Bioactivity of AAV2-neurturin gene therapy (CERE-120): Differences between Parkinson's disease and nonhuman primate brains

Movement Disorders

Volumn 26, Issue 1, 2011, Pages 27-36

  Bartus, Raymond T ^a   Herzog, Christopher D ^a   Chu, Yaping ^b   Wilson, Alistair ^a   Brown, Lamar ^a   Siffert, Joao ^a   Johnson, Eugene M ^c   Olanow, C Warren ^d   Mufson, Elliott J ^b   Kordower, Jeffrey H ^b  

^a Ceregene Inc   (United States)

^b RUSH UNIVERSITY MEDICAL CENTER   (United States)

^c WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

Axonal transport; Neural repair; Neurodegeneration; Neurotrophic factors; Translational research

Indexed keywords

ADENO ASSOCIATED VIRUS SEROTYPE 2 VECTOR; ADENOVIRUS VECTOR; CERE 120; NEURTURIN; TYROSINE 3 MONOOXYGENASE; UNCLASSIFIED DRUG;

ADULT; AGED; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; AUTOPSY; CASE REPORT; CONTROLLED STUDY; CORPUS STRIATUM; DOPAMINERGIC NERVE CELL; DRUG ACTIVITY; GENE EXPRESSION; GENE THERAPY; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; NIGRONEOSTRIATAL SYSTEM; NONHUMAN; PARKINSON DISEASE; PERIKARYON; PRIMATE; PRIORITY JOURNAL; PUTAMEN; RHESUS MONKEY; SUBSTANTIA NIGRA PARS COMPACTA; VIRAL GENE DELIVERY SYSTEM;

AGED; ANIMALS; CORPUS STRIATUM; DEPENDOVIRUS; DISEASE MODELS, ANIMAL; FUNCTIONAL LATERALITY; GENE EXPRESSION REGULATION; GENE THERAPY; HUMANS; MACACA MULATTA; MALE; MIDDLE AGED; MPTP POISONING; NEURTURIN; PARKINSON DISEASE; TYROSINE 3-MONOOXYGENASE;

EID: 79951476995     PISSN: 08853185     EISSN: 15318257     Source Type: Journal    
DOI: 10.1002/mds.23442     Document Type: Article

References (37)

