title: Recombinant adeno-associated viral vector (rAAV) delivery of GDNF provides protection against 6-OHDA lesion in the common marmoset monkey (Callithrix jacchus).
abstract: Glial cell line-derived neurotrophic factor (GDNF) has shown potential as a treatment for Parkinson's disease. Recombinant adeno-associated viral vectors expressing the GDNF protein (rAAV-GDNF) have been used in rodent models of Parkinson's disease to promote functional regeneration after 6-OHDA lesions of the nigrostriatal system. The goal of the present study was to assess the anatomical and functional efficacy of rAAV-GDNF in the common marmoset monkey (Callithrix jacchus). rAAV-GDNF was injected into the striatum and substantia nigra 4 weeks prior to a unilateral 6-OHDA lesion of the nigrostriatal bundle. Forty percent of the dopamine cells in the lesioned substantia nigra of the rAAV-GDNF-treated monkeys survived, compared with 21% in the untreated monkeys. Fine dopaminergic fibres were observed microscopically in the injected striatum of some rAAV-GDNF-treated monkeys, suggesting that rAAV-GDNF treatment may have prevented, at least in part, the loss of dopaminergic innervation of the striatum. Protection of dopamine cells and striatal fibre innervation was associated with amelioration of the lesion-induced behavioural deficits. rAAV-GDNF-treated monkeys showed partial or complete protection not only in the amphetamine and apomorphine rotation but also in head position and the parkinsonian disability rating scale. Therefore, our study provides evidence for the behavioural and anatomical efficacy of GDNF delivered via an rAAV vector as a possible treatment for Parkinson's disease.
authors.affiliation: Department of Experimental Psychology, Downing Street, University of Cambridge, CB2 3EB, Cambridge, UK. ae228@hermes.cam.ac.uk
authors.forename: Andisheh
authors.initials: A
authors.lastname: Eslamboli
authors.forename: Rosalyn M
authors.initials: RM
authors.lastname: Cummings
authors.forename: Rosalind M
authors.initials: RM
authors.lastname: Ridley
authors.forename: Harry F
authors.initials: HF
authors.lastname: Baker
authors.forename: Nicholas
authors.initials: N
authors.lastname: Muzyczka
authors.forename: Corinna
authors.initials: C
authors.lastname: Burger
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Mandel
authors.forename: Deniz
authors.initials: D
authors.lastname: Kirik
authors.forename: Lucy E
authors.initials: LE
authors.lastname: Annett
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002144:Callithrix; D002452:Cell Count; D005822:Genetic Vectors; D051100:Glial Cell Line-Derived Neurotrophic Factor; D019416:Head Movements / Q000502:physiology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D026901:Membrane Transport Proteins; D009412:Nerve Fibers / Q000473:pathology; D009414:Nerve Growth Factors / Q000235:genetics* / Q000502:physiology*; D009479:Neuropeptides; D016627:Oxidopamine / Q000633:toxicity*; D012399:Rotation; D013239:Stereotyped Behavior / Q000502:physiology; D013378:Substantia Nigra / Q000473:pathology; D013565:Sympatholytics / Q000633:toxicity*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D050492:Vesicular Biogenic Amine Transport Proteins
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009414:Nerve Growth Factors; D009479:Neuropeptides; D013565:Sympatholytics; D050492:Vesicular Biogenic Amine Transport Proteins; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase