1,381
Views
18
CrossRef citations to date
0
Altmetric
Review

Gene therapy for Parkinson’s disease: contemporary practice and emerging concepts

, , &
Pages 577-590 | Received 02 Mar 2020, Accepted 29 Apr 2020, Published online: 19 May 2020

References

  • Pringsheim T, Jette N, Frolkis A, et al. The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2014;29(13):1583–1590. .
  • Marras C, Beck JC, Bower JH, et al. Prevalence of Parkinson’s disease across North America. NPJ Parkinsons Dis. 2018;4(1):21. .
  • Espay AJ, Morgante F, Merola A, et al. Levodopa-induced dyskinesia in Parkinson disease: current and evolving concepts. Ann Neurol. 2018;84(6):797–811. .
  • Jankovic J. Levodopa strengths and weaknesses. Neurology. 2002;58(Supplement 1):S19–S32.
  • Merola A, Zibetti M, Angrisano S, et al. Comparison of subthalamic nucleus deep brain stimulation and Duodopa in the treatment of advanced Parkinson’s disease. Mov Disord. 2011;26(4):664–670.
  • Borel F, Kay MA, Mueller C. Recombinant AAV as a platform for translating the therapeutic potential of RNA interference. Mol Ther. 2014;22(4):692–701.
  • Han H, Yang J, Chen W, et al. A comprehensive review on histone-mediated transfection for gene therapy. Biotechnol Adv. 2019;37(1):132–144. .
  • Haggerty DL, Grecco GG, Reeves KC, et al. Adeno-associated viral vectors in neuroscience research. Mol Ther Methods Clin Dev. 2019;17:69–82.
  • Hudry E, Vandenberghe LH. Therapeutic AAV gene transfer to the nervous system: a clinical reality. Neuron. 2019;101(5):839–862.
  • Hastie E, Samulski RJ. Adeno-associated virus at 50: a golden anniversary of discovery, research, and gene therapy success–a personal perspective. Hum Gene Ther. 2015;26(5):257–265.
  • Cearley CN, Wolfe JH. A single injection of an adeno-associated virus vector into nuclei with divergent connections results in widespread vector distribution in the brain and global correction of a neurogenetic disease. J Neurosci. 2007;27(37):9928–9940.
  • Hanlon KS, Meltzer JC, Buzhdygan T, et al. Selection of an efficient AAV vector for robust CNS transgene expression. Mol Ther Methods Clin Dev. 2019;15:320–332.
  • Rosario AM, Cruz PE, Ceballos-Diaz C, et al. Microglia-specific targeting by novel capsid-modified AAV6 vectors. Mol Ther Methods Clin Dev. 2016;3:16026.
  • Berns KI, Muzyczka N. AAV: an overview of unanswered questions. Hum Gene Ther. 2017;28(4):308–313.
  • Gao G, Vandenberghe LH, Wilson JM. New recombinant serotypes of AAV vectors. Curr Gene Ther. 2005;5(3):285–297.
  • Christine CW, Bankiewicz KS, Van Laar AD, et al., Magnetic resonance imaging–guided phase 1 trial of putaminal AADC gene therapy for Parkinson’s disease. Ann Neurol. 2019;85(5): 704–714. .
  • Naldini L, Blömer U, Gallay P, et al. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science. 1996;272(5259):263–267. .
  • Palfi S, Leventhal L, Chu Y, et al. Lentivirally delivered glial cell line-derived neurotrophic factor increases the number of striatal dopaminergic neurons in primate models of nigrostriatal degeneration. J Neurosci. 2002;22(12):4942–4954. .
  • Miyoshi H, Blömer U, Takahashi M, et al. Development of a self-inactivating lentivirus vector. J Virol. 1998;72(10):8150–8157. .
  • Zufferey R, Dull T, Mandel RJ, et al. Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J Virol. 1998;72(12):9873–9880. .
  • Tambasco N, Romoli M, Calabresi P. Levodopa in parkinson’s disease: current status and future developments. Curr Neuropharmacol. 2018;16(8):1239–1252.
  • Bankiewicz KS, Eberling JL, Kohutnicka M, et al., Convection-enhanced delivery of AAV vector in parkinsonian monkeys; in vivo detection of gene expression and restoration of dopaminergic function using pro-drug approach. Exp Neurol. 2000;164(1): 2–14. .
