Advertisement

HDAC Inhibitors in Combinatorial Therapy for Treating Neurological Disorders

  • Shabir Ahmad Ganai
Chapter

Abstract

Histone deacetylase inhibitors (HDACi) when used singly (monotherapy) show limited therapeutic efficacy. This limited efficacy may be attributed to different resistance mechanisms generated by offending cells in response to these inhibitors. Moreover in monotherapy, the therapeutic effect is achieved at higher doses of HDACi at which even normal cells get sensitized. Thus this chapter deals with combinatorial therapeutic strategy involving HDACi in conjunction with other drugs. The combinatorial therapy imparts least toxicity to normal cells but shows additive or synergistic therapeutic effect against abnormal cells.

References

  1. Agrawal N, Pallos J, Slepko N, Apostol BL, Bodai L, Chang LW, Chiang AS, Thompson LM, Marsh JL (2005) Identification of combinatorial drug regimens for treatment of Huntington’s disease using Drosophila. Proc Natl Acad Sci U S A 102(10):3777–3781PubMedPubMedCentralCrossRefGoogle Scholar
  2. Auluck PK, Bonini NM (2002) Pharmacological prevention of Parkinson disease in Drosophila. Nat Med 8(11):1185–1186PubMedCrossRefGoogle Scholar
  3. Avila AM, Burnett BG, Taye AA, Gabanella F, Knight MA, Hartenstein P, Cizman Z, Di Prospero NA, Pellizzoni L, Fischbeck KH, Sumner CJ (2007) Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy. J Clin Invest 117(3):659–671PubMedPubMedCentralCrossRefGoogle Scholar
  4. Barker-Haliski M, Sills GJ, White HS (2014) What are the arguments for and against rational therapy for epilepsy? Adv Exp Med Biol 813:295–308PubMedCrossRefGoogle Scholar
  5. Brodie MJ, Yuen AW (1997) Lamotrigine substitution study: evidence for synergism with sodium valproate? 105 Study Group. Epilepsy Res 26(3):423–432PubMedCrossRefGoogle Scholar
  6. Chang JG, Hsieh-Li HM, Jong YJ, Wang NM, Tsai CH, Li H (2001) Treatment of spinal muscular atrophy by sodium butyrate. Proc Natl Acad Sci U S A 98(17):9808–9813PubMedPubMedCentralCrossRefGoogle Scholar
  7. Chen L-F, Greene WC (2004) Shaping the nuclear action of NF-κB. Nat Rev Mol Cell Biol 5:392PubMedCrossRefGoogle Scholar
  8. Cherian A, Thomas SV (2009) Status epilepticus. Ann Indian Acad Neurol 12(3):140–153PubMedPubMedCentralCrossRefGoogle Scholar
  9. Colombo E, Franceschetti S, Avanzini G, Mantegazza M (2013) Phenytoin inhibits the persistent sodium current in neocortical neurons by modifying its inactivation properties. PLoS One 8(1):29CrossRefGoogle Scholar
  10. Cuadrado-Tejedor M, Garcia-Barroso C, Sanzhez-Arias J, Mederos S, Rabal O, Ugarte A, Franco R, Pascual-Lucas M, Segura V, Perea G, Oyarzabal J, Garcia-Osta A (2015) Concomitant histone deacetylase and phosphodiesterase 5 inhibition synergistically prevents the disruption in synaptic plasticity and it reverses cognitive impairment in a mouse model of Alzheimer’s disease. Clin Epigenetics 7(108):015–0142Google Scholar
  11. Cuadrado-Tejedor M, Garcia-Barroso C, Sanchez-Arias JA, Rabal O, Perez-Gonzalez M, Mederos S, Ugarte A, Franco R, Segura V, Perea G, Oyarzabal J, Garcia-Osta A (2017) A first-in-class small-molecule that acts as a dual inhibitor of HDAC and PDE5 and that rescues hippocampal synaptic impairment in Alzheimer’s disease mice. Neuropsychopharmacology 42(2):524–539PubMedCrossRefGoogle Scholar
