Progress and promise of antisense oligonucleotide therapeutics for central nervous system diseases

Neuropharmacology

Volumn 120, Issue , 2017, Pages 56-62

  Bishop, Kathie M ^a  

^a Otonomy   (United States)

Author keywords

Antisense oligonucleotides; CNS diseases; Drug development

Indexed keywords

ALKYLATING AGENT; ANTISENSE OLIGONUCLEOTIDE; ATAXIN 2; COPPER ZINC SUPEROXIDE DISMUTASE; HUNTINGTIN; IONIS HTTRX; ISIS SOD1RX; MESSENGER RNA; MICRORNA 155; NUSINERSEN; PLACEBO; SURVIVAL MOTOR NEURON PROTEIN 2; TRABEDERSEN; TRANSFORMING GROWTH FACTOR BETA2; UBE3A PROTEIN; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG; ANTISENSE OLIGODEOXYNUCLEOTIDE; CENTRAL NERVOUS SYSTEM AGENTS;

AMYOTROPHIC LATERAL SCLEROSIS; BLOOD BRAIN BARRIER; CENTRAL NERVOUS SYSTEM DISEASE; CONTINUOUS INFUSION; DOSE RESPONSE; DOSE TIME EFFECT RELATION; DRUG BLOOD LEVEL; DRUG CEREBROSPINAL FLUID LEVEL; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG TISSUE LEVEL; GLIOBLASTOMA; GLIOMA; HAPPY PUPPET SYNDROME; HUMAN; HUNTINGTON CHOREA; LUMBAR PUNCTURE; NONHUMAN; PHARMACODYNAMICS; PRIORITY JOURNAL; REVIEW; SINGLE DRUG DOSE; SPINAL MUSCULAR ATROPHY; SPINOCEREBELLAR DEGENERATION; SPLICING DEFECT; ANIMAL; CENTRAL NERVOUS SYSTEM DISEASES; DRUG DELIVERY SYSTEM;

ANIMALS; CENTRAL NERVOUS SYSTEM AGENTS; CENTRAL NERVOUS SYSTEM DISEASES; DRUG DELIVERY SYSTEMS; HUMANS; OLIGODEOXYRIBONUCLEOTIDES, ANTISENSE;

EID: 85009260452     PISSN: 00283908     EISSN: 18737064     Source Type: Journal    
DOI: 10.1016/j.neuropharm.2016.12.015     Document Type: Review

References (54)

