Intracerebral Hemorrhage — Fingolimod as a Treatment of Cerebral Edema After Intracerebral Hemorrhage
Citation(s)
Adeoye O, Broderick JP Advances in the management of intracerebral hemorrhage. Nat Rev Neurol. 2010 Nov;6(11):593-601. doi: 10.1038/nrneurol.2010.146. Epub 2010 Sep 28.
Ariesen MJ, Claus SP, Rinkel GJ, Algra A Risk factors for intracerebral hemorrhage in the general population: a systematic review. Stroke. 2003 Aug;34(8):2060-5. doi: 10.1161/01.STR.0000080678.09344.8D. Epub 2003 Jul 3.
Babu R, Bagley JH, Di C, Friedman AH, Adamson C Thrombin and hemin as central factors in the mechanisms of intracerebral hemorrhage-induced secondary brain injury and as potential targets for intervention. Neurosurg Focus. 2012 Apr;32(4):E8. doi: 10.3171/2012.1.FOCUS11366.
Benjamini Y, Hochberg Y Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society Series B (Methodological). 1995;57(1):289-300
Boche D, Perry VH, Nicoll JA Review: activation patterns of microglia and their identification in the human brain. Neuropathol Appl Neurobiol. 2013 Feb;39(1):3-18. doi: 10.1111/nan.12011.
Chiba K FTY720, a new class of immunomodulator, inhibits lymphocyte egress from secondary lymphoid tissues and thymus by agonistic activity at sphingosine 1-phosphate receptors. Pharmacol Ther. 2005 Dec;108(3):308-19. doi: 10.1016/j.pharmthera.2005.05.002. Epub 2005 Jun 13.
Ching T, Huang S, Garmire LX Power analysis and sample size estimation for RNA-Seq differential expression. RNA. 2014 Nov;20(11):1684-96. doi: 10.1261/rna.046011.114. Epub 2014 Sep 22.
Chun J, Hartung HP Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis. Clin Neuropharmacol. 2010 Mar-Apr;33(2):91-101. doi: 10.1097/WNF.0b013e3181cbf825.
Cohen JA, Chun J Mechanisms of fingolimod's efficacy and adverse effects in multiple sclerosis. Ann Neurol. 2011 May;69(5):759-77. doi: 10.1002/ana.22426.
Das A, Arifuzzaman S, Kim SH, Lee YS, Jung KH, Chai YG FTY720 (fingolimod) regulates key target genes essential for inflammation in microglial cells as defined by high-resolution mRNA sequencing. Neuropharmacology. 2017 Jun;119:1-14. doi: 10.1016/j.neuropharm.2017.03.034. Epub 2017 Mar 31.
David OJ, Kovarik JM, Schmouder RL Clinical pharmacokinetics of fingolimod. Clin Pharmacokinet. 2012 Jan 1;51(1):15-28. doi: 10.2165/11596550-000000000-00000.
Delbridge MS, Shrestha BM, Raftery AT, El Nahas AM, Haylor JL Reduction of ischemia-reperfusion injury in the rat kidney by FTY720, a synthetic derivative of sphingosine. Transplantation. 2007 Jul 27;84(2):187-95. doi: 10.1097/01.tp.0000269794.74990.da.
Fogelholm R, Murros K, Rissanen A, Avikainen S Long term survival after primary intracerebral haemorrhage: a retrospective population based study. J Neurol Neurosurg Psychiatry. 2005 Nov;76(11):1534-8. doi: 10.1136/jnnp.2004.055145.
Groves A, Kihara Y, Chun J Fingolimod: direct CNS effects of sphingosine 1-phosphate (S1P) receptor modulation and implications in multiple sclerosis therapy. J Neurol Sci. 2013 May 15;328(1-2):9-18. doi: 10.1016/j.jns.2013.02.011. Epub 2013 Mar 19.
Gu L, Xiong X, Zhang H, Xu B, Steinberg GK, Zhao H Distinctive effects of T cell subsets in neuronal injury induced by cocultured splenocytes in vitro and by in vivo stroke in mice. Stroke. 2012 Jul;43(7):1941-6. doi: 10.1161/STROKEAHA.112.656611. Epub 2012 Jun 7.
Hasegawa Y, Suzuki H, Sozen T, Rolland W, Zhang JH Activation of sphingosine 1-phosphate receptor-1 by FTY720 is neuroprotective after ischemic stroke in rats. Stroke. 2010 Feb;41(2):368-74. doi: 10.1161/STROKEAHA.109.568899. Epub 2009 Nov 25.
Hendrix S, Nitsch R The role of T helper cells in neuroprotection and regeneration. J Neuroimmunol. 2007 Mar;184(1-2):100-12. doi: 10.1016/j.jneuroim.2006.11.019. Epub 2007 Jan 2.
