Gene therapy for Parkinson's disease: Where are we now and where are we going?

Expert Review of Neurotherapeutics

Volumn 10, Issue 12, 2010, Pages 1839-1845

  Forsayeth, John ^a   Bankiewicz, Krystof S ^a   Aminoff, Michael J ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

AAV GAD; AAV2 DDNF; AAV2 hAADC; adeno associated virus; CERE 120; gene therapy; MRI; Parkinson's disease

Indexed keywords

4 AMINOBUTYRIC ACID; ANTIPARKINSON AGENT; AROMATIC LEVO AMINO ACID DECARBOXYLASE; DOPAMINE RECEPTOR STIMULATING AGENT; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; GLUTAMATE DECARBOXYLASE; GLUTAMATE DECARBOXYLASE 65; GLUTAMATE DECARBOXYLASE 67; GUANOSINE TRIPHOSPHATE CYCLOHYDROLASE I; LEVODOPA; NEURTURIN; PARVOVIRUS VECTOR; PLACEBO; TYROSINE 3 MONOOXYGENASE;

ABSENCE OF SIDE EFFECTS; ADENO ASSOCIATED VIRUS; BRAIN DEPTH STIMULATION; BRAIN HEMORRHAGE; CLINICAL FEATURE; CLINICAL TRIAL; DRUG EFFICACY; DRUG MEGADOSE; HUMAN; LOW DRUG DOSE; NONHUMAN; PARKINSON DISEASE; REVIEW; SUBTHALAMIC NUCLEUS; TREATMENT DURATION; UNSPECIFIED SIDE EFFECT; VIRAL GENE THERAPY;

CLINICAL TRIALS AS TOPIC; DEPENDOVIRUS; FEMALE; GENE THERAPY; GENE TRANSFER TECHNIQUES; GENETIC VECTORS; HUMANS; MALE; PARKINSON DISEASE;

EID: 78649494860     PISSN: 14737175     EISSN: 17448360     Source Type: Journal    
DOI: 10.1586/ern.10.161     Document Type: Review

References (63)

1. Aposhian HV. The use of DNA for gene therapy-the need, experimental approach, and implications. Perspect. Biol. Med. 14(1), 98-108 (1970).
2. Fox MS, Littlefeld J W. Reservations concerning gene therapy. Science 173(993), 195 (1971).
3. Osterman JV, Waddell A, Aposhian HV. Gene therapy systems: the need, experimental approach, and implications. Ann. NY Acad. Sci. 179, 514-519 (1971).
4. Qasba PK, Aposhian HV. DNA and gene therapy: transfer of mouse DNA to human and mouse embryonic cells by polyoma pseudovirions. Proc. Natl Acad. Sci. USA 68(10), 2345-2349 (1971).
5. Rogers S. Gene therapy: a potentially invaluable aid to medicine and mankind. Res. Commun. Chem. Pathol. Pharmacol. 2(4), 587-600 (1971).
6. Freese E. Prospects of gene therapy. Science 175(25), 1024-1025 (1972).
7. Friedmann T, Roblin R. Gene therapy for human genetic disease? Science 175(25), 949-955 (1972).
8. Frank SA, Wilson R, Holloway RG et al. Ethics of sham surgery: perspective of patients. Mov. Disord. 23(1), 63-68 (2008).
9. Kim SY, Holloway RG, Frank S et al. Volunteering for early phase gene transfer research in Parkinson disease. Neurology 66(7), 1010-1015 (2006).
10. Ravina B, Swearingen C, Elm J, Kamp C, Kieburtz K, Kim SY. Long term understanding of study information in research participants with Parkinsons disease. Parkinsonism Relat. Disord. 16(1), 60-63 (2010).
11. Kaplitt MG, Feigin A, Tang C et al. Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, Phase I trial. Lancet 369(9579), 2097-2105 (2007).
12. Azzouz M, Martin-Rendon E, Barber RD et al. Multicistronic lentiviral vector-mediated striatal gene transfer of aromatic L-amino acid decarboxylase, tyrosine hydroxylase, and GTP cyclohydrolase I induces sustained transgene expression, dopamine production, and functional improvement in a rat model of Parkinson's disease. J. Neurosci. 22(23), 10302-10312 (2002).
13. Jarraya B, Boulet S, Ralph GS et al. Dopamine gene therapy for Parkinson's disease in a nonhuman primate without associated dyskinesia. Sci. Transl. Med. 1(2), 2ra4 (2009).
14. Perlmutter JS, Mink JW Deep brain stimulation. Annu. Rev. Neurosci. 29, 229-257 (2006).
15. Benabid AL, Chabardes S, Mitrofanis J, Pollak P. Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson's disease. Lancet Neurol. 8(1), 67-81 (2009).
16. Levy R, Lang AE, Dostrovsky JO et al. Lidocaine and muscimol microinjections in subthalamic nucleus reverse Parkinsonian symptoms. Brain 124(Pt 10), 2105-2118 (2001).
17. Chen L, Xie JX, Fung KS, Yung WH. Zolpidem modulates GABA(A) receptor function in subthalamic nucleus. Neurosci. Res. 58(1), 77-85 (2007).
18. Luo J, Kaplitt MG, Fitzsimons HL et al. Subthalamic GAD gene therapy in a Parkinson's disease rat model. Science 298(5592), 425-429 (2002).
19. Zander JF, Munster-Wandowski A, Brunk I et al. Synaptic and vesicular coexistence of VGLUT and VGAT in selected excitatory and inhibitory synapses. J. Neurosci. 30(22), 7634-7645 (2010).
20. Galvan A, Charara A, Pare JF, Levey AI, Smith Y. Differential subcellular and subsynaptic distribution of GABA(A) and GABA(B) receptors in the monkey subthalamic nucleus. Neuroscience 127(3), 709-721 (2004). (Pubitemid 38993173)
21. Erlander MG, Tillakaratne NJ, Feldblum S, Patel N, Tobin AJ. Two genes encode distinct glutamate decarboxylases. Neuron 7(1), 91-100 (1991).
22. Emborg ME, Carbon M, Holden JE et al. Subthalamic glutamic acid decarboxylase gene therapy: changes in motor function and cortical metabolism. J. Cereb. Blood Flow Metab. 27(3), 501-509 (2007).
23. Bankiewicz KS, Daadi M, Pivirotto P et al. Focal striatal dopamine may potentiate dyskinesias in parkinsonian monkeys. Exp. Neurol. 197(2), 363-372 (2006).
24. Forsayeth JR, Eberling JL, Sanftner LM et al. A dose-ranging study of AAV-hAADC therapy in parkinsonian monkeys. Mol. Ther. 14(4), 571-577 (2006).
25. Hadaczek P, Eberling JL, Pivirotto P, Bringas J, Forsayeth J, Bankiewicz KS. Eight years of clinical improvement in MPTP-lesioned primates after gene therapy with AAV2-hAADC. Mol. Ther. 18(8), 1458-1461 (2010).
26. Eberling JL, Jagust WJ, Christine CW et al. Results from a Phase I safety trial of hAAD C gene therapy for Parkinson disease. Neurology 70(21), 1980-1983 (2008).
27. Christine CW, Starr PA, Larson PS et al. Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology 73(20), 1662-1669 (2009).
28. DeJesus OT, Endres CJ, Shelton SE, Nickles RJ, Holden JE. Evaluation of fuorinated m-tyrosine analogs as PET imaging agents of dopamine nerve terminals: comparison with 6-fuoroDOPA. J. Nucl. Med. 38(4), 630-636 (1997).
29. Jordan S, Eberling JL, Bankiewicz KS et al. 6-[18F]fuoro-L-m-tyrosine: metabolism, positron emission tomography kinetics, and 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine lesions in primates. Brain Res. 750(1-2), 264-276 (1997).
30. Doudet DJ, Chan GL, Jivan S et al. Evaluation of dopaminergic presynaptic integrity: 6-[18F]fuoro-L-dopa versus 6-[18F]fuoro-L-m-tyrosine. J. Cereb. Blood Flow Metab. 19(3), 278-287 (1999).
31. Bankiewicz KS, Forsayeth J, Eberling JL et al. Long-term clinical improvement in MPTP-lesioned primates after gene therapy with AAV-hAADC. Mol. Ther. 14(4), 564-570 (2006).
32. Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260(5111), 1130-1132 (1993).
33. Baloh RH, Enomoto H, Johnson EM Jr, Milbrandt J. The GDNF family ligands and receptors-implications for neural development. Curr. Opin. Neurobiol. 10(1), 103-110 (2000).
34. Akerud P, Alberch J, Eketjall S, Wagner J, Arenas E. Differential effects of glial cell line-derived neurotrophic factor and neurturin on developing and adult substantia nigra dopaminergic neurons. J. Neurochem. 73(1), 70-78 (1999).