1. Antisense Pharma press release: February 26, 2013. http://www.b3cnewswire.com/20130226844/antisense-pharma-announces-revised-development-path-for-trabedersen.html.
2. Apiliogullari, S., Duman, A., Gok, F., Akillioglu, I., Spinal needle design and size affect the incidence of postdural puncture headache in children. Paediatr. Anaesth. 20 (2010), 177–182.
3. Bennett, C.F., Efficiency of antisense oligonucleotide drug discovery. Antisense Nucleic Acid. Drug Dev. 12:3 (2002 Jun), 215–224.
4. Bennett, C.F., Swayze, E.E., RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu. Rev. Pharmacol. Toxicol. 50 (2010), 259–293.
5. Rx for the Treatment of Spinal Muscular Atrophy. February 2014, ASENT annual meeting, Washington, DC.
6. Bogdahn, U., Hau, P., Stockhammer, G., Venkataramana, N.K., Mahapatra, A.K., Suri, A., Balasubramaniam, A., Nair, S., Oliushine, V., Parfenov, V., Poverennova, I., Zaaroor, M., Jachimczak, P., Ludwig, S., Schmaus, S., Heinrichs, H., Schlingensiepen, K.H., Trabedersen glioma study group. Targeted therapy for high-grade glioma with the TGF-beta2 inhibitor. Trabedersen: results of a randomized and controlled phase IIb study. Neuro Oncol. 13:1 (2011 Jan), 132–142.
7. Bosco, D.A., Morfini, G., Karabacak, N.M., Song, Y., Gros-Louis, F., Pasinelli, P., Goolsby, H., Fontaine, B.A., Lemay, N., McKenna-Yasek, D., Frosch, M.P., Agar, J.N., Julien, J.P., Brady, S.T., Brown, R.H. Jr., Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS. Nat. Neurosci. 13:11 (2010), 1396–1403.
8. Butler, M., Hayes, C.S., Chappell, A., Murray, S.F., Yaksh, T.L., Hua, X.Y., Spinal distribution and metabolism of 2'-O-(2-methoxyethyl)-modified oligonucleotides after intrathecal administration in rats. Neuroscience 131:3 (2005), 705–715.
9. Butovsky, O., Jedrychowski, M.P., Cialic, R., Krasemann, S., Murugaiyan, G., Fanek, Z., Greco, D.J., Wu, P.M., Doykan, C.E., Kiner, O., Lawson, R.J., Frosch, M.P., Pochet, N., Fatimy, R.E., Krichevsky, A.M., Gygi, S.P., Lassmann, H., Berry, J., Cudkowicz, M.E., Weiner, H.L., Targeting miR-155 restores abnormal microglia and attenuates disease in SOD1 mice. Ann. Neurol. 77:1 (2015 Jan), 75–99.
10. Carroll, J.B., Warby, S.C., Southwell, A.L., Doty, C.N., Greenlee, S., Skotte, N., Hung, G., Bennett, C.F., Freier, S.M., Hayden, M.R., Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene/allele-specific silencing of mutant huntingtin. Mol. Ther. 19:12 (2011 Dec), 2178–2185.
11. Rx) in children with spinal muscular atrophy. Neurology 86:10 (2016 Mar 8), 890–897.
12. Rx in children with spinal muscular atrophy. Neurology, 82, 2014, 006 (Meeting Abstracts).
13. Darras, B.T., Spinal muscular atrophies. Pediatr. Clin. North Am. 62 (2015), 743–766.
14. Darras BT. Nusinersen in treatment-naïve patients with later-onset spinal muscular atrophy (SMA): efficacy results from a phase 1b/2a multicentre study (CS2) and its open-label extension (CS12). World Muscle Society annual meeting, Grenada, Spain. October, 2016.
15. Evers, M.M.1, Toonen, L.J.2, van Roon-Mom, W.M., Antisense oligonucleotides in therapy for neurodegenerative disorders. Adv. Drug Deliv. Rev. 87 (2015 Jun 29), 90–103.
16. Finkel, R.S., McDermott, M.P., Kaufmann, P., Darras, B.T., Chung, W.K., Sproule, D.M., Kang, P.B., Foley, A.R., Yang, M.L., Martens, W.B., Oskoui, M., Glanzman, A.M., Flickinger, J., Montes, J., Dunaway, S., O'Hagen, J., Quigley, J., Riley, S., Benton, M., Ryan, P.A., Montgomery, M., Marra, J., Gooch, C., De Vivo, D.C., Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology 83 (2014), 810–817.
