title: Neurotrophic factors as a therapeutic target for Parkinson's disease.
abstract: BACKGROUND
  The search for therapeutic agents that might alter the disease course in Parkinson's disease (PD) is ongoing. One area of particular interest involves neurotrophic factors (NTFs), with those of the glial cell line-derived neurotrophic factor (GDNF) family showing greatest promise. The safety and efficacy of these therapies has recently come into question. Furthermore, many of the key questions pertaining to such therapies, such as the optimal method of delivery, timing of treatment and selection of patients most likely to benefit, remain unanswered.
  
  
  OBJECTIVE
  In this review we sought to evaluate the therapeutic potential of NTFs in the treatment of PD. We appraised the evidence provided by both in vitro and in vivo work before proceeding to a critical assessment of the relevant clinical trial data.
  
  
  METHODS
  Relevant literature was identified using a PubMed search of articles published up to October 2007. Search terms included: 'Parkinson's disease', 'Neurotrophic factors', 'BDNF' (Brain-derived neurotrophic factor), 'GDNF' and 'Neurturin'. Original articles were reviewed, and relevant citations from these articles were also appraised.
  
  
  CONCLUSIONS
  NTF therapy has potential in the treatment of nigrostriatal dysfunction in PD but numerous methodological and safety issues will need to be addressed before this approach can be widely adopted. Furthermore PD is now recognized as being more than a pure motor disorder, and one in which neuronal loss is not just confined to the dopaminergic nigrostriatal system. Non-motor symptomatology in PD is unlikely to benefit from therapies that target only the nigrostriatal system, and this must inform our thinking as to the maximal achievable benefit that NTFs are ever likely to provide.
authors.affiliation: University of Cambridge, Cambridge Centre for Brain Repair, Department of Clinical Neuroscience, UK. jre24@cam.ac.uk
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Evans
authors.forename: Roger A
authors.initials: RA
authors.lastname: Barker
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009414:Nerve Growth Factors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy*
chemical_list: D000978:Antiparkinson Agents; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors