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

The Lancet

Volumn 383, Issue 9923, 2014, Pages 1138-1146

  Palfi, Stéphane ^a,b   Gurruchaga, Jean Marc ^a,b   Scott Ralph, G ^e   Lepetit, Helene ^a,b   Lavisse, Sonia ^d   Buttery, Philip C ^f   Watts, Colin ^f   Miskin, James ^e   Kelleher, Michelle ^e   Deeley, Sarah ^e   Iwamuro, Hirokazu ^a,b   Lefaucheur, Jean Pascal ^a,b   Thiriez, Claire ^a,b   Fenelon, Gilles ^a,b,c   Lucas, Cherry ^e   Brugières, Pierre ^a,b   Gabriel, Inanna ^a,b   Abhay, Kou ^a,b   Drouot, Xavier ^a,b   Tani, Naoki ^a,b   Kas, Aurelie ^d   Ghaleh, Bijan ^a,b   Le Corvoisier, Philippe ^a,b   Dolphin, Patrice ^a,b   Breen, David P ^f   Mason, Sarah ^f   Guzman, Natalie Valle ^f   Mazarakis, Nicholas D ^g   Radcliffe, Pippa A ^e   Harrop, Richard ^e   Kingsman, Susan M ^e   Rascol, Olivier ^h   Naylor, Stuart ^e   Barker, Roger A ^f   Hantraye, Philippe ^d   Remy, Philippe ^a,b,d   Cesaro, Pierre ^a,b,c   Mitrophanous, Kyriacos A ^e   more..

^a HENRI MONDOR HOSPITAL   (France)

^b FACULTÉ DE MÉDECINE   (France)

^c INSERM U955   (France)

^d SERVICE HOSPITALIER FRÉDÉRIC JOLIOT   (France)

^e OXFORD BIOMEDICA UK LTD   (United Kingdom)

^f UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^g HAMMERSMITH HOSPITAL   (United Kingdom)

^h INSERM   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIPARKINSON AGENT; LENTIVIRUS VECTOR; LEVODOPA; PROSAVIN; UNCLASSIFIED DRUG; DOPAMINE;

ABNORMAL DREAMING; ADULT; AKINESIA; ANXIETY; ARTICLE; BALANCE DISORDER; BRAIN DEPTH STIMULATION; BRAIN EDEMA; CLINICAL ARTICLE; CONFUSION; CONNECTIVE TISSUE DISEASE; DELUSIONAL DISORDER; DISEASE DURATION; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG SAFETY; DRUG TOLERABILITY; DYSARTHRIA; DYSKINESIA; FEMALE; FRANCE; GENE TRANSFER; HALLUCINATION; HEADACHE; HUMAN; LONG TERM CARE; MALE; MIDDLE AGED; MOTOR DYSFUNCTION; MUSCULOSKELETAL PAIN; MYALGIA; NEUROLOGIC DISEASE; NEUROPSYCHOLOGICAL TEST; NUCLEAR MAGNETIC RESONANCE IMAGING; ON OFF PHENOMENON; OPEN STUDY; PARKINSON DISEASE; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; SPEECH DISORDER; SUBDURAL HEMATOMA; TRANSIENT TRANSFECTION; TREMOR; UNIFIED PARKINSON DISEASE RATING SCALE; UNSPECIFIED SIDE EFFECT; VIRAL GENE THERAPY; WEIGHT GAIN; WEIGHT REDUCTION; AGED; CONTROLLED STUDY; DRUG EFFICACY; FOLLOW UP; GENE THERAPY; PUTAMEN;

AGED; ANTIPARKINSON AGENTS; DOPA DECARBOXYLASE; DOPAMINE; DOPAMINERGIC NEURONS; FOLLOW-UP STUDIES; GENETIC THERAPY; GENETIC VECTORS; GTP CYCLOHYDROLASE; HUMANS; INFECTIOUS ANEMIA VIRUS, EQUINE; INJECTIONS, INTRALESIONAL; MALE; MIDDLE AGED; PARKINSON DISEASE; PUTAMEN; TRANSFECTION; TRANSGENES; TYROSINE 3-MONOOXYGENASE;

EID: 84897076939     PISSN: 01406736     EISSN: 1474547X     Source Type: Journal    
DOI: 10.1016/S0140-6736(13)61939-X     Document Type: Article

References (33)

