrolled. Patients have received MLC601 for four years, and their regimen has changed to MLC901 for another four years. Recruited patients were followed to assess the efficacy and safety first of MLC601 and MLC901. Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog) were used to assess cognitive function. Safety was evaluated by monitoring adverse events (AEs) and abnormal findings in physical examinations or lab tests.

Results: At the end of the trial, the changes in the mean (±SD) MMSE and ADAS-Cog scores were 5.1 (3.09) and 12.5 (10.89), respectively. Both scores showed a significant change in repeated measure analysis, with the ADAS-Cog score indicating a higher change than the MMSE score (P < 0.001).

Conclusion: For more than eight years, we studied monotherapy with NeuroAid (MLC601, MLC901) in patients with AD. The study contributes further to the long-term safety and efficacy data of MLC in patients with AD.

Graphical Abstract

[1]
Qiu C, Kivipelto M, Von Strauss E. Epidemiology of Alzheimer’s disease: Occurrence, determinants, and strategies toward intervention. Dialogues Clin Neurosci 2009; 11(2): 111-28.
[http://dx.doi.org/10.31887/DCNS.2009.11.2/cqiu] [PMID: 19585947]
[2]
Wimo A, Guerchet M, Ali GC, et al. The worldwide costs of dementia 2015 and comparisons with 2010. Alzheimers Dement 2017; 13(1): 1-7.
[http://dx.doi.org/10.1016/j.jalz.2016.07.150] [PMID: 27583652]
[3]
World Health Organization (WHO)Global action plan on the public health response to dementia 2017-2025. 2017. Available from : https://www.who.int/publications/i/item/global-action-plan-on-the-public-health-response-to-dementia-2017---2025
[4]
World Health Organization (WHO) World population prospects: The 2019 revision. 2019. Available from : [https://population.un.org/wpp/publications/files/wpp2019_highlights.pdf
[5]
Knopman DS, Jones DT, Greicius MD. Failure to demonstrate efficacy of aducanumab: An analysis of the EMERGE and ENGAGE trials as reported by Biogen, December 2019. Alzheimers Dement 2021; 17(4): 696-701.
[http://dx.doi.org/10.1002/alz.12213] [PMID: 33135381]
[6]
Justin M, David M. Alzheimer’s disease: An update on pathobiology and treatment strategies. Cell 2019; 179(2): 312-39.
[http://dx.doi.org/10.1016/j.cell.2019.09.001] [PMID: 31564456]
[7]
Heurteaux C, Gandin C, Borsotto M, et al. Neuroprotective and neuroproliferative activities of NeuroAid (MLC601, MLC901), a Chinese medicine, in vitro and in vivo. Neuropharmacology 2010; 58(7): 987-1001.
[http://dx.doi.org/10.1016/j.neuropharm.2010.01.001] [PMID: 20064536]
[8]
Heurteaux C, Widmann C. Moha ou Maati H, et al. NeuroAiD Properties for neuroprotection and neurorepair. Cerebrovasc Dis 2013; 35S1: 1-7.
[http://dx.doi.org/10.1159/000346228] [PMID: 23548913]
[9]
Tsai MC, Chang CP, Peng SW, et al. Therapeutic efficacy of Neuro AiD™ (MLC 601), a traditional Chinese medicine, in experimental traumatic brain injury. J Neuroimmune Pharmacol 2015; 10(1): 45-54.
[http://dx.doi.org/10.1007/s11481-014-9570-0] [PMID: 25331680]
[10]
Moha Ou Maati H, Borsotto M, Chatelain F, Widmann C, Lazdunski M, Heurteaux C. Activation of ATP-sensitive potassium channels as an element of the neuroprotective effects of the traditional Chinese medicine MLC901 against oxygen glucose deprivation. Neuropharmacology 2012; 63(4): 692-700.
[http://dx.doi.org/10.1016/j.neuropharm.2012.05.035] [PMID: 22659084]
[11]
Quintard H, Lorivel T, Gandin C, Lazdunski M, Heurteaux C. MLC901, a traditional Chinese medicine induces neuroprotective and neuroregenerative benefits after traumatic brain injury in rats. Neuroscience 2014; 277: 72-86.
[http://dx.doi.org/10.1016/j.neuroscience.2014.06.047] [PMID: 24993477]
[12]
Theadom A, Barker-Collo S, Jones KM, Parmar P, Bhattacharjee R, Feigin VL. MLC 901 (NeuroAiD II ™) for cognition after traumatic brain injury: A pilot randomized clinical trial. Eur J Neurol 2018; 25(8): 1055-e82.
[http://dx.doi.org/10.1111/ene.13653] [PMID: 29611892]
[13]
Chen CLH, Ikram K, Anqi Q, Yin WT, Chen A, Venketasubramanian N. The NeuroAiD II (MLC901) in vascular cognitive impairment study (NEURITES). Cerebrovasc Dis 2013; 35(S1): 23-9.
[http://dx.doi.org/10.1159/000346234] [PMID: 23548916]
[14]
Ranuh IAR, Sari GM, Utomo B, Suroto NS, Fauzi AA. Systematic review and meta-analysis of the efficacy of MLC901 (NeuroAiD IITM) for acute ischemic brain injury in animal models. J Evid Based Integr Med. 2021.26: 2515690X211039219..
[http://dx.doi.org/10.1177/2515690X211039219]
[15]
Lee WT, Hsian CCL, Lim YA. The effects of MLC901 on tau phosphorylation. Neuroreport 2017; 28(16): 1043-8.