  12. Del Signore SJ, Amante DJ, Kim J, Stack EC, Goodrich S, Cormier K, Smith K, Cudkowicz ME, Ferrante RJ (2009) Combined riluzole and sodium phenylbutyrate therapy in transgenic amyotrophic lateral sclerosis mice. Amyotroph Lateral Scler 10(2):85–94PubMedCrossRefGoogle Scholar
  13. Doble A (1996) The pharmacology and mechanism of action of riluzole. Neurology 47(6 Suppl 4):S233–S241PubMedCrossRefGoogle Scholar
  14. Duranay R, Bashirov R, Şeytanoğlu A (2017) Simulation-based identification of optimal combination of drug candidates for spinal muscular atrophy. Procedia Comp Sci 120:253–259CrossRefGoogle Scholar
  15. Duvic M, Vu J (2007) Vorinostat: a new oral histone deacetylase inhibitor approved for cutaneous T-cell lymphoma. Expert Opin Investig Drugs 16(7):1111–1120PubMedCrossRefGoogle Scholar
  16. Eadie MJ (2012) Shortcomings in the current treatment of epilepsy. Expert Rev Neurother 12(12):1419–1427PubMedCrossRefGoogle Scholar
  17. Englund M, Hyllienmark L, Brismar T (2011) Effect of valproate, lamotrigine and levetiracetam on excitability and firing properties of CA1 neurons in rat brain slices. Cell Mol Neurobiol 31(4):645–652PubMedCrossRefGoogle Scholar
  18. Feng HL, Leng Y, Ma CH, Zhang J, Ren M, Chuang DM (2008) Combined lithium and valproate treatment delays disease onset, reduces neurological deficits and prolongs survival in an amyotrophic lateral sclerosis mouse model. Neuroscience 155(3):567–572PubMedPubMedCentralCrossRefGoogle Scholar
  19. Ganai SA (2014) HDAC INHIBITORS Entinostat and Suberoylanilide Hydroxamic Acid (SAHA): the ray of hope for cancer therapy. In: Wells RD, Bond JS, Klinman J, Masters BSS, Bell E (eds) Molecular life sciences: an Encyclopedic reference. Springer New York, New York, pp 1–16Google Scholar
  20. Ganai SA (2016a) Histone deacetylase inhibitor givinostat: the small-molecule with promising activity against therapeutically challenging haematological malignancies. J Chemother 28(4):247–254PubMedCrossRefGoogle Scholar
  21. Ganai SA (2016b) Panobinostat: the small molecule metalloenzyme inhibitor with Marvelous anticancer activity. Curr Top Med Chem 16(4):427–434PubMedCrossRefGoogle Scholar
  22. Ganai SA (2018) Histone deacetylase inhibitors modulating non-epigenetic players: the novel mechanism for small molecule based therapeutic intervention. Curr Drug Targets 19(6):593–601PubMedCrossRefGoogle Scholar
  23. Ganai SA, Ramadoss M, Mahadevan V (2016) Histone Deacetylase (HDAC) inhibitors – emerging roles in neuronal memory, learning, synaptic plasticity and neural regeneration. Curr Neuropharmacol 14(1):55–71PubMedCrossRefGoogle Scholar
  24. Glauser TA, Cnaan A, Shinnar S, Hirtz DG, Dlugos D, Masur D, Clark PO, Capparelli EV, Adamson PC, Childhood Absence Epilepsy Study G (2010) Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N Engl J Med 362(9):790–799PubMedPubMedCentralCrossRefGoogle Scholar
  25. Grove VE Jr, Quintanilla J, DeVaney GT (2000) Improvement of Huntington’s disease with olanzapine and valproate. N Engl J Med 343(13):973–974PubMedCrossRefGoogle Scholar
  26. Hensley K (2010) Neuroinflammation in Alzheimer’s disease: mechanisms, pathologic consequences, and potential for therapeutic manipulation. J Alzheimer’s Dis 21(1):1–14CrossRefGoogle Scholar
