A comprehensive approach to identifying repurposed drugs to treat SCN8A epilepsy

Epilepsia

Volumn 59, Issue 4, 2018, Pages 802-813

  Atkin, Talia A ^a   Maher, Chani M ^a   Gerlach, Aaron C ^b   Gay, Bryant C ^a   Antonio, Brett M ^b   Santos, Sonia C ^b   Padilla, Karen M ^b   Rader, JulieAnn ^a   Krafte, Douglas S ^b   Fox, Matthew A ^a   Stewart, Gregory R ^a   Petrovski, Slavé ^a,c   Devinsky, Orrin ^a,d   Might, Matthew ^a,e   Petrou, Steven ^a,c   Goldstein, David B ^a,f  

^a Pairnomix   (United States)

^b Icagen   (United States)

^c UNIVERSITY OF MELBOURNE   (Australia)

^d NEW YORK UNIVERSITY MEDICAL CENTER   (United States)

^e UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^f Department of Medicine   (United States)

Author keywords

drug library; epilepsy; precision medicine; repurposed drugs; SCN8A

Indexed keywords

AMITRIPTYLINE; ANTICONVULSIVE AGENT; CARBAMAZEPINE; CARVEDILOL; NILVADIPINE; SODIUM CHANNEL BLOCKING AGENT; SODIUM CHANNEL NAV1.6; SCN8A PROTEIN, HUMAN;

ABSENCE; ARTICLE; CELL LINE; CONCENTRATION RESPONSE; DEVELOPMENTAL DELAY; DISEASE SEVERITY; DRUG EFFECT; DRUG REPOSITIONING; ELECTROPHYSIOLOGICAL ASSAY; ELECTROPHYSIOLOGY; EPILEPSY; FEBRILE CONVULSION; GAIN OF FUNCTION MUTATION; GENE ACTIVATION; GENE EXPRESSION; GENE MUTATION; HEK293 CELL LINE; HIGH THROUGHPUT SCREENING; HUMAN; MEMBRANE POTENTIAL; NEXT GENERATION SEQUENCING; PRIORITY JOURNAL; SODIUM TRANSPORT; VOLTAGE CLAMP TECHNIQUE; WILD TYPE; CASE REPORT; CHILD; DOSE RESPONSE; FEMALE; GENETICS; MALE; MUTATION; PROCEDURES;

ANTICONVULSANTS; CHILD; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG REPOSITIONING; EPILEPSY; FEMALE; HEK293 CELLS; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; MALE; MUTATION; NAV1.6 VOLTAGE-GATED SODIUM CHANNEL;

EID: 85044398328     PISSN: 00139580     EISSN: 15281167     Source Type: Journal    
DOI: 10.1111/epi.14037     Document Type: Article

References (28)

1. Melnikova I. Rare diseases and orphan drugs. Nat Rev Drug Discov. 2012;11:267–8.
2. EpiPM Consortium. A roadmap for precision medicine in the epilepsies. Lancet Neurol. 2015;14:1219–28.
3. Caldwell JH, Schaller KL, Lasher RS, et al. Sodium channel Na(v)1.6 is localized at nodes of Ranvier, dendrites, and synapses. Proc Natl Acad Sci U S A. 2000;97:5616–20.
4. Hu W, Tian C, Li T, et al. Distinct contributions of Na(v)1.6 and Na(v)1.2 in action potential initiation and backpropagation. Nat Neurosci. 2009;12:996–1002.
5. Rush AM, Dib-Hajj SD, Waxman SG. Electrophysiological properties of two axonal sodium channels, Nav1.2 and Nav1.6, expressed in mouse spinal sensory neurones. J Physiol. 2005;564:803–15.
6. Raman IM, Sprunger LK, Meisler MH, et al. Altered subthreshold sodium currents and disrupted firing patterns in Purkinje neurons of Scn8a mutant mice. Neuron. 1997;19:881–91.
7. Smith MR, Smith RD, Plummer NW, et al. Functional analysis of the mouse Scn8a sodium channel. J Neurosci. 1998;18:6093–102.
8. Meisler MH, Helman G, Hammer MF, et al. SCN8A encephalopathy: research progress and prospects. Epilepsia. 2016;57:1027–35.
9. Wagnon JL, Barker BS, Hounshell JA, et al. Pathogenic mechanism of recurrent mutations of SCN8A in epileptic encephalopathy. Ann Clin Transl Neurol. 2016;3:114–23.
10. Carvill GL, Heavin SB, Yendle SC, et al. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. Nat Genet. 2013;45:825–30.
11. Chen MX, Gatfield K, Ward E, et al. Validation and optimization of novel high-throughput assays for human epithelial sodium channels. J Biomol Screen. 2015;20:242–53.
12. Huang CJ, Harootunian A, Maher MP, et al. Characterization of voltage-gated sodium-channel blockers by electrical stimulation and fluorescence detection of membrane potential. Nat Biotechnol. 2006;24:439–46.
13. Zhao F, Li X, Jin L, et al. Development of a rapid throughput assay for identification of hNav1.7 antagonist using unique efficacious sodium channel agonist, antillatoxin. Mar Drugs. 2016;14:1–12.
14. Zhu HL, Wassall RD, Takai M, et al. Actions of veratridine on tetrodotoxin-sensitive voltage-gated Na currents, Na1.6, in murine vas deferens myocytes. Br J Pharmacol. 2009;157:1483–93.
15. Schmalhofer WA, Calhoun J, Burrows R, et al. ProTx-II, a selective inhibitor of NaV1.7 sodium channels, blocks action potential propagation in nociceptors. Mol Pharmacol. 2008;74:1476–84.
16. Morselli PL, Baruzzi A, Gerna M, et al. Carbamazepine and carbamazepine-10, 11-epoxide concentrations in human brain. Br J Clin Pharmacol. 1977;4:535–40.
17. Riva R, Albani F, Ambrosetto G, et al. Diurnal fluctuations in free and total steady-state plasma levels of carbamazepine and correlation with intermittent side effects. Epilepsia. 1984;25:476–81.
18. Tenero D, Boike S, Boyle D, et al. Steady-state pharmacokinetics of carvedilol and its enantiomers in patients with congestive heart failure. J Clin Pharmacol. 2000;40:844–53.
19. Bart J, Dijkers EC, Wegman TD, et al. New positron emission tomography tracer [(11)C]carvedilol reveals P-glycoprotein modulation kinetics. Br J Pharmacol. 2005;145:1045–51.
20. Rosenthal J. Nilvadipine: profile of a new calcium antagonist. An overview. J Cardiovasc Pharmacol. 1994;24(suppl 2):S92–107.
21. Takakura S, Sogabe K, Satoh H, et al. Nilvadipine as a neuroprotective calcium entry blocker in a rat model of global cerebral ischemia. A comparative study with nicardipine hydrochloride. Neurosci Lett. 1992;141:199–202.
22. Ziegler VE, Co BT, Taylor JR, et al. Amitriptyline plasma levels and therapeutic response. Clin Pharmacol Ther. 1976;19:795–801.
23. Glotzbach RK, Preskorn SH. Brain concentrations of tricyclic antidepressants: single-dose kinetics and relationship to plasma concentrations in chronically dosed rats. Psychopharmacology. 1982;78:25–7.
24. Bankston JR, Kass RS. Molecular determinants of local anesthetic action of beta-blocking drugs: implications for therapeutic management of long QT syndrome variant 3. J Mol Cell Cardiol. 2010;48:246–53.
25. Barber MJ, Starmer CF, Grant AO. Blockade of cardiac sodium channels by amitriptyline and diphenylhydantoin. Evidence for two use-dependent binding sites. Circ Res. 1991;69:677–96.
26. Wang GK, Russell C, Wang SY. State-dependent block of voltage-gated Na+ channels by amitriptyline via the local anesthetic receptor and its implication for neuropathic pain. Pain. 2004;110:166–74.
27. Xie X, Lancaster B, Peakman T, et al. Interaction of the antiepileptic drug lamotrigine with recombinant rat brain type IIA Na+ channels and with native Na+ channels in rat hippocampal neurones. Pflugers Arch. 1995;430:437–46.
28. Rogawski MA, Loscher W. The neurobiology of antiepileptic drugs. Nat Rev Neurosci. 2004;5:553–64.