Jin Y, Zollinger M, Borell H, Zimmerlin A, Patten CJ CYP4F enzymes are responsible for the elimination of fingolimod (FTY720), a novel treatment of relapsing multiple sclerosis. Drug Metab Dispos. 2011 Feb;39(2):191-8. doi: 10.1124/dmd.110.035378. Epub 2010 Nov 2.
Keep RF, Hua Y, Xi G Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol. 2012 Aug;11(8):720-31. doi: 10.1016/S1474-4422(12)70104-7. Epub 2012 Jun 13.
Kovarik JM, Schmouder R, Barilla D, Wang Y, Kraus G Single-dose FTY720 pharmacokinetics, food effect, and pharmacological responses in healthy subjects. Br J Clin Pharmacol. 2004 May;57(5):586-91. doi: 10.1111/j.1365-2125.2003.02065.x.
Kramer A, Green J, Pollard J Jr, Tugendreich S Causal analysis approaches in Ingenuity Pathway Analysis. Bioinformatics. 2014 Feb 15;30(4):523-30. doi: 10.1093/bioinformatics/btt703. Epub 2013 Dec 13.
Lan X, Han X, Li Q, Yang QW, Wang J Modulators of microglial activation and polarization after intracerebral haemorrhage. Nat Rev Neurol. 2017 Jul;13(7):420-433. doi: 10.1038/nrneurol.2017.69. Epub 2017 May 19.
Lawson LJ, Perry VH, Dri P, Gordon S Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience. 1990;39(1):151-70. doi: 10.1016/0306-4522(90)90229-w.
Lee CW, Choi JW, Chun J Neurological S1P signaling as an emerging mechanism of action of oral FTY720 (fingolimod) in multiple sclerosis. Arch Pharm Res. 2010 Oct;33(10):1567-74. doi: 10.1007/s12272-010-1008-5. Epub 2010 Oct 30.
Liao Y, Smyth GK, Shi W featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2014 Apr 1;30(7):923-30. doi: 10.1093/bioinformatics/btt656. Epub 2013 Nov 13.
Loftspring MC, McDole J, Lu A, Clark JF, Johnson AJ Intracerebral hemorrhage leads to infiltration of several leukocyte populations with concomitant pathophysiological changes. J Cereb Blood Flow Metab. 2009 Jan;29(1):137-43. doi: 10.1038/jcbfm.2008.114. Epub 2008 Oct 1.
Love MI, Huber W, Anders S Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550. doi: 10.1186/s13059-014-0550-8.
Lu L, Barfejani AH, Qin T, Dong Q, Ayata C, Waeber C Fingolimod exerts neuroprotective effects in a mouse model of intracerebral hemorrhage. Brain Res. 2014 Mar 25;1555:89-96. doi: 10.1016/j.brainres.2014.01.048. Epub 2014 Feb 3.
Man K, Ng KT, Lee TK, Lo CM, Sun CK, Li XL, Zhao Y, Ho JW, Fan ST FTY720 attenuates hepatic ischemia-reperfusion injury in normal and cirrhotic livers. Am J Transplant. 2005 Jan;5(1):40-9. doi: 10.1111/j.1600-6143.2004.00642.x. Erratum In: Am J Transplant. 2017 Mar;17 (3):845.
Mao LL, Yuan H, Wang WW, Wang YJ, Yang MF, Sun BL, Zhang ZY, Yang XY Adoptive Regulatory T-cell Therapy Attenuates Perihematomal Inflammation in a Mouse Model of Experimental Intracerebral Hemorrhage. Cell Mol Neurobiol. 2017 Jul;37(5):919-929. doi: 10.1007/s10571-016-0429-1. Epub 2016 Sep 27.
Melendez AJ Sphingosine kinase signalling in immune cells: potential as novel therapeutic targets. Biochim Biophys Acta. 2008 Jan;1784(1):66-75. doi: 10.1016/j.bbapap.2007.07.013. Epub 2007 Aug 14.
Mendelow AD, Gregson BA, Rowan EN, Murray GD, Gholkar A, Mitchell PM; STICH II Investigators Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet. 2013 Aug 3;382(9890):397-408. doi: 10.1016/S0140-6736(13)60986-1. Epub 2013 May 29. Erratum In: Lancet. 2013 Aug 3;382(9890):396. Lancet. 2021 Sep 18;398(10305):1042.
Mracsko E, Veltkamp R Neuroinflammation after intracerebral hemorrhage. Front Cell Neurosci. 2014 Nov 20;8:388. doi: 10.3389/fncel.2014.00388. eCollection 2014.
Nayak D, Huo Y, Kwang WX, Pushparaj PN, Kumar SD, Ling EA, Dheen ST Sphingosine kinase 1 regulates the expression of proinflammatory cytokines and nitric oxide in activated microglia. Neuroscience. 2010 Mar 10;166(1):132-44. doi: 10.1016/j.neuroscience.2009.12.020. Epub 2009 Dec 28.
