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Neuroprotection in Huntington Disease

  • Kewal K. Jain
Protocol
  • 274 Downloads
Part of the Springer Protocols Handbooks book series (SPH)

Abstract

Huntington’s disease (HD) is an autosomal dominant hereditary disorder characterized by chorea (excessive, spontaneous, irregularly timed abrupt movements), disturbed voluntary motor performance, behavioral changes and dementia. Functional capacity slowly declines as a result of increasing motor and cognitive deficits until the patient becomes bedridden. The course is progressive, with death usually occurring 15–20 years after disease onset. Death is most frequently caused by aspiration pneumonia.

References

  1. An MC, Zhang N, Scott G, et al. Genetic Correction of Huntington’s Disease Phenotypes in Induced Pluripotent Stem Cells. Cell Stem Cell 2012;11:253–63.CrossRefGoogle Scholar
  2. Appl T, Kaltenbach L, Lo DC, Terstappen GC. Targeting mutant huntingtin for the development of disease-modifying therapy. Drug Discov Today 2012;17:1217–23.CrossRefGoogle Scholar
  3. Aronin N, Moore M. Hunting Down Huntingtin. N Engl J Med 2012;367:1753–54.CrossRefGoogle Scholar
  4. Bachoud-Levi A, Gaura V, Brugieres P, et al. Effect of fetal neural transplants in patients with Huntington’s disease 6 years after surgery: a long-term follow-up study. Lancet Neurol 2006;5:303–9.CrossRefGoogle Scholar
  5. Benraiss A, Toner MJ, Xu Q, et al. Sustained Mobilization of Endogenous Neural Progenitors Delays Disease Progression in a Transgenic Model of Huntington’s Disease. Cell Stem Cell 2013;12:787–99.CrossRefGoogle Scholar
  6. Cardinale A, Fusco FR. Inhibition of phosphodiesterases as a strategy to achieve neuroprotection in Huntington’s disease. CNS Neurosci Ther 2018;24(4):319–328.CrossRefGoogle Scholar
  7. Chopra V, Fox JH, Lieberman G, et al. A small-molecule therapeutic lead for Huntington’s disease: Preclinical pharmacology and efficacy of C2-8 in the R6/2 transgenic mouse. PNAS 2007;104:16685–9.CrossRefGoogle Scholar
  8. Connor B, Sun Y, von Hieber D, et al. AAV1/2-mediated BDNF gene therapy in a transgenic rat model of Huntington’s disease. Gene Ther 2016;23:283–95.CrossRefGoogle Scholar
  9. de Yebenes JG, Landwehrmeyer B, Squitieri F, et al; MermaiHD study investigators. Pridopidine for the treatment of motor function in patients with Huntington’s disease (MermaiHD): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Neurol 2011;10:1049–57.CrossRefGoogle Scholar
  10. Di Pardo A, Amico E, Favellato M, et al. FTY720 (fingolimod) is a neuroprotective and disease-modifying agent in cellular and mouse models of Huntington disease. Mol Genet 2014;23:2251–2265.Google Scholar
  11. Evers MM, Pepers BA, van Deutekom JC, et al. Targeting several CAG expansion diseases by a single antisense oligonucleotide. PLoS One 2011;6(9):e24308.CrossRefGoogle Scholar
  12. Ferreira JJ, Rosser A, Craufurd D, et al. Ethyl-eicosapentaenoic acid treatment in Huntington’s disease: A placebo-controlled clinical trial. Mov Disord 2015;30:1426–9.CrossRefGoogle Scholar
  13. Gibrat C, Cicchetti F. Potential of cystamine and cysteamine in the treatment of neurodegenerative diseases. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:380–9.CrossRefGoogle Scholar
  14. Golas MM, Sander B. Use of human stem cells in Huntington disease modeling and translational research. Exp Neurol 2016;278:76–90.CrossRefGoogle Scholar
  15. Huntington Study Group HART Investigators. A randomized, double-blind, placebo-controlled trial of pridopidine in Huntington’s disease. Mov Disord 2013;28:1407–15.CrossRefGoogle Scholar
  16. Jain KK. Fingolimod. In, Roos RP (ed) MedLink Neurology. Medlink Publishing Corporation, San Diego, California, 2019.Google Scholar
  17. Jain KK. Pramipexole. In, Roos RP (ed) MedLink Neurology. Medlink Publishing Corporation, San Diego, California, 2019a.Google Scholar
  18. Jeong H, Cohen DE, Cui L, et al. Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway. Nat Med 2011;18:159–65.CrossRefGoogle Scholar