17. Finkel, R.S., Chiriboga, C.A., Vajsar, J., Day, J.W., Montes, J., De Vivo, D.C., Yamashita, M., Rigo, F., Hung, G., Norris, D.A., Xia, S., Bennett, C.F., Bishop, K.M., Treatment of infantile-onset Spinal Muscular Atrophy with nusinersen: a phase 2 open-label, dose-escalation study. Lancet, December 6, 2016 (Epub ahead of print).
18. Geary, R.S., Norris, D., Yu, R., Bennett, C.F., Pharmacokinetics, biodistribution and cell uptake of antisense oligonucleotides. Adv. Drug Deliv. Rev. 87 (2015 Jun 29), 46–51.
19. Gruzman, A., Wood, W.L., Alpert, E., Prasad, M.D., Miller, R.G., Rothstein, J.D., Bowser, R., Hamilton, R., Wood, T.D., Cleveland, D.W., Lingappa, V.R., Liu, J., Common molecular signature in SOD1 for both sporadic and familial amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. U. S. A. 104:30 (2007), 12524–12529.
20. Haché, M., Swoboda, K.J., Sethna, N., Farrow-Gillespie, A., Khandji, A., Xia, S., Bishop, K.M., Intrathecal injections in children with spinal muscular atrophy: nusinersen clinical trial experience. J. Child. Neurol. 31 (2016), 899–906.
21. Hua, Y., Vickers, T.A., Baker, B.F., Bennett, C.F., Krainer, A.R., Enhancement of SMN2 exon 7 inclusion by antisense oligonucleotides targeting the exon. PLoS Biol., 5, 2007, e73.
22. Hua, Y., Sahashi, K., Hung, G., Rigo, F., Passini, M.A., Bennett, C.F., Krainer, A.R., Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model. Genes Dev. 24 (2010), 1634–1644.
23. Ionis Pharmaceuticals press release: November 7, 2016. http://ir.ionispharma.com/phoenix.zhtml?c=222170%26p=irol-newsArticle%26ID=2220037.
24. Jaschinski, F., Rothhammer, T., Jachimczak, P., Seitz, C., Schneider, A., Schlingensiepen, K.H., The antisense oligonucleotide trabedersen (AP 12009) for the targeted inhibition of TGF-β2. Curr. Pharm. Biotechnol. 12 (2011), 2203–2213.
25. Jiang, J., Zhu, Q., Gendron, T.F., Saberi, S., McAlonis-Downes, M., Seelman, A., Stauffer, J.E., Jafar-Nejad, P., Drenner, K., Schulte, D., Chun, S., Sun, S., Ling, S.C., Myers, B., Engelhardt, J., Katz, M., Baughn, M., Platoshyn, O., Marsala, M., Watt, A., Heyser, C.J., Ard, M.C., De Muynck, L., Daughrity, L.M., Swing, D.A., Tessarollo, L., Jung, C.J., Delpoux, A., Utzschneider, D.T., Hedrick, S.M., de Jong, P.J., Edbauer, D., Van Damme, P., Petrucelli, L., Shaw, C.E., Bennett, C.F., Da Cruz, S., Ravits, J., Rigo, F., Cleveland, D.W., Lagier-Tourenne, C., Gain of toxicity from ALS/FTD-linked repeat expansions in C9ORF72 is alleviated by antisense oligonucleotides targeting GGGGCC-containing RNAs. Neuron 90:3 (2016 May 4), 535–550.
26. Kay, C., Collins, J.A., Skotte, N.H., Southwell, A.L., Warby, S.C., Caron, N.S., Doty, C.N., Nguyen, B., Griguoli, A., Ross, C.J., Squitieri, F., Hayden, M.R., Huntingtin haplotypes provide prioritized target panels for allele-specific silencing in Huntington disease patients of European ancestry. Mol. Ther. 23:11 (2015 Nov), 1759–1771.
27. Keidan, I., Bielorei, B., Berkenstadt, H., Aizenkraft, A., Harel, R., Huna-Baron, R., Kaplinsky, C., Prospective evaluation of clinical and laboratory effects of intrathecal chemotherapy on children with acute leukemia. J. Pediatr. Hematol. Oncol. 27 (2005), 307–310.
28. Kishino, T., Lalande, M., Wagstaff, J., UBE3A/E6-AP mutations cause Angelman syndrome. Nat. Genet. 15:1 (1997 Jan), 70–73.
