title: Encapsulated cell-based biodelivery of meteorin is neuroprotective in the quinolinic acid rat model of neurodegenerative disease.
abstract: OBJECTIVE
  Encapsulated cell (EC) biodelivery is a promising, clinically relevant technology platform to safely target the delivery of therapeutic proteins to the central nervous system. The purpose of this study was to evaluate EC biodelivery of the novel neurotrophic factor, Meteorin, to the striatum of rats and to investigate its neuroprotective effects against quinolinic acid (QA)-induced excitotoxicity.
  
  
  METHODS
  Meteorin-producing ARPE-19 cells were loaded into EC biodelivery devices and implanted into the striatum of rats. Two weeks after implantation, QA was injected into the ipsilateral striatum followed by assessment of neurological performance two and four weeks after QA administration.
  
  
  RESULTS
  Implant-delivered Meteorin effectively protected against QA-induced toxicity, as manifested by both near-normal neurological performance and reduction of brain cell death. Morphological analysis of the Meteorin-treated brains showed a markedly reduced striatal lesion size. The EC biodelivery devices produced stable or even increasing levels of Meteorin throughout the study over 6 weeks.
  
  
  CONCLUSIONS
  Stereotactically implanted EC biodelivery devices releasing Meteorin could offer a feasible strategy in the treatment of neurological diseases with an excitotoxic component such as Huntington's disease. In a broader sense, the EC biodelivery technology is a promising therapeutic protein delivery platform for the treatment of a wide range of diseases of the central nervous system.
authors.affiliation: NsGene A/S, Ballerup, Denmark. jt@nsgene.com
authