title: Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease.
abstract: Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor with restorative effects in a wide variety of rodent and primate models of Parkinson disease, but penetration into brain tissue from either the blood or the cerebro-spinal fluid is limited. Here we delivered GDNF directly into the putamen of five Parkinson patients in a phase 1 safety trial. One catheter needed to be repositioned and there were changes in the magnetic resonance images that disappeared after lowering the concentration of GDNF. After one year, there were no serious clinical side effects, a 39% improvement in the off-medication motor sub-score of the Unified Parkinson's Disease Rating Scale (UPDRS) and a 61% improvement in the activities of daily living sub-score. Medication-induced dyskinesias were reduced by 64% and were not observed off medication during chronic GDNF delivery. Positron emission tomography (PET) scans of [(18)F]dopamine uptake showed a significant 28% increase in putamen dopamine storage after 18 months, suggesting a direct effect of GDNF on dopamine function. This study warrants careful examination of GDNF as a treatment for Parkinson disease.
authors.affiliation: Frenchay Hospital, Institute of Neurosciences, Bristol, UK. steven.gill@north-bristol.swest.nhs.uk
authors.forename: Steven S
authors.initials: SS
authors.lastname: Gill
authors.forename: Nikunj K
authors.initials: NK
authors.lastname: Patel
authors.forename: Gary R
authors.initials: GR
authors.lastname: Hotton
authors.forename: Karen
authors.initials: K
authors.lastname: O'Sullivan
authors.forename: Renée
authors.initials: R
authors.lastname: McCarter
authors.forename: Martin
authors.initials: M
authors.lastname: Bunnage
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: Clive N
authors.initials: CN
authors.lastname: Svendsen
authors.forename: Peter
authors.initials: P
authors.lastname: Heywood
mesh_terms: D004295:Dihydroxyphenylalanine / Q000378:metabolism; D005462:Fluorine Radioisotopes; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000008:administration & dosage*; D010300:Parkinson Disease / Q000188:drug therapy*; D010865:Pilot Projects; D011699:Putamen / Q000187:drug effects*; D012107:Research Design; D014055:Tomography, Emission-Computed
chemical_list: D005462:Fluorine Radioisotopes; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D004295:Dihydroxyphenylalanine