1. de Lau LM, Breteler MM. Epidemiology of Parkinson's disease. Lancet Neurol 2006; 5: 525-35.
2. Schapira AH. Etiology and pathogenesis of Parkinson disease. Neurol Clin 2009; 27: 583-603.
3. Di Monte DA. The environment and Parkinson's disease: is the nigrostriatal system preferentially targeted by neurotoxins? Lancet Neurol 2003; 2: 531-38.
4. Hadjiconstantinou M, Neff NH. Enhancing aromatic L-amino acid decarboxylase activity: implications for L-dopa treatment in Parkinson's disease. CNS Neurosci Ther 2008; 14: 340-51.
5. Daubner SC, Le T, Wang S. Tyrosine hydroxylase and regulation of dopamine synthesis. Arch Biochem Biophys 2011; 508: 1-12.
6. Shen Y, Muramatsu SI, Ikeguchi K, et al. Triple transduction with adeno-associated virus vectors expressing tyrosine hydroxylase, aromatic-L-amino-acid decarboxylase, and GTP cyclohydrolase I for gene therapy of Parkinson's disease. Hum Gene Ther 2000; 11: 1509-19.
7. Cotzias GC, Papavasiliou PS, Gellene R. L-dopa in Parkinson's syndrome. N Engl J Med 1969; 281: 272.
8. Prashanth LK, Fox S, Meissner WG. L-dopa-induced dyskinesia-clinical presentation, genetics, and treatment. Int Rev Neurobiol 2011; 98: 31-54.
9. Olanow CW, Obeso JA, Stocchi F. Continuous dopamine-receptor treatment of Parkinson's disease: scientific rationale and clinical implications. Lancet Neurol 2006; 5: 677-87.
10. Wu K, Politis M, Piccini P. Parkinson disease and impulse control disorders: a review of clinical features, pathophysiology and management. Postgrad Med J 2009; 85: 590-96.
11. 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: 1731-35.
12. Christine CW, Starr PA, Larson PS, et al. Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology 2009; 73: 1662-69.
13. 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: 400-08.
14. 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: 1980-83.
15. 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 2007; 369: 2097-105.
16. 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: 1164-72.
17. LeWitt PA, Rezai AR, Leehy MA, et al. AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind, sham-surgery controlled, randomised trial. Lancet Neurol 2011; 10: 309-19.
18. Mitrophanous K, Yoon S, Rohll J, et al. Stable gene transfer to the nervous system using a non-primate lentiviral vector. Gene Ther 1999; 6: 1808-18.
19. Wong LF, Goodhead L, Prat C, Mitrophanous KA, Kingsman SM, Mazarakis ND. Lentivirus-mediated gene transfer to the central nervous system: therapeutic and research applications. Hum Gene Ther 2006; 17: 1-9.
20. Kordower JH, Bloch J, Ma S Y, et al. Lentiviral gene transfer to the nonhuman primate brain. Exp Neurol 1999; 160: 1-16.
21. 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: 767-73.
22. 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 2002; 22: 10302-12.
23. Mukherjee S, Thrasher AJ. Gene therapy for PIDs: progress, pitfalls and prospects. Gene 2013; 525: 174-81.
24. 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 2009; 1: 2ra4.
25. Defer GL, Widner H, Marie RM, Remy P, Levivier M. Core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT-PD). Mov Disord 1999; 14: 572-84.
26. Goetz CG, Stebbins GT, Shale HM, et al. Utility of an objective dyskinesia rating scale for Parkinson's disease: inter-and intrarater reliability assessment. Mov Disord 1994; 9: 390-94.
27. Olanow CW, Goetz CG, Kordower JH, et al. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease. Ann Neurol 2003; 54: 403-14.
28. Eggers C, Pedrosa DJ, Kahraman D, et al. Parkinson subtypes progress differently in clinical course and imaging pattern. PLoS One 2012; 7: e46813.
29. Pavese N, Evans AH, Tai YF, et al. Clinical correlates of levodopa-induced dopamine release in Parkinson disease: a PET study. Neurology 2006; 67: 1612-17.
30. Bienemann AS, Martin-Rendon E, Cosgrave AS, et al. Long-term replacement of a mutated nonfunctional CNS gene: reversal of hypothalamic diabetes insipidus using an EIAV-based lentiviral vector expressing arginine vasopressin. Mol Ther 2003; 7: 588-96.
31. Lane EL, Bjorklund A, Dunnett SB, Winkler C. Neural grafting in Parkinson's disease unraveling the mechanisms underlying graft-induced dyskinesia. Prog Brain Res 2010; 184: 295-309.
32. Freed CR, Greene PE, Breeze RE, et al. Transplantation of embryonic dopamine neurons for severe Parkinson's disease. N Engl J Med 2001; 344: 710-19.
33. Limousin P, Pollak P, Pfefen JP, Tournier-Gervason CL, Dubuis R, Perret JE. Acute administration of levodopa-benserazide and tolcapone, a COMT inhibitor, Parkinson's disease. Clin Neuropharmacol 1995; 18: 258-65.