Noda H, Takeuchi H, Mizuno T, Suzumura A Fingolimod phosphate promotes the neuroprotective effects of microglia. J Neuroimmunol. 2013 Mar 15;256(1-2):13-8. doi: 10.1016/j.jneuroim.2012.12.005. Epub 2013 Jan 3.
Okada T, Kajimoto T, Jahangeer S, Nakamura S Sphingosine kinase/sphingosine 1-phosphate signalling in central nervous system. Cell Signal. 2009 Jan;21(1):7-13. doi: 10.1016/j.cellsig.2008.07.011. Epub 2008 Jul 22.
Qin C, Fan WH, Liu Q, Shang K, Murugan M, Wu LJ, Wang W, Tian DS Fingolimod Protects Against Ischemic White Matter Damage by Modulating Microglia Toward M2 Polarization via STAT3 Pathway. Stroke. 2017 Dec;48(12):3336-3346. doi: 10.1161/STROKEAHA.117.018505. Epub 2017 Nov 7.
Taylor RA, Sansing LH Microglial responses after ischemic stroke and intracerebral hemorrhage. Clin Dev Immunol. 2013;2013:746068. doi: 10.1155/2013/746068. Epub 2013 Oct 10.
Tham CS, Lin FF, Rao TS, Yu N, Webb M Microglial activation state and lysophospholipid acid receptor expression. Int J Dev Neurosci. 2003 Dec;21(8):431-43. doi: 10.1016/j.ijdevneu.2003.09.003.
van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol. 2010 Feb;9(2):167-76. doi: 10.1016/S1474-4422(09)70340-0. Epub 2010 Jan 5.
Wang J, Dore S Inflammation after intracerebral hemorrhage. J Cereb Blood Flow Metab. 2007 May;27(5):894-908. doi: 10.1038/sj.jcbfm.9600403. Epub 2006 Oct 11.
Wang J Preclinical and clinical research on inflammation after intracerebral hemorrhage. Prog Neurobiol. 2010 Dec;92(4):463-77. doi: 10.1016/j.pneurobio.2010.08.001. Epub 2010 Aug 14.
Wasserman JK, Zhu X, Schlichter LC Evolution of the inflammatory response in the brain following intracerebral hemorrhage and effects of delayed minocycline treatment. Brain Res. 2007 Nov 14;1180:140-54. doi: 10.1016/j.brainres.2007.08.058. Epub 2007 Sep 5.
Xi G, Keep RF, Hoff JT Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 2006 Jan;5(1):53-63. doi: 10.1016/S1474-4422(05)70283-0.
Xiong XY, Liu L, Yang QW Functions and mechanisms of microglia/macrophages in neuroinflammation and neurogenesis after stroke. Prog Neurobiol. 2016 Jul;142:23-44. doi: 10.1016/j.pneurobio.2016.05.001. Epub 2016 May 7.
Yilmaz G, Arumugam TV, Stokes KY, Granger DN Role of T lymphocytes and interferon-gamma in ischemic stroke. Circulation. 2006 May 2;113(17):2105-12. doi: 10.1161/CIRCULATIONAHA.105.593046. Epub 2006 Apr 24.
Zhang Z, Zhang Z, Lu H, Yang Q, Wu H, Wang J Microglial Polarization and Inflammatory Mediators After Intracerebral Hemorrhage. Mol Neurobiol. 2017 Apr;54(3):1874-1886. doi: 10.1007/s12035-016-9785-6. Epub 2016 Feb 19.
Zhao H, Garton T, Keep RF, Hua Y, Xi G Microglia/Macrophage Polarization After Experimental Intracerebral Hemorrhage. Transl Stroke Res. 2015 Dec;6(6):407-9. doi: 10.1007/s12975-015-0428-4. Epub 2015 Oct 7. No abstract available.
Zhou Y, Wang Y, Wang J, Anne Stetler R, Yang QW Inflammation in intracerebral hemorrhage: from mechanisms to clinical translation. Prog Neurobiol. 2014 Apr;115:25-44. doi: 10.1016/j.pneurobio.2013.11.003. Epub 2013 Nov 26.
Zollinger M, Gschwind HP, Jin Y, Sayer C, Zecri F, Hartmann S Absorption and disposition of the sphingosine 1-phosphate receptor modulator fingolimod (FTY720) in healthy volunteers: a case of xenobiotic biotransformation following endogenous metabolic pathways. Drug Metab Dispos. 2011 Feb;39(2):199-207. doi: 10.1124/dmd.110.035907. Epub 2010 Nov 2.
Fingolimod as a Treatment of Cerebral Edema After Intracerebral Hemorrhage
Interventional studies are often prospective and are specifically tailored to evaluate direct impacts of treatment or preventive measures on disease.
Observational studies are often retrospective and are used to assess potential causation in exposure-outcome relationships and therefore influence preventive methods.
Expanded access is a means by which manufacturers make investigational new drugs available, under certain circumstances, to treat a patient(s) with a serious disease or condition who cannot participate in a controlled clinical trial.
Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.
Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.