title: Safety/feasibility of targeting the substantia nigra with AAV2-neurturin in Parkinson patients.
abstract: OBJECTIVE
  In an effort to account for deficiencies in axonal transport that limit the effectiveness of neurotrophic factors, this study tested the safety and feasibility, in moderately advanced Parkinson disease (PD), of bilaterally administering the gene therapy vector AAV2-neurturin (CERE-120) to the putamen plus substantia nigra (SN, a relatively small structure deep within the midbrain, in proximity to critical neuronal and vascular structures).
  
  
  METHODS
  After planning and minimizing risks of stereotactically targeting the SN, an open-label, dose-escalation safety trial was initiated in 6 subjects with PD who received bilateral stereotactic injections of CERE-120 into the SN and putamen.
  
  
  RESULTS
  Two-year safety data for all subjects suggest the procedures were well-tolerated, with no serious adverse events. All adverse events and complications were expected for patients with PD undergoing stereotactic brain surgery.
  
  
  CONCLUSIONS
  Bilateral stereotactic administration of CERE-120 to the SN plus putamen in PD is feasible and this evaluation provides initial empirical support that it is safe and well-tolerated.
  
  
  METHODS
  This study provides Class IV evidence that bilateral neurturin gene delivery (CERE-120) to the SN plus putamen in patients with moderately advanced PD is feasible and safe.
authors.affiliation: Ceregene, Inc., San Diego, CA, USA. rtbartus@ceregene.com
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Bartus
authors.forename: Tiffany L
authors.initials: TL
authors.lastname: Baumann
authors.forename: Joao
authors.initials: J
authors.lastname: Siffert
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Herzog
authors.forename: Ron
authors.initials: R
authors.lastname: Alterman
authors.forename: Nicholas
authors.initials: N
authors.lastname: Boulis
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Turner
authors.forename: Mark
authors.initials: M
authors.lastname: Stacy
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
authors.forename: Andres M
authors.initials: AM
authors.lastname: Lozano
authors.forename: C Warren
authors.initials: CW
authors.lastname: Olanow
mesh_terms: D000229:Dependovirus / Q000235:genetics*; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D018014:Gene Transfer Techniques / Q000009:adverse effects; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008297:Male; D008845:Microinjections / Q000379:methods; D008875:Middle Aged; D051101:Neurturin / Q000235:genetics*; D010300:Parkinson Disease / Q000628:therapy*; D013238:Stereotaxic Techniques; D013378:Substantia Nigra / Q000502:physiology*; D016896:Treatment Outcome
chemical_list: C495053:NRTN protein, human; D051101:Neurturin