29. Kordasiewicz, H.B., Stanek, L.M., Wancewicz, E.V., Mazur, C., McAlonis, M.M., Pytel, K.A., Artates, J.W., Weiss, A., Cheng, S.H., Shihabuddin, L.S., Hung, G., Bennett, C.F., Cleveland, D.W., Sustained therapeutic reversal of Huntington's disease by transient repression of huntingtin synthesis. Neuron 74:6 (2012 Jun 21), 1031–1044.
30. Koval, E.D., Shaner, C., Zhang, P., du Maine, X., Fischer, K., Tay, J., Chau, B.N., Wu, G.F., Miller, T.M., Method for widespread microRNA-155 inhibition prolongs survival in ALS-model mice. Hum. Mol. Genet. 22:20 (2013 Oct 15), 4127–4135.
31. Kuntz, N, for the ENDEAR study group. Nusinersen treatment of infantile-onset Spinal Muscular Atrophy (SMA): Study design and initial interim efficacy and safety findings from the phase 3 ENDEAR study. World Muscle Society annual meeting, Grenada, Spain. October, 2016.
32. Lagier-Tourenne, C., Baughn, M., Rigo, F., Sun, S., Liu, P., Li, H.R., Jiang, J., Watt, A.T., Chun, S., Katz, M., Qiu, J., Sun, Y., Ling, S.C., Zhu, Q., Polymenidou, M., Drenner, K., Artates, J.W., McAlonis-Downes, M., Markmiller, S., Hutt, K.R., Pizzo, D.P., Cady, J., Harms, M.B., Baloh, R.H., Vandenberg, S.R., Yeo, G.W., Fu, X.D., Bennett, C.F., Cleveland, D.W., Ravits, J., Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration. Proc. Natl. Acad. Sci. U. S. A. 110:47 (2013 Nov 19), E4530–E4539.
33. Lee, L.C., Sennett, M., Erickson, J.M., Prevention and management of post-lumbar puncture headache in pediatric oncology patients. J. Pediatr. Oncol. Nurs. 24 (2007), 200–207.
34. Lefebvre, S., Bürglen, L., Reboullet, S., Clermont, O., Burlet, P., Viollet, L., Benichou, B., Cruaud, C., Millasseau, P., Zeviani, M., et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80 (1995), 1155–1165.
35. Lundin, K.E., Gissberg, O., Smith, C.I.E., Oligonucleotide therapies: the past and the present. Hum. Gene Ther. 26:8 (2015 Aug 1), 475–485.
36. Lunn, M.R., Wang, C.H., Spinal muscular atrophy. Lancet 371 (2008), 2120–2133.
37. Malzac, P., Webber, H., Moncla, A., Graham, J.M., Kukolich, M., Williams, C., Pagon, R.A., Ramsdell, L.A., Kishino, T., Wagstaff, J., Mutation analysis of UBE3A in Angelman syndrome patients. Am. J. Hum. Genet. 62:6 (1998 Jun), 1353–1360.
38. Meng, L., Ward, A.J., Chun, S., Bennett, C.F., Beaudet, A.L., Rigo, F., Towards a therapy for Angelman syndrome by targeting a long non-coding RNA. Nature 518:7539 (2015 Feb 19), 409–412.
39. Miller, T.M., Pestronk, A., David, W., Rothstein, J., Simpson, E., Appel, S.H., Andres, P.L., Mahoney, K., Allred, P., Alexander, K., Ostrow, L.W., Schoenfeld, D., Macklin, E.A., Norris, D.A., Manousakis, G., Crisp, M., Smith, R., Bennett, C.F., Bishop, K.M., Cudkowicz, M.E., An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. Lancet Neurol. 12 (2013), 435–442.
40. Østergaard, M.E., Southwell, A.L., Kordasiewicz, H., Watt, A.T., Skotte, N.H., Doty, C.N., Vaid, K., Villanueva, E.B., Swayze, E.E., Bennett, C.F., Hayden, M.R., Seth, P.P., Rational design of antisense oligonucleotides targeting single nucleotide polymorphisms for potent and allele selective suppression of mutant Huntingtin in the CNS. Nucleic Acids Res. 41:21 (2013 Nov), 9634–9650.
41. Passini, M.A., Bu, J., Richards, A.M., Kinnecom, C., Sardi, S.P., Stanek, L.M., Hua, Y., Rigo, F., Matson, J., Hung, G., Kaye, E.M., Shihabuddin, L.S., Krainer, A.R., Bennett, C.F., Cheng, S.H., Antisense oligonucleotides delivered to the mouse CNS ameliorate symptoms of severe spinal muscular atrophy. Sci. Transl. Med., 3, 2011, 72 ra18.