  • Christine CW, Starr PA, Larson PS, et al., Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology. 2009;73(20): 1662–1669. .
  • Muramatsu S, Fujimoto K, Kato S, et al. A phase I study of aromatic L-amino acid decarboxylase gene therapy for Parkinson’s disease. Mol Ther. 2010;18(9):1731–1735. .
  • Armstrong MJ, Okun MS. Diagnosis and treatment of Parkinson disease: a review. JAMA. 2020;323(6):548–560.
  • Palfi S, Gurruchaga JM, Ralph GS, et al. Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson’s disease: a dose escalation, open-label, phase 1/2 trial. Lancet. 2014;383(9923):1138–1146.
  • Kells AP, Eberling J, Su X, et al., Regeneration of the MPTP-lesioned dopaminergic system after convection-enhanced delivery of AAV2-GDNF. J Neurosci. 2010;30(28): 9567–9577. .
  • Pascual A, Hidalgo-Figueroa M, Gómez-Díaz R, et al. GDNF and protection of adult central catecholaminergic neurons. J Mol Endocrinol. 2011;46(3):R83–R92.
  • Richardson RM, Kells AP, Rosenbluth KH, et al. Interventional MRI-guided putaminal delivery of AAV2-GDNF for a planned clinical trial in Parkinson’s disease. Mol Ther. 2011;19(6):1048–1057.
  • Gash DM, Zhang Z, Ovadia A, et al. Functional recovery in parkinsonian monkeys treated with GDNF. Nature. 1996;380(6571):252–255.
  • Tomac A, Lindqvist E, Lin LF, et al. Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo. Nature. 1995;373(6512):335–339. .
  • Gill SS, Patel NK, Hotton GR, et al. Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat Med. 2003;9(5):589–595.
  • Heiss JD, Lungu C, Hammoud DA, et al., Trial of magnetic resonance-guided putaminal gene therapy for advanced Parkinson’s disease. Mov Disord. 2019;34(7): 1073–1078. .
  • Whone A, Luz M, Boca M, et al. Randomized trial of intermittent intraputamenal glial cell line-derived neurotrophic factor in Parkinson’s disease. Brain. 2019;142(3):512–525. .
  • Whone AL, Boca M, Luz M, et al. Extended treatment with glial cell line-derived neurotrophic factor in Parkinson’s disease. J Parkinsons Dis. 2019;9(2):301–313. .
  • Kotzbauer PT, Lampe PA, Heuckeroth RO, et al. Neurturin, a relative of glial-cell-line-derived neurotrophic factor. Nature. 1996;384(6608):467–470.
  • Marks WJ Jr, Ostrem JL, Verhagen L, et al., Safety and tolerability of intraputaminal delivery of CERE-120 (adeno-associated virus serotype 2-neurturin) to patients with idiopathic Parkinson’s disease: an open-label, phase I trial. Lancet Neurol. 2008;7(5): 400–408. .
  • Marks WJ Jr, Bartus RT, Siffert J, et al., Gene delivery of AAV2-neurturin for Parkinson’s disease: a double-blind, randomised, controlled trial. Lancet Neurol. 2010;9(12): 1164–1172. .
  • Olanow C, Bartus RT, Baumann TL, et al., Gene delivery of neurturin to putamen and substantia nigra in Parkinson disease: A double-blind, randomized, controlled trial. Ann Neurol. 2015;78(2): 248–257. .
  • Gatto EM, Da Prat G, Etcheverry JL, et al. Parkinsonisms and glucocerebrosidase deficiency: a comprehensive review for molecular and cellular mechanism of glucocerebrosidase deficiency. Brain Sci. 2019;9(2):30.
  • Rocha EM, Smith GA, Park E, et al. Glucocerebrosidase gene therapy prevents α-synucleinopathy of midbrain dopamine neurons. Neurobiol Dis. 2015;82:495–503.
  • Morabito G, Giannelli SG, Ordazzo G, et al. AAV-PHP.B-mediated global-scale expression in the mouse nervous system enables GBA1 gene therapy for wide protection from synucleinopathy. Mol Ther. 2017;25(12):2727–2742. .