35. Rosenblad C, Kirik D, Devausx B, Moffat B, Phillips HS, Bjorklund A. Protection and regeneration of nigral dopaminergic neurons by neurturin or GDNF in a partial lesion model of Parkinson's disease after administration into the striatum or the lateral ventricle. Eur. J. Neurosci. 111, 1554-1566 (1999).
36. Fiandaca M, Forsayeth J, Bankiewicz K. Current status of gene therapy trials for Parkinson's disease. Exp. Neurol. 209(1), 51-57 (2008).
37. Kordower JH, Herzog CD, Dass B et al. Delivery of neurturin by AAV2 (CERE-120)-mediated gene transfer provides structural and functional neuroprotection and neurorestoration in MPTP-treated monkeys. Ann. Neurol. 60(6), 706-715 (2006).
38. Eberling JL, Kells AP, Pivirotto P et al. Functional effects of AAV2-GDNF on the dopaminergic nigrostriatal pathway in parkinsonian rhesus monkeys. Hum. Gene Ther. 20(5), 511-518 (2009).
39. Su X, Kells AP, Huang EJ et al. Safety evaluation of AAV2-GDNF gene transfer into the dopaminergic nigrostriatal pathway in aged and parkinsonian rhesus monkeys. Hum. Gene Ther. 20(12), 1627-1640 (2009).
40. Kells AP, Eberling J, Su X et al. Regeneration of the MPTP-lesioned dopaminergic system after convection-enhanced delivery of AAV2-GDNF. J. Neurosci. 30(28), 9567-9577 (2010).
41. Johnston LC, Eberling J, Pivirotto P et al. Clinically relevant effects of convection-enhanced delivery of AAV2-GDNF on the dopaminergic nigrostriatal pathway in aged rhesus monkeys. Hum. Gene Ther. 20(5), 497-510 (2009).
42. Manfredsson FP, Tumer N, Erdos B et al. Nigrostriatal rAAV-mediated GDNF over expression induces robust weight loss in a rat model of age-related obesity. Mol. Ther. 17(6), 980-991 (2009).
43. Palf 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. 22(12), 4942-4954 (2002).
44. 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 Parkinsons disease: an open-label, Phase I trial. Lancet Neurol. 7(5), 400-408 (2008).
45. Hadaczek P, Forsayeth J, Mirek H et al. Transduction of nonhuman primate brain with adeno-associated virus serotype 1: vector traffcking and immune response. Hum. Gene Ther. 20(3), 225-237 (2009).
46. Chirmule N, Xiao W, Truneh A et al. Humoral immunity to adeno-associated virus type 2 vectors following administration to murine and nonhuman primate muscle. J. Virol. 74(5), 2420-2425 (2000).
47. Sanftner LM, Suzuki BM, Doroudchi MM et al. Striatal delivery of rAAV-hAADC to rats with preexisting immunity to AAV. Mol. Ther. 9(3), 403-409 (2004).
48. Peden CS, Burger C, Muzyczka N, Mandel RJ. Circulating anti-wild-type adeno-associated virus type 2 (AAV2) antibodies inhibit recombinant AAV2 (rAAV2)-mediated, but not rAAV5-mediated, gene transfer in the brain. J. Virol. 78(12), 6344-6359 (2004).
49. Peden CS, Manfredsson FP, Reimsnider SK et al. Striatal readministration of rAAV vectors reveals an immune response against AAV2 capsids that can be circumvented. Mol. Ther. 17(3), 524-537 (2009).
50. Wright JF, Qu G, Tang C, Sommer JM. Recombinant adeno-associated virus: formulation challenges and strategies for a gene therapy vector. Curr. Opin. Drug Discov. Devel. 6(2), 174-178 (2003).
51. Hadaczek P, Yamashita Y, Mirek H et al. The 'perivascular pump' driven by arterial pulsation is a powerful mechanism for the distribution of therapeutic molecules within the brain. Mol. Ther. 14(1), 69-78 (2006).
52. Passini MA, Macauley SL, Huff MR et al. A AV vector-mediated correction of brain pathology in a mouse model of Niemann-Pick A disease. Mol. Ther. 11(5), 754-762 (2005).
53. Kaspar BK, Llado J, Sherkat N, Rothstein JD, Gage FH. Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS model. Science 301(5634), 839-842 (2003).
54. Hollis ER 2nd, Jamshidi P, Lorenzana AO et al. Transient demyelination increases the effciency of retrograde A AV transduction. Mol. Ther. 18(8), 1496-1500 (2010).
55. Arvidsson A, Kirik D, Lundberg C et al. Elevated GDNF levels following viral vector-mediated gene transfer can increase neuronal death after stroke in rats. Neurobiol. Dis. 14(3), 542-556 (2003).
56. Hadaczek P, Mirek H, Bringas J, Cunningham J, Bankiewicz K. Basic fbroblast growth factor enhances transduction, distribution, and axonal transport of adeno-associated virus type 2 vector in rat brain. Hum. Gene Ther. 15(5), 469-479 (2004).
57. Kells AP, Hadaczek P, Yin D et al. Effcient gene therapy-based method for the delivery of therapeutics to primate cortex. Proc. Natl Acad. Sci. USA 106(7), 2407-2411 (2009).
58. Krauze MT, Saito R, Noble C et al. Refux-free cannula for convection-enhanced high-speed delivery of therapeutic agents. J. Neurosurg. 103(5), 923-929 (2005).
59. Varenika V, Dickenson P, Bringas J et al. Real-time imaging of CED in the brain permits detection of infusate leakage J. Neurosurg. 109, 874-880 (2008).
60. Fiandaca MS, Varenika V, Eberling J et al. Real-time MR imaging of adeno-associated viral vector delivery to the primate brain. Neuroimage 47 (Suppl. 2), T27-T35 (2009).
61. Yin D, Valles FE, Fiandaca MS et al. Optimal region of the putamen for image-guided convection-enhanced delivery of therapeutics in human and non-human primates. Neuroimage 187(1), 46-51 (2009).
62. Yin D, Richardson RM, Fiandaca MS et al. Cannula placement for effective convection-enhanced delivery in the non-human primate thalamus and brainstem: implications for clinical delivery of therapeutics. J. Neurosurg. 113(2), 240-248 (2010).
63. ® for the Treatment of Bilateral Idiopathic Parkinson's Disease www.clinicaltrials.gov/ct2/show/NCT006 27588?term=NCT00627588&rank=1