title: Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease.
abstract: OBJECTIVE
  Glial cell line-derived neurotrophic factor (GDNF) exerts potent trophic influence on midbrain dopaminergic neurons. This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open-label trial using intraputamenal (Ipu) infusion of recombinant human GDNF (liatermin).
  
  
  METHODS
  Thirty-four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15 microg/putamen/day or placebo. The primary end point was the change in Unified Parkinson Disease Rating Scale (UPDRS) motor score in the practically defined off condition at 6 months. Secondary end points included other UPDRS scores, motor tests, dyskinesia ratings, patient diaries, and (18)F-dopa uptake.
  
  
  RESULTS
  At 6 months, mean percentage changes in "off" UPDRS motor score were -10.0% and -4.5% in the liatermin and placebo groups, respectively. This treatment difference was not significant (95% confidence interval, -23.0 to 12.0, p = 0.53). Secondary end point results were similar between the groups. A 32.5% treatment difference favoring liatermin in mean (18)F-dopa influx constant (p = 0.019) was observed. Serious, device-related adverse events required surgical repositioning of catheters in two patients and removal of devices in another. Neutralizing antiliatermin antibodies were detected in three patients (one on-study and two in the open-label extension).
  
  
  CONCLUSIONS
  Liatermin did not confer the predetermined level of clinical benefit to patients with PD despite increased (18)F-dopa uptake. It is uncertain whether technical differences between this trial and positive open-label studies contributed in any way this negative outcome.
authors.affiliation: Toronto Western Hospital, University of Toronto, Ontario, Canada. lang@uhnres.utoronto.ca
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
authors.forename: Steven
authors.initials: S
authors.lastname: Gill
authors.forename: Nik K
authors.initials: NK
authors.lastname: Patel
authors.forename: Andres
authors.initials: A
authors.lastname: Lozano
authors.forename: John G
authors.initials: JG
authors.lastname: Nutt
authors.forename: Richard
authors.initials: R
authors.lastname: Penn
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: Gary
authors.initials: G
authors.lastname: Hotton
authors.forename: Elena
authors.initials: E
authors.lastname: Moro
authors.forename: Peter
authors.initials: P
authors.lastname: Heywood
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brodsky
authors.forename: Kim
authors.initials: K
authors.lastname: Burchiel
authors.forename: Patrick
authors.initials: P
authors.lastname: Kelly
authors.forename: Arif
authors.initials: A
authors.lastname: Dalvi
authors.forename: Burton
authors.initials: B
authors.lastname: Scott
authors.forename: Mark
authors.initials: M
authors.lastname: Stacy
authors.forename: Dennis
authors.initials: D
authors.lastname: Turner
authors.forename: V G Frederich
authors.initials: VG
authors.lastname: Wooten
authors.forename: William J
authors.initials: WJ
authors.lastname: Elias
authors.forename: Edward R
authors.initials: ER
authors.lastname: Laws
authors.forename: Vijay
authors.initials: V
authors.lastname: Dhawan
authors.forename: A Jon
authors.initials: AJ
authors.lastname: Stoessl
authors.forename: James
authors.initials: J
authors.lastname: Matcham
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Coffey
authors.forename: Michael
authors.initials: M
authors.lastname: Traub
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D004341:Drug Evaluation; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D011699:Putamen / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D011994:Recombinant Proteins; D004295:Dihydroxyphenylalanine