[http://dx.doi.org/10.1097/WNR.0000000000000884] [PMID: 28902708]
[16]
Widmann C, Gandin C, Petit-Paitel A, Lazdunski M, Heurteaux C. The traditional Chinese medicine MLC901 inhibits inflammation processes after focal cerebral ischemia. Sci Rep 2018; 8(1): 18062.
[http://dx.doi.org/10.1038/s41598-018-36138-0] [PMID: 30584250]
[17]
Lorivel T, Gandin C, Veyssière J, Lazdunski M, Heurteaux C. Positive effects of the traditional Chinese medicine MLC 901 in cognitive tasks. J Neurosci Res 2015; 93(11): 1648-63.
[http://dx.doi.org/10.1002/jnr.23591] [PMID: 25821139]
[18]
Venketasubramanian N, Young SH, Tay SS, et al. Chinese medicine NeuroAiD efficacy on stroke recovery-extension study (CHIMES-E): A multicenter study of long-term efficacy. Cerebrovasc Dis 2015; 39(5-6): 309-18.
[http://dx.doi.org/10.1159/000382082] [PMID: 25925713]
[19]
Harandi A, Ashrafi F, Tabatabaei M, Ghorbani A, Hatamian H, Pakdaman H, et al. Efficacy and tolerability of MLC601 in patients with mild to moderate Alzheimer disease who were unable to tolerate or failed to benefit from treatment with rivastigmine. Br J Med Med Res 2013; 3(2): 341-50.
[http://dx.doi.org/10.9734/BJMMR/2013/2537]
[20]
Pakdaman H, Harandi AA, Hatamian H, et al. Effectiveness and safety of MLC601 in the treatment of mild to moderate Alzheimer’s disease: A multicenter, randomized controlled trial. Dement Geriatr Cogn Disord Extra 2015; 5(1): 96-106.
[http://dx.doi.org/10.1159/000375295] [PMID: 25873931]
[21]
Pakdaman H, Gharagozli K, Abbasi M, et al. Efficacy and safety of MLC601 in patients with mild to moderate Alzheimer disease: An extension 4-year follow-up study. Dement Geriatr Cogn Disord Extra 2018; 8(1): 174-9.
[http://dx.doi.org/10.1159/000488482] [PMID: 29805383]
[22]
Lim YA, Murray LA, Lai MKP, Chen C. NeuroAiD® (MLC601) and amyloid precursor protein processing. Cerebrovasc Dis 2013; 35(S1): 30-7.
[http://dx.doi.org/10.1159/000346236] [PMID: 23548917]
[23]
Pakdaman H, Amini Harandi A, Abbasi M, et al. Efficacy and safety of MLC601 in the treatment of mild cognitive impairment: A pilot, randomized, double-blind, placebo-controlled study. Dement Geriatr Cogn Disord Extra 2017; 7(1): 136-42.
[http://dx.doi.org/10.1159/000458521] [PMID: 28626468]
[24]
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. fourth Edition (DSMIV). American Psychiatric Press: Washington, 1994; pp. 147-54.
[25]
Folstein MF, Folstein SE, McHugh PR. Mini-mental state. J Psychiatr Res 1975; 12(3): 189-98.
[http://dx.doi.org/10.1016/0022-3956(75)90026-6] [PMID: 1202204]
[26]
Weyer G, Erzigkeit H, Kanowski S, Ihl R, Hadler D. Alzheimer’s disease assessment scale: Reliability and validity in a multicenter clinical trial. Int Psychogeriatr 1997; 9(2): 123-38.
[http://dx.doi.org/10.1017/S1041610297004298] [PMID: 9309486]
[27]
Chen CLH, Sharma PR, Tan BY, Low C, Venketasubramanian N. The Alzheimer’s disease therapy with neuroaid (ATHENE) study protocol: Assessing the safety and efficacy of neuroaid II (MLC901) in patients with mild-to-moderate Alzheimer’s disease stable on cholinesterase inhibitors or memantine—A randomized, double-blind, placebo-controlled trial. Alzheimers Dement 2019; 5(1): 38-45.
[http://dx.doi.org/10.1016/j.trci.2018.12.001] [PMID: 30723778]
[28]
Chen CL, Lu Q, Moorakonda RB, et al. Alzheimer’s disease therapy with neuroaid (athene): A randomized double-blind delayed-start trial. J Am Med Dir Assoc 2022; 23(3): 379-86.e3.
[http://dx.doi.org/10.1016/j.jamda.2021.10.018] [PMID: 34856171]
[29]
Zhang C, Tao W, Zhang J, Liu M, Li J. Neuroaid for improving recovery after ischemic stroke. Cochrane Libr 2017; 2017(8): CD009757.
[http://dx.doi.org/10.1002/14651858.CD009757.pub3]
[30]
Farlow MR, Lilly ML. Rivastigmine: An open-label, observational study of safety and effectiveness in treating patients with Alzheimer’s disease for up to 5 years. BMC Geriatr 2005; 5(1): 3.
[http://dx.doi.org/10.1186/1471-2318-5-3] [PMID: 15659242]
[31]
Rogers SL, Friedhoff LT. Long-term efficacy and safety of donepezil in the treatment of Alzheimer’s disease: An interim analysis of the results of a US multicentre open label extension study. Eur Neuropsychopharmacol 1998; 8(1): 67-75.
[http://dx.doi.org/10.1016/S0924-977X(97)00079-5] [PMID: 9452942]
[32]
Doody RS, Geldmacher DS, Gordon B, Perdomo CA, Pratt RD, Group DS. Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer disease. Arch Neurol 2001; 58(3): 427-33.
[http://dx.doi.org/10.1001/archneur.58.3.427] [PMID: 11255446]
[33]
Lanctôt KL, Herrmann N, Yau KK, et al. Efficacy and safety of cholinesterase inhibitors in Alzheimer’s disease: A meta-analysis. CMAJ 2003; 169(6): 557-64.
[PMID: 12975222]