  19. Jiang M, Wang J, Fu J, et al. Neuroprotective role of Sirt1 in mammalian models of Huntington’s disease through activation of multiple Sirt1 targets. Nat Med 2011;18:153–8.CrossRefGoogle Scholar
  20. Lee J, Hwang YJ, Kim KY, et al. Epigenetic Mechanisms of Neurodegeneration in Huntington’s Disease. Neurotherapeutics 2013;10:664–76.CrossRefGoogle Scholar
  21. Luis-Ravelo D, Estévez-Silva H, Barroso-Chinea P, et al. Pramipexole reduces soluble mutant huntingtin and protects striatal neurons through dopamine D3 receptors in a genetic model of Huntington’s disease. Exp Neurol 2019;299(Pt A):137–147.Google Scholar
  22. Luthi-Carter R, Taylor DM, Pallos J, et al. SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. PNAS 2010;107:7927–32.CrossRefGoogle Scholar
  23. Miguez A, García Díaz-Barriga G, Brito V, et al. Fingolimod (FTY720) enhances hippocampal synaptic plasticity and memory in Huntington’s disease by preventing p75NTR up-regulation and astrocyte-mediated inflammation. Mol Genet 2015;24:4948–57.Google Scholar
  24. Miller JP, Yates BE, Al-Ramahi I, et al. A Genome-Scale RNA interference screen identifies RRAS signaling as a pathologic feature of Huntington’s disease. PLoS Genet 2012;8:e1003042.CrossRefGoogle Scholar
  25. Monteys AM, Ebanks SA, Keiser MS, Davidson BL. CRISPR/Cas9 Editing of the Mutant Huntingtin Allele In Vitro and In Vivo. Mol Ther 2017;25:12–23.CrossRefGoogle Scholar
  26. Okamoto S, Pouladi MA, Talantova M, et al. Balance between synaptic versus extrasynaptic NMDA receptor activity influences inclusions and neurotoxicity of mutant huntingtin. Nat Med 2009;15:1407–13.CrossRefGoogle Scholar
  27. Patassini S, Giampà C, Martorana A, et al. Effects of simvastatin on neuroprotection and modulation of Bcl-2 and BAX in the rat quinolinic acid model of Huntington’s disease. Neurosci Lett 2008;448:166–9.CrossRefGoogle Scholar
  28. Prundean A, Youssov K, Humbert S, et al. A phase II, open-label evaluation of cysteamine tolerability in patients with Huntington’s disease. Mov Disord 2015;30:288–9.CrossRefGoogle Scholar
  29. Sbodio JI, Snyder SH, Paul BD. Golgi stress response reprograms cysteine metabolism to confer cytoprotection in Huntington’s disease. Proc Natl Acad Sci U S A 2018;115:780–5.CrossRefGoogle Scholar
  30. Sbodio JI, Snyder SH, Paul BD. Transcriptional control of amino acid homeostasis is disrupted in Huntington’s disease. Proc Natl Acad Sci U S A 2016;113:8843–8.CrossRefGoogle Scholar
  31. Shannon KM, Fraint A. Therapeutic advances in Huntington’s disease. Mov Disord 2015:30:1539–46.CrossRefGoogle Scholar
  32. Tang TS, Chen X, Liu J, Bezprozvanny I. Dopaminergic Signaling and Striatal Neurodegeneration in Huntington’s Disease. J Neurosci;2007;27:7899–7910.CrossRefGoogle Scholar
  33. Thomas EA, Coppola G, Desplats PA, et al. The HDAC inhibitor 4b ameliorates the disease phenotype and transcriptional abnormalities in Huntington’s disease transgenic mice. PNAS 2008;105:15564–9.CrossRefGoogle Scholar
  34. Vang S, Longley K, Steer CJ, Low WC. The Unexpected Uses of Urso- and Tauroursodeoxycholic Acid in the Treatment of Non-liver Diseases. Glob Adv Health Med 2014;3:58–69.CrossRefGoogle Scholar
  35. Verny C, Bachoud-Lévi AC, Durr A, et al. A randomized, double-blind, placebo-controlled trial evaluating cysteamine in Huntington’s disease. Mov Disord 2017;32:932–936.CrossRefGoogle Scholar
  36. Wild EJ, Tabrizi SJ. Therapies targeting DNA and RNA in Huntington’s disease. Lancet Neurol 2017;16:837–847.CrossRefGoogle Scholar
  37. Xiao G, Fan Q, Wang X, Zhou B. Huntington disease arises from a combinatory toxicity of polyglutamine and copper binding. Proc Natl Acad Sci U S A 2013;110:14995–5000.CrossRefGoogle Scholar
  38. Yu D, Pendergraff H, Liu J, et al. Single-stranded RNAs use RNAi to potently and allele-selectively inhibit mutant huntingtin expression. Cell 2012;150:895–908.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Kewal K. Jain
    • 1
  1. 1.Jain PharmaBiotechBaselSwitzerland

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