title: Effects of intracerebral neurotrophic factor application on motor symptoms in Parkinson's disease: A systematic review and meta-analysis.
abstract: BACKGROUND
  Neurotrophic factors (NTFs) have been evaluated for neuroprotective effects in Parkinson's disease (PD). However, clinical trials examining the efficacy of intracerebral administration of NTFs on motor symptoms in PD have produced mixed results, and are thus inconclusive. The objective of this systematic review and meta-analysis was to determine the effects of intracerebral NTF application on motor symptoms in people with PD.
  
  
  METHODS
  We searched PubMed, MEDLINE, EMBASE, and Cochrane from inception through to March 31 2016 for open-label trials and randomized controlled trials (RCTs) which intracerebrally administered NTFs to PD patients, and which performed motor examination using the Unified Parkinson's Disease Rating Scale.
  
  
  RESULTS
  Eight studies with a total of 223 participants were included. Fixed effects analysis revealed that NTF treatment did not significantly reduce motor symptoms in PD patients compared to placebo controls (P = 0.98). Combining open-label and RCT data, both treatment with NTFs (P < 0.001) and treatment with placebo (P < 0.05) significantly improved motor function in PD patients when compared to predicted symptoms in untreated PD controls. Finally, random effects analysis revealed that NTF-treated PD patients were not significantly likely to improve following intracerebral NTF administration (P = 0.25).
  
  
  CONCLUSIONS
  In conclusion, intracerebral NTF administration does not improve motor symptoms in PD patients, when compared to placebo-treated controls. These findings may guide therapeutic decisions and inform future research on NTFs and their application in PD.
authors.affiliation: Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork, Cork, Ireland. Electronic address: shane.hegarty@ucc.ie.
authors.forename: Shane V
authors.initials: SV
authors.lastname: Hegarty
authors.affiliation: Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork, Cork, Ireland.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork, Cork, Ireland.
authors.forename: Gerard W
authors.initials: GW
authors.lastname: O'Keeffe
authors.affiliation: Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork, Cork, Ireland. Electronic address: a.sullivan@ucc.ie.
authors.forename: Aideen M
authors.initials: AM
authors.lastname: Sullivan
mesh_terms: D000818:Animals; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D006801:Humans; D009068:Movement / Q000187:drug effects*; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology*; D016032:Randomized Controlled Trials as Topic
chemical_list: D009414:Nerve Growth Factors; D018696:Neuroprotective Agents
keywords: Clinical trials; Neurotrophic factors; Neurotrophic therapy; Parkinson's disease; Systematic review/meta-analysis