Continuous Low-Level Glial Cell Line-Derived Neurotrophic Factor Delivery Using Recombinant Adeno-Associated Viral Vectors Provides Neuroprotection and Induces Behavioral Recovery in a Primate Model of Parkinson's Disease

• DOI: 10.1523/jneurosci.4421-04.2005
• Publication Date: 2005-01-27T03:05:19Z
• Authors: Andisheh Eslamboli; Biljana Georgievska; Rosalind M. Ridley; Harry F. Baker; Nicholas Muzyczka; Corinna Burger; Ronald J. Mandel; Lucy Annett; Deniz Kirik
• Keywords: Male; Appetitive Behavior; Dopamine; Genetic Vectors; Green Fluorescent Proteins; Callithrix; Parkinson Disease; Genetic Therapy; Dependovirus; Motor Activity; Choice Behavior; Nerve Regeneration; Neostriatum; Disease Models, Animal; 03 medical and health sciences; 0302 clinical medicine; Animals; Female; Glial Cell Line-Derived Neurotrophic Factor; Nerve Growth Factors; Parkinson Disease, Secondary; Oxidopamine

The therapeutic potential of glial cell line-derived neurotrophic factor (GDNF) for Parkinson's disease is likely to depend on sustained delivery the appropriate amount target areas. Recombinant adeno-associated viral vectors (rAAVs) expressing GDNF may be a suitable system this purpose. aim study was define level that does not affect function normal dopamine (DA) neurons but provide anatomical and behavioral protection against an intrastriatal 6-hydroxydopamine (6-OHDA) lesion in common marmoset. We found unilateral injection rAAV resulting expression high levels (14 ng/mg tissue) striatum induced substantial bilateral increase tyrosine hydroxylase protein activity as well DA turnover. Expression low (0.04 tissue), other hand, produced only minimal effects synthesis injected side. In addition, provided ∼85% nigral their projections 6-OHDA-lesioned hemisphere. Furthermore, accompanied by complete attenuation sensorimotor neglect, head position bias, amphetamine-induced rotation. conclude when delivered continuously, (approximately threefold above baseline) sufficient optimal functional outcome.