42. Pokrishevsky, E., Grad, L.I., Yousefi, M., Wang, J., Mackenzie, I.R., Cashman, N.R., Aberrant localization of FUS and TDP43 is associated with misfolding of SOD1 in amyotrophic lateral sclerosis. PLoS One, 7(4), 2012, e35050.
43. Porensky, P.N., Mitrpant, C., McGovern, V.L., Bevan, A.K., Foust, K.D., Kaspar, B.K., Wilton, S.D., Burghes, A.H., A single administration of morpholino antisense oligomer rescues spinal muscular atrophy in mouse. Hum. Mol. Genet. 21:7 (2012 Apr 1), 1625–1638.
44. Rigo, F., Chun, S.J., Norris, D.A., Hung, G., Lee, S., Matson, J., Fey, R.A., Gaus, H., Hua, Y., Grundy, J.S., Krainer, A.R., Henry, S.P., Bennett, C.F., Pharmacology of a central nervous system delivered 2'-O-methoxyethyl-modified survival of motor neuron splicing oligonucleotide in mice and nonhuman primates. J. Pharmacol. Exp. Ther. 350 (2014), 46–55.
45. Ramamoorthy, C., Geiduschek, J.M., Bratton, S.L., Miser, A.W., Miser, J.S., Postdural puncture headache in pediatric oncology patients. Clin. Pediatr. 37 (1998), 247–251.
46. Russman, B.S., Spinal muscular atrophy: clinical classification and disease heterogeneity. J. Child. Neurol. 22 (2007), 946–951.
47. Scoles, D., Schneider, M., Meera, P., Figueroa, K., Hung, G., Rigo, F., Bennett, F., Otis, T., Pulst, S., Targeting ATXN2 using antisense oligonucleotides a s a treatment for spinocerebellar ataxia type 2 (SCA2). Neurology, 78, 2016, S30.007 (Meeting abstracts).
48. Siva, K.1, Covello, G., Denti, M.A., Exon-skipping antisense oligonucleotides to correct missplicing in neurogenetic diseases. Nucleic Acid. Ther. 24:1 (2014 Feb), 69–86.
49. Smith, R.A., Miller, T.M., Yamanaka, K., Monia, B.P., Condon, T.P., Hung, G., Lobsiger, C.S., Ward, C.M., McAlonis-Downes, M., Wei, H., Wancewicz, E.V., Bennett, C.F., Cleveland, D.W., Antisense oligonucleotide therapy for neurodegenerative disease. J. Clin. Invest 116:8 (2006 Aug), 2290–2296.
50. Stanek, L.M., Yang, W., Angus, S., Sardi, P.S., Hayden, M.R., Hung, G.H., Bennett, C.F., Cheng, S.H., Shihabuddin, L.S., Antisense oligonucleotide-mediated correction of transcriptional dysregulation is correlated with behavioral benefits in the YAC128 mouse model of Huntington's disease. J. Huntingt. Dis. 2:2 (2013), 217–228.
51. Swayze, E., Powers, B., Kamme, F., Mazur, K., Wolf, D., Sullivan, J.M., Verma, A., Kinetics of ASO distribution and pharmacodynamics in the CNS after an intrathecal bolus dose in rat. Neurology, 78, 2016, S38.008 (Meeting Abstracts).
52. Turnbull, D.K., Shepherd, D.B., Post-dural puncture headache: pathogenesis, prevention and treatment. Br. J. Anaesth. 91 (2003), 718–729.
53. Whitesell, L., Geselowitz, D., Chavany, C., Fahmy, B., Walbridge, S., Alger, J.R., Neckers, L.M., Stability, clearance, and disposition of intraventricularly administered oligodeoxynucleotides: implications for therapeutic application within the central nervous system. Proc. Natl. Acad. Sci. U. S. A. 90:10 (1993 May 15), 4665–4669.
54. Zhou, H., Janghra, N., Mitrpant, C., Dickinson, R.L., Anthony, K., Price, L., Eperon, I.C., Wilton, S.D., Morgan, J., Muntoni, F., A novel morpholino oligomer targeting ISS-N1 improves rescue of severe spinal muscular atrophy transgenic mice. Hum. Gene Ther. 24:3 (2013 Mar), 331–342.