1. 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 1999; 73: 70-78.
2. Horger BA, Nishimura MC, Armanini MP, et al. Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons. J Neurosci 1998; 18: 4929-4937.
3. Kordower JH, Emborg ME, Bloch J, et al. Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease. Science 2000; 290: 767-773.
4. 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 2006; 60: 706-715.
5. Kordower JH, Palfi S, Chen EY, et al. Clinicopathological findings following intraventricular glial-derived neurotrophic factor treatment in a patient with Parkinson's disease. Ann Neurol 1999; 46: 419-424.
6. Nutt JG, Burchiel KJ, Comella CL, et al. Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD. Neurology 2003; 60: 69-73.
7. Lang AE, Gill S, Patel NK, et al. Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease. Ann Neurol 2006; 59: 459-466.
8. 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: 495-505.
9. Sherer TB, Fiske BK, Svendsen CN, Lang AE, Langston JW. Crossroads in GDNF therapy for Parkinson's disease. Mov Disord 2006; 21: 136-141.
10. Gasmi M, Brandon EP, Herzog CD, et al. AAV2-mediated delivery of human neurturin to the rat nigrostriatal system: long-term efficacy and tolerability of CERE-120 for Parkinson's disease. Neurobiol Dis 2007; 27: 67-76.
11. Gasmi M, Herzog CD, Brandon EP, et al. Striatal delivery of neurturin by CERE-120, an AAV2 vector for the treatment of dopaminergic neuron degeneration in Parkinson's disease. Mol Ther 2007; 15: 62-68.
12. Herzog CD, Dass B, Holden JE, et al. Striatal delivery of CERE-120, an AAV2 vector encoding human neurturin, enhances activity of the dopaminergic nigrostriatal system in aged monkeys. Mov Disord 2007; 22: 1124-1132.
13. Herzog CD, Dass B, Gasmi M, et al. Transgene expression, bioactivity, and safety of CERE-120 (AAV2-neurturin) following delivery to the monkey striatum. Mol Ther 2008; 16: 1737-1744.
14. Herzog CD, Brown L, Gammon D, et al. Expression, bioactivity, and safety 1 year after adeno-associated viral vector type 2-mediated delivery of neurturin to the monkey nigrostriatal system support cere-120 for Parkinson's disease. Neurosurgery 2009; 64: 602-612.
15. Bartus RT, Herzog CD, Bishop K, et al. Issues regarding gene therapy products for Parkinson's disease: the development of CERE-120 (AAV-NTN) as one reference point. Parkinsonism Relat Disord 2007; 13 (Suppl 3): S469-S477.
16. 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: 400-408.
17. Marks W, Bartus R, Siffert J, et al. Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomized, controlled trial. Lancet Neurol 2010;In press.
18. Eriksdotter JM, Nordberg A, Amberla K, et al. Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer's disease. Dement Geriatr Cogn Disord 1998; 9: 246-257.
19. Kirik D, Georgievska B, Bjorklund A. Localized striatal delivery of GDNF as a treatment for Parkinson disease. Nat Neurosci 2004; 7: 105-110.
20. Bjorklund A, Rosenblad C, Winkler C, Kirik D. Studies on neuroprotective and regenerative effects of GDNF in a partial lesion model of Parkinson's disease. Neurobiol Dis 1997; 4: 186-200.
21. Kirik D, Rosenblad C, Bjorklund A, Mandel RJ. Long-term rAAV-mediated gene transfer of GDNF in the rat Parkinson's model: intrastriatal but not intranigral transduction promotes functional regeneration in the lesioned nigrostriatal system. J Neurosci 2000; 20: 4686-4700.
22. Mufson EJ, Kroin JS, Sendera TJ, Sobreviela T. Distribution and retrograde transport of trophic factors in the central nervous system: functional implications for the treatment of neurodegenerative diseases. Prog Neurobiol 1999; 57: 451-484.
23. Lindsay RM, Wiegand SJ, Altar CA, DiStefano PS. Neurotrophic factors: from molecule to man. Trends Neurosci 1994; 17: 182-190.
24. Ai Y, Markesbery W, Zhang Z, et al. Intraputamenal infusion of GDNF in aged rhesus monkeys: distribution and dopaminergic effects. J Comp Neurol 2003; 461: 250-261.
25. 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. Human Gene Ther 2009; 20: 1627-1640.
26. Tomac A, Lindqvist E, Lin LF, et al. Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo. Nature 1995; 373: 335-339.
27. Kirik D, Rosenblad C, Bjorklund A. Preservation of a functional nigrostriatal dopamine pathway by GDNF in the intrastriatal 6-OHDA lesion model depends on the site of administration of the trophic factor. Eur J Neurosci 2000; 12: 3871-3882.
28. Choi-Lundberg DL, Lin Q, Schallert T, et al. Behavioral and cellular protection of rat dopaminergic neurons by an adenoviral vector encoding glial cell line-derived neurotrophic factor. Exp Neurol 1998; 154: 261-275.
29. Gash DM, Zhang Z, Ovadia A, et al. Functional recovery in parkinsonian monkeys treated with GDNF. Nature 1996; 380: 252-255.
30. Jenner P. From the MPTP-treated primate to the treatment of motor complications in Parkinson's disease. Parkinsonism Relat Disord 2009; 15 (Suppl 4): S18-S23.
31. Bartus RT. On neurodegenerative diseases, models, and treatment strategies: lessons learned and lessons forgotten a generation following the cholinergic hypothesis. Exp Neurol 2000; 163: 495-529.
32. Bartus RT. Physostigmine and recent memory: effects in young and aged nonhuman primates. Science 1979; 206: 1087-1089.
33. Chung CY, Koprich JB, Siddiqi H, Isacson O. Dynamic changes in presynaptic and axonal transport proteins combined with striatal neuroinflammation precede dopaminergic neuronal loss in a rat model of AAV alpha-synucleinopathy. J Neurosci 2009; 29: 3365-3373.
34. Roy S, Zhang B, Lee VM, Trojanowski JQ. Axonal transport defects: a common theme in neurodegenerative diseases. Acta Neuropath 2005; 109: 5-13.
35. Morfini GA, Burns M, Binder LI, et al. Axonal transport defects in neurodegenerative diseases. J Neurosci 2009; 29: 12776-12786.
36. Braak H, Sandmann-Keil D, Gai W, Braak E. Extensive axonal Lewy neurites in Parkinson's disease: a novel pathological feature revealed by alpha-synuclein immunocytochemistry. Neurosci Lett 1999; 265: 67-69.
37. De Vos KJ, Grierson AJ, Ackerley S, Miller CC. Role of axonal transport in neurodegenerative diseases. Ann Rev Neurosci 2008; 31: 151-173.