title: Non-viral gene delivery of the GDNF, either alone or fused to the C-fragment of tetanus toxin protein, prolongs survival in a mouse ALS model.
abstract: OBJECTIVE
  Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease with no effective therapy. Glial-cell line derived neurotrophic factor (GDNF) has been translated to clinical trials for treatment of ALS and its selective delivery to the motoneurons could improve its therapeutic abilities.
  
  
  METHODS
  To test this idea, we genetically fused GDNF to the C-fragment of tetanus toxin (TTC), a peptide able to specifically deliver molecules to motoneurons.
  
  
  RESULTS
  Single intramuscular administration of naked-DNA encoding GDNF or GDNF-TTC significantly delayed the onset of symptoms and functional deficits into the SODG93A mouse model of ALS, prolonging their lifespan.
  
  
  CONCLUSIONS
  We have demonstrated a neuroprotective effect of GDNF-TTC as shown by the activation of survival pathways and inhibition of apoptotic proteins, such as Akt phosphorylation, or reduced caspase-3 activation respectively. However, the GDNF fusion with TTC did not improve the therapeutic effects when compared to GDNF alone.
authors: Laboratorio de Genética Bioquímica, Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain.
authors: María
authors: M
authors: Moreno-Igoa
authors: Ana Cristina
authors: AC
authors: Calvo
authors: Jesús
authors: J
authors: Ciriza
authors: María Jesús
authors: MJ
authors: Muñoz
authors: Pilar
authors: P
authors: Zaragoza
authors: Rosario
authors: R
authors: Osta
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000628:therapy*; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics; D013744:Tetanus Toxin / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: C522217:CDNF protein, human; D009414:Nerve Growth Factors; D010446:Peptide Fragments; D013744:Tetanus Toxin; C040635:tetanus toxin fragment C; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3