  • Erlander MG, Tillakaratne NJ, Feldblum S, et al. Two genes encode distinct glutamate decarboxylases. Neuron. 1991;7(1):91–100. .
  • LeWitt PA, Rezai AR, Leehey MA, et al., AAV2-GAD gene therapy for advanced Parkinson’s disease: a double-blind, sham-surgery controlled, randomised trial. Lancet Neurol. 2011;10(4): 309–319. .
  • Niethammer M, Tang CC, LeWitt PA, et al. Long-term follow-up of a randomized AAV2-GAD gene therapy trial for Parkinson’s disease. JCI Insight. 2017;2(7):e90133. .
  • Niethammer M, Tang CC, Vo A, et al. Gene therapy reduces Parkinson’s disease symptoms by reorganizing functional brain connectivity. Sci Transl Med. 2018;10(469):eaau0713. .
  • Hinderer C, Bell P, Katz N, et al. Evaluation of intrathecal routes of administration for adeno-associated viral vectors in large animals. Hum Gene Ther. 2018;29(1):15–24. .
  • Salvatore MF, Ai Y, Fischer B, et al. Point source concentration of GDNF may explain failure of phase II clinical trial. Exp Neurol. 2006;202(2):497–505. .
  • Aly AE, Harmon BT, Padegimas L, et al. Intranasal delivery of pGDNF DNA nanoparticles provides neuroprotection in the rat 6-hydroxydopamine model of parkinson’s disease. Mol Neurobiol. 2019;56(1):688–701. .
  • Hadaczek P, Mirek H, Bringas J, et al. Basic fibroblast growth factor enhances transduction, distribution, and axonal transport of adeno-associated virus type 2 vector in rat brain. Hum Gene Ther. 2004;15(5):469–479. .
  • Bravo-Hernandez M, Tadokoro T, Navarro MR, et al. Spinal subpial delivery of AAV9 enables widespread gene silencing and blocks motoneuron degeneration in ALS. Nat Med. 2020;26(1):118–130.
  • Yager LM, Garcia AF, Wunsch AM, et al. The ins and outs of the striatum: role in drug addiction. Neuroscience. 2015;301:529–541.
  • Eberling JL, Jagust WJ, Christine CW, et al. Results from a phase I safety trial of hAADC gene therapy for Parkinson disease. Neurology. 2008;70(21):1980–1983. .
  • Fiandaca MS, Varenika V, Eberling J, et al. Real-time MR imaging of adeno-associated viral vector delivery to the primate brain. Neuroimage. 2009;47(Suppl 2):T27–T35. .
  • Hadaczek P, Kohutnicka M, Krauze MT, et al. Convection-enhanced delivery of adeno-associated virus type 2 (AAV2) into the striatum and transport of AAV2 within monkey brain. Hum Gene Ther. 2006;17(3):291–302. .
  • Richardson RM, Kells AP, Martin AJ, et al. Novel platform for MRI-guided convection-enhanced delivery of therapeutics: preclinical validation in nonhuman primate brain. Stereotact Funct Neurosurg. 2011;89(3):141–151. .
  • Chittiboina P, Heiss JD, Lonser RR. Accuracy of direct magnetic resonance imaging-guided placement of drug infusion cannulae. J Neurosurg. 2015;122(5):1173–1179.
  • Bobo RH, Laske DW, Akbasak A, et al. Convection-enhanced delivery of macromolecules in the brain. Proc Natl Acad Sci U S A. 1994;91(6):2076–2080. .
  • Morrison PF, Laske DW, Bobo H, et al. High-flow microinfusion: tissue penetration and pharmacodynamics. Am J Physiol. 1994;266(1 Pt 2):R292–R305. .
  • Hamilton JF, Morrison PF, Chen MY, et al. Heparin coinfusion during convection-enhanced delivery (CED) increases the distribution of the glial-derived neurotrophic factor (GDNF) ligand family in rat striatum and enhances the pharmacological activity of neurturin. Exp Neurol. 2001;168(1):155–161.
  • Bankiewicz KS, Sudhakar V, Samaranch L, et al. AAV viral vector delivery to the brain by shape-conforming MR-guided infusions. J Control Release. 2016;240:434–442.
  • Sudhakar V, Naidoo J, Samaranch L, et al. Infuse-as-you-go convective delivery to enhance coverage of elongated brain targets: technical note. J Neurosurg. 2019:1–8. 10.3171/2019.4.JNS19826
  • Ciesielska A, Mittermeyer G, Hadaczek P, et al. Anterograde axonal transport of AAV2-GDNF in rat basal ganglia. Mol Ther. 2011;19(5):922–927. .
  • San Sebastian W, Samaranch L, Heller G, et al. Adeno-associated virus type 6 is retrogradely transported in the non-human primate brain. Gene Ther. 2013;20(12):1178–1183. .
  • Zingg B, Chou XL, Zhang ZG, et al. AAV-mediated anterograde transsynaptic tagging: mapping corticocollicular input-defined neural pathways for defense behaviors. Neuron. 2017;93(1):33–47. .
  • Kells AP, Forsayeth J, Bankiewicz KS. Glial-derived neurotrophic factor gene transfer for Parkinson’s disease: anterograde distribution of AAV2 vectors in the primate brain. Neurobiol Dis. 2012;48(2):228–235.
  • Parashos SA, Luo S, Biglan KM, et al. Measuring disease progression in early Parkinson disease: the National institutes of health exploratory trials in Parkinson Disease (NET-PD) experience. JAMA Neurol. 2014;71(6):710–716. .
  • Merola A, Sturchio A, Hacker S, et al. Technology-based assessment of motor and nonmotor phenomena in Parkinson disease. Expert Rev Neurother. 2018;18(11):825–845. .
  • Nandhagopal R, Kuramoto L, Schulzer M, et al. Longitudinal progression of sporadic Parkinson’s disease: a multi-tracer positron emission tomography study. Brain. 2009;132(11):2970–2979. .
  • Eshuis SA, Maguire RP, Leenders KL, et al. Comparison of FP-CIT SPECT with F-DOPA PET in patients with de novo and advanced Parkinson’s disease. Eur J Nucl Med Mol Imaging. 2006;33(2):200–209. .
  • Ribeiro MJ, Vidailhet M, Loc’h C, et al. Dopaminergic function and dopamine transporter binding assessed with positron emission tomography in Parkinson disease. Arch Neurol. 2002;59(4):580–586. .
  • Benamer HT, Patterson J, Wyper DJ, et al. Correlation of Parkinson’s disease severity and duration with 123I-FP-CIT SPECT striatal uptake. Mov Disord. 2000;15(4):692–698. .
  • Pavese N, Rivero-Bosch M, Lewis SJ, et al. Progression of monoaminergic dysfunction in Parkinson’s disease: a longitudinal 18F-dopa PET study. Neuroimage. 2011;56(3):1463–1468. .
  • Abi-Dargham A, Gandelman MS, DeErausquin GA, et al. SPECT imaging of dopamine transporters in human brain with iodine-123-fluoroalkyl analogs of beta-CIT. J Nucl Med. 1996;37(7):1129–1133.
  • Kish SJ, Furukawa Y, Chang LJ, et al. Regional distribution of serotonin transporter protein in postmortem human brain: is the cerebellum a SERT-free brain region? Nucl Med Biol. 2005;32(2):123–128. .
  • Pirker W, Holler I, Gerschlager W, et al. Measuring the rate of progression of Parkinson’s disease over a 5-year period with beta-CIT SPECT. Mov Disord. 2003;18(11):1266–1272. .
  • Brück A, Aalto S, Rauhala E, et al. A follow-up study on 6-[18 F]fluoro-L-dopa uptake in early Parkinson’s disease shows nonlinear progression in the putamen. Mov Disord. 2009;24(7):1009–1015. .
  • Morrish PK, Sawle GV, Brooks DJ. An [18 F]dopa–PET and clinical study of the rate of progression in Parkinson’s disease. Brain. 1996;119(2):585–591.
  • Whone AL, Watts RL, Stoessl AJ, et al. Slower progression of Parkinson’s disease with ropinirole versus levodopa: the REAL-PET study. Ann Neurol. 2003;54(1):93–101. .
  • Chalon S, Vercouillie J, Payoux P, et al. The story of the dopamine transporter PET Tracer LBT-999: from conception to clinical use. Front Med (Lausanne). 2019;6:90.
