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Mesenchymal stem cells as new perspective for the treatment of alcohol use disorder

Gene Therapy volume 27, pages 471–473 (2020)Cite this article

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The harmful use of alcohol causes around 5% of the global burden of disease, according to the World Health Organization [1]. Despite this, few medications have been approved for the treatment of alcohol use disorders (AUD). Preclinical researches have accumulated knowledge to understand the neurobiological mechanisms behind the disease, but with few success to translate into new pharmacological treatments.

To date, few medications—disulfiram, naltrexone, acamprosate, and nalmefene (the last one approved only in Europe)—are licensed to AUD and scientists continue searching for new effective treatments, mostly because of the current state of the drugs available to treat AUD. The efficacy and mechanism of action of acamprosate, also designed as the calcium salt of N-acetyl-homotaurine, are still under scrutiny. Indeed, a paper by Spanagel et al. [2] proposed that the activity moiety attributed to acamprosate is related to the Ca+2 rather than its actions on glycine or glutamate systems. Naltrexone, an opioid antagonist, has been used as anticraving medication for AUD yet its efficacy and security in long-term treatments are limited. Moreover, the response heterogeneity to naltrexone treatment seems to rely on genetic factors [3]. Nalmefene differs from naltrexone for its partial agonist activity at kappa receptors [4] and is more effective in reducing alcohol intake than in maintaining abstinence [5].

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Fig. 1: Ethanol produces reactive oxygen species (ROS) during its metabolism, activates Toll-like receptors (TLR4)/NF-κB signaling, and pro-inflammatory cytokines.

References

  1. World Health Organization. Global status report on alcohol and health. Geneva: World Health Organization; 2018.

  2. Spanagel R, Vengeliene V, Jandeleit B, Fischer WN, Grindstaff K, Zhang X, et al. Acamprosate produces its anti-relapse effects via calcium. Neuropsychopharmacology. 2014;39:783–91.

    Article  CAS  Google Scholar 

  3. Barr CS, Chen SA, Schwandt ML, Lindell SG, Sun H, Suomi SJ, et al. Suppression of alcohol preference by naltrexone in the rhesus macaque: a critical role of genetic variation at the micro-opioid receptor gene locus. Biol Psychiatry. 2010;67:78–80.

    Article  CAS  Google Scholar 

  4. Bart G, Schluger JH, Borg L, Ho A, Bidlack JM, Kreek MJ. Nalmefene induced elevation in serum prolactin in normal human volunteers: partial kappa opioid agonist activity? Neuropsychopharmacology. 2005;30:2254–62.

    Article  CAS  Google Scholar 

  5. Jonas A, Amick HR, Feltner C, Bobashev G, Thomas K, Wines R, et al. Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis. JAMA. 2014;311:1889–900.

    Article  Google Scholar 

  6. Font L, Aragon CM, Miquel M. Ethanol-induced conditioned place preference, but not aversion, is blocked by treatment with D-penicillamine, an inactivation agent for acetaldehyde. Psychopharmacology. 2006;184:56–64.

    Article  CAS  Google Scholar 

  7. Quertemont E, Tambour S, Tirelli E. The role of acetaldehyde in the neurobehavioral effects of ethanol: a comprehensive review of animal studies. Prog Neurobiol. 2005;75:247–74.

    Article  CAS  Google Scholar 

  8. Peana AT, Porcheddu V, Bennardini F, Carta A, Rosas M, Acquas E. Role of ethanol-derived acetaldehyde in operant oral self-administration of ethanol in rats. Psychopharmacology. 2015;232:4269–76.

    Article  CAS  Google Scholar 

  9. Karahanian E, Quintanilla ME, Tampier L, Rivera-Meza M, Bustamante D, Gonzalez-Lira V, et al. Ethanol as a prodrug: brain metabolism of ethanol mediates its reinforcing effects. Alcohol Clin Exp Res. 2011;35:606–12.

    Article  CAS  Google Scholar 

  10. Quintanilla ME, Tampier L, Karahanian E, Rivera-Meza M, Herrera-Marschitz M, Israel Y. Reward and relapse: complete gene-induced dissociation in an animal model of alcohol dependence. Alcohol Clin Exp Res. 2012;36:517–22.

    Article  CAS  Google Scholar 

  11. Israel Y, Quintanilla E, Ezquer F, Morales P, Rivera-Meza M, Karahanian E, et al. Gene and cell therapy on the acquisition and relapse-like binge drinking in a model of alcoholism: translational options. Gene Ther. 2019;26:407–17.

    Article  Google Scholar 

  12. Ocaranza P, Quintanilla ME, Tampier L, Karahanian E, Sapag A, Israel Y. Gene therapy reduces ethanol intake in an animal model of alcohol dependence. Alcohol Clin Exp Res. 2008;32:52–7.

    Article  CAS  Google Scholar 

  13. Fliegel S, Brand I, Spanagel R, Noori HR. Ethanol-induced alterations of amino acids measured by in vivo microdialysis in rats: a meta-analysis. In Silico Pharmacol. 2013;1:7.

    Article  Google Scholar 

  14. Gass JT, Sinclair CM, Cleva RM, Widholm JJ, Olive MF. Alcohol-seeking behavior is associated with increased glutamate transmission in basolateral amygdala and nucleus accumbens as measured by glutamate-oxidase-coated biosensors. Addict Biol. 2011;16:215–28.

    Article  CAS  Google Scholar 

  15. Trotti D, Danbolt NC, Volterra A. Glutamate transporters are oxidant-vulnerable: a molecular link between oxidative and excitotoxic neurodegeneration? Trends Pharmacol Sci. 1998;19:328–34.

    Article  CAS  Google Scholar 

  16. Haroon E, Miller AH, Sanacora G. Inflammation, glutamate and glia: a trio of trouble in mood disorders. Neuropsychopharmacology. 2017;42:193–215.

    Article  CAS  Google Scholar 

  17. Guerri C, Pascual M. Impact of neuroimmune activation induced by alcohol or drug abuse on adolescente brain development. Int J Dev Neurosci. 2019;77:89–98.

    Article  CAS  Google Scholar 

  18. Karlsson C, Schank JR, Rehman F, Stojakovic A, Björk K, Barbier E, et al. Proinflammatory signaling regulates voluntary alcohol intake and stress-induced consumption after exposure to social defeat stress in mice. Addict Biol. 2017;22:1279–88.

    Article  CAS  Google Scholar 

  19. Caplan AI. Mesenchymal stem cells. J Ortoph Res. 1991;9:641–50.

    Article  CAS  Google Scholar 

  20. Caplan AI. Mesenchymal stem cells: time to change the name! Stem Cells Transl Med. 2017;66:1445–51.

    Article  Google Scholar 

  21. Zhang Y, Chopp M, Liu XS, Katakowski M, Wang X. Exosomes derived from mesenchymal stromal cells promote axonal growth of cortical neurons. Mol Neurobiol. 2016;54:2659–73.

    Article  Google Scholar 

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  1. Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av Prof. Lineu Prestes, 1524, São Paulo, SP, 05508-900, Brazil

    Rosana Camarini

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Correspondence to Rosana Camarini.

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Camarini, R. Mesenchymal stem cells as new perspective for the treatment of alcohol use disorder. Gene Ther 27, 471–473 (2020). https://doi.org/10.1038/s41434-020-0133-0

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