  27. Ikiz B, Alvarez MJ, Re DB, Le Verche V, Politi K, Lotti F, Phani S, Pradhan R, Yu C, Croft GF, Jacquier A, Henderson CE, Califano A, Przedborski S (2015) The regulatory machinery of Neurodegeneration in in vitro models of amyotrophic lateral sclerosis. Cell Rep 12(2):335–345PubMedPubMedCentralCrossRefGoogle Scholar
  28. Jiang YM, Yamamoto M, Kobayashi Y, Yoshihara T, Liang Y, Terao S, Takeuchi H, Ishigaki S, Katsuno M, Adachi H, Niwa J, Tanaka F, Doyu M, Yoshida M, Hashizume Y, Sobue G (2005) Gene expression profile of spinal motor neurons in sporadic amyotrophic lateral sclerosis. Ann Neurol 57(2):236–251PubMedCrossRefGoogle Scholar
  29. Kane RC, Bross PF, Farrell AT, Pazdur R (2003) Velcade: U.S. FDA approval for the treatment of multiple myeloma progressing on prior therapy. Oncologist 8(6):508–513PubMedCrossRefGoogle Scholar
  30. Krosschell KJ, Kissel JT, Townsend EL, Simeone SD, Zhang RZ, Reyna SP, Crawford TO, Schroth MK, Acsadi G, Kishnani PS, Von Kleist-Retzow JC, Hero B, D’Anjou G, Smith EC, Elsheikh B, Simard LR, Prior TW, Scott CB, Lasalle B, Sakonju A, Wirth B, Swoboda KJ (2018) Clinical trial of L-Carnitine and valproic acid in spinal muscular atrophy type I. Muscle Nerve 57(2):193–199PubMedCrossRefGoogle Scholar
  31. Kwan P, Brodie MJ (2000) Epilepsy after the first drug fails: substitution or add-on? Seizure Eur J Epilepsy 9(7):464–468CrossRefGoogle Scholar
  32. Kwon DY, Motley WW, Fischbeck KH, Burnett BG (2011) Increasing expression and decreasing degradation of SMN ameliorate the spinal muscular atrophy phenotype in mice. Hum Mol Genet 20(18):3667–3677PubMedPubMedCentralCrossRefGoogle Scholar
  33. Lanzillotta A, Sarnico I, Ingrassia R, Boroni F, Branca C, Benarese M, Faraco G, Blasi F, Chiarugi A, Spano P, Pizzi M (2010) The acetylation of RelA in Lys310 dictates the NF-kappaB-dependent response in post-ischemic injury. Cell Death Dis 4(1):76Google Scholar
  34. Lee CY, Fu WM, Chen CC, Su MJ, Liou HH (2008) Lamotrigine inhibits postsynaptic AMPA receptor and glutamate release in the dentate gyrus. Epilepsia 49(5):888–897PubMedCrossRefGoogle Scholar
  35. Lehar J, Krueger AS, Avery W, Heilbut AM, Johansen LM, Price ER, Rickles RJ, Short GF 3rd, Staunton JE, Jin X, Lee MS, Zimmermann GR, Borisy AA (2009) Synergistic drug combinations tend to improve therapeutically relevant selectivity. Nat Biotechnol 27(7):659–666PubMedPubMedCentralCrossRefGoogle Scholar
  36. Leng Y, Liang MH, Ren M, Marinova Z, Leeds P, Chuang DM (2008) Synergistic neuroprotective effects of lithium and valproic acid or other histone deacetylase inhibitors in neurons: roles of glycogen synthase kinase-3 inhibition. J Neurosci 28(10):2576–2588PubMedPubMedCentralCrossRefGoogle Scholar
  37. Lin CH, Lin HI, Fang JM, Cao LP, Farrer MJ, Wu RM, Chien CT, Chen CC (2017) Development of a dual inhibitor targeting HMG-CoA reductase and histone deacetylase rescues neurite degeneration in LRRK2- G2019S parkinsonism. J Neurol Sci 381:67–68CrossRefGoogle Scholar
  38. Meng J, Li Y, Camarillo C, Yao Y, Zhang Y, Xu C, Jiang L (2014) The anti-tumor histone deacetylase inhibitor SAHA and the natural flavonoid curcumin exhibit synergistic neuroprotection against amyloid-beta toxicity. PLoS One 9(1):e85570–e85570PubMedPubMedCentralCrossRefGoogle Scholar
  39. Moeller JJ, Rahey SR, Sadler RM (2009) Lamotrigine-valproic acid combination therapy for medically refractory epilepsy. Epilepsia 50(3):475–479PubMedCrossRefGoogle Scholar
  40. Musolino R, Gallitto G, De Domenico P, Bonazinga MM, Sturniolo R, Labate C, Di Perri R (1991) Synergistic anticonvulsant effect of valproic acid and ethosuximide on pentylenetetrazole-induced epileptic phenomena in rats. J Int Med Res 19(1):55–62PubMedCrossRefGoogle Scholar
  41. Narver HL, Kong L, Burnett BG, Choe DW, Bosch-Marce M, Taye AA, Eckhaus MA, Sumner CJ (2008) Sustained improvement of spinal muscular atrophy mice treated with trichostatin A plus nutrition. Ann Neurol 64(4):465–470PubMedCrossRefGoogle Scholar
  42. Pollitt SK, Pallos J, Shao J, Desai UA, Ma AA, Thompson LM, Marsh JL, Diamond MI (2003) A rapid cellular FRET assay of polyglutamine aggregation identifies a novel inhibitor. Neuron 40(4):685–694PubMedCrossRefGoogle Scholar
  43. Rossetti F, de Araujo FM, Pak T, Bailey K, Shields M, Chanda S, Addis M, Robertson BD, Moffett M, Lumley LA, Yourick DL (2012) Combined diazepam and HDAC inhibitor treatment protects against seizures and neuronal damage caused by soman exposure. Neurotoxicology 33(3):500–511PubMedCrossRefGoogle Scholar
  44. Sarhan EM, Walker MC, Selai C (2015) Evidence for efficacy of combination of antiepileptic drugs in treatment of epilepsy. J Neurol Res 5(6):267–276CrossRefGoogle Scholar
  45. Schiaffino L, Bonafede R, Scambi I, Parrella E, Pizzi M, Mariotti R (2018) Acetylation state of RelA modulated by epigenetic drugs prolongs survival and induces a neuroprotective effect on ALS murine model. Sci Rep 8(1):12875.  https://doi.org/10.1038/s41598-018-30659-4 PubMedPubMedCentralCrossRefGoogle Scholar
  46. Sharma S, Taliyan R (2015) Synergistic effects of GSK-3beta and HDAC inhibitors in intracerebroventricular streptozotocin-induced cognitive deficits in rats. Naunyn Schmiedeberg’s Arch Pharmacol 388(3):337–349CrossRefGoogle Scholar
  47. Shih TM, McDonough JH Jr, Koplovitz I (1999) Anticonvulsants for Soman-induced seizure activity1. J Biomed Sci 6(2):86–96PubMedGoogle Scholar
  48. Sittler A, Lurz R, Lueder G, Priller J, Lehrach H, Hayer-Hartl MK, Hartl FU, Wanker EE (2001) Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington’s disease. Hum Mol Genet 10(12):1307–1315PubMedCrossRefGoogle Scholar
  49. Taing KD, O’Brien TJ, Williams DA, French CR (2017) Anti-epileptic drug combination efficacy in an in vitro seizure model – phenytoin and valproate, Lamotrigine and valproate. PLoS One 12(1):e0169974–e0169974PubMedPubMedCentralCrossRefGoogle Scholar
  50. Tsai LK, Tsai MS, Lin TB, Hwu WL, Li H (2006) Establishing a standardized therapeutic testing protocol for spinal muscular atrophy. Neurobiol Dis 24(2):286–295PubMedCrossRefGoogle Scholar
  51. Zaky A, Mahmoud M, Awad D, El Sabaa BM, Kandeel KM, Bassiouny AR (2014) Valproic acid potentiates curcumin-mediated neuroprotection in lipopolysaccharide induced rats. Front Cell Neurosci 8:337–337PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Shabir Ahmad Ganai
    • 1
  1. 1.Division of Basic Sciences and Humanities, Faculty of AgricultureSKUAST-KashmirWadura SoporeIndia

Personalised recommendations