  • Fu JF, Klyuzhin I, McKenzie J, et al. Joint pattern analysis applied to PET DAT and VMAT2 imaging reveals new insights into Parkinson’s disease induced presynaptic alterations. Neuroimage Clin. 2019;23:101856.
  • Kramer V, Juri C, Riss PJ, et al. Pharmacokinetic evaluation of [(18)F]PR04.MZ for PET/CT imaging and quantification of dopamine transporters in the human brain. Eur J Nucl Med Mol Imaging. 2019. Epub ahead of print. 10.1007/s00259-019-04594-z.
  • Amado D, Mingozzi F, Hui D, et al. Safety and efficacy of subretinal readministration of a viral vector in large animals to treat congenital blindness. Sci Transl Med. 2010;2(21):21ra16. .
  • Forrester JV, McMenamin PG, Dando SJ. CNS infection and immune privilege. Nat Rev Neurosci. 2018;19(11):655–671.
  • Mingozzi F, High KA. Overcoming the host immune response to adeno-associated virus gene delivery vectors: the race between clearance, tolerance, neutralization, and escape. Annu Rev Virol. 2017;4(1):511–534.
  • Meliani A, Boisgerault F, Hardet R, et al. Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration. Nat Commun. 2018;9(1):4098. .
  • Schnepp BC, Jensen RL, Chen CL, et al. Characterization of adeno-associated virus genomes isolated from human tissues. J Virol. 2005;79(23):14793–14803. .
  • Nakai H, Montini E, Fuess S, et al. Helper-independent and AAV-ITR-independent chromosomal integration of double-stranded linear DNA vectors in mice. Mol Ther. 2003;7(1):101–111. .
  • Castle MJ, Turunen HT, Vandenberghe LH, et al. Controlling AAV tropism in the nervous system with natural and engineered capsids. Methods Mol Biol. 2016;1382:133–149.
  • Kanaan NM, Sellnow RC, Boye SL, et al. Rationally Engineered AAV capsids improve transduction and volumetric spread in the CNS. Mol Ther Nucleic Acids. 2017;8:184–197.
  • Tordo J, O’Leary C, Antunes ASLM, et al. A novel adeno-associated virus capsid with enhanced neurotropism corrects a lysosomal transmembrane enzyme deficiency. Brain. 2018;141(7):2014–2031. .
  • Naidoo J, Stanek LM, Ohno K, et al. Extensive transduction and enhanced spread of a modified AAV2 capsid in the non-human primate CNS. Mol Ther. 2018;26(10):2418–2430.
  • Tervo DG, Hwang BY, Viswanathan S, et al. A designer AAV variant permits efficient retrograde access to projection neurons. Neuron. 2016;92(2):372–382.
  • Jackson KL, Dayton RD, Deverman BE, et al. Corrigendum: better targeting, better efficiency for wide-scale neuronal transduction with the synapsin promoter and AAV-PHP.B. Front Mol Neurosci. 2016;9:154.
  • McLean JR, Smith GA, Rocha EM, et al. Widespread neuron-specific transgene expression in brain and spinal cord following synapsin promoter-driven AAV9 neonatal intracerebroventricular injection. Neurosci Lett. 2014;576:73–78.
  • Watakabe A, Ohtsuka M, Kinoshita M, et al. Comparative analyses of adeno-associated viral vector serotypes 1, 2, 5, 8 and 9 in marmoset, mouse and macaque cerebral cortex. Neurosci Res. 2015;93:144–157.
  • Dashkoff J, Lerner EP, Truong N, et al. Tailored transgene expression to specific cell types in the central nervous system after peripheral injection with AAV9. Mol Ther Methods Clin Dev. 2016;3:16081.
  • Georgiou E, Sidiropoulou K, Richter J, et al. Gene therapy targeting oligodendrocytes provides therapeutic benefit in a leukodystrophy model. Brain. 2017;140(3):599–616. .
  • Kennedy LH, Rinholm JE. Visualization and live imaging of oligodendrocyte organelles in organotypic brain slices using adeno-associated virus and confocal microscopy. J Vis Exp. 2017;128:56237.
  • Di Maio R, Hoffman EK, Rocha EM, et al. LRRK2 activation in idiopathic Parkinson’s disease. Sci Transl Med. 2018;10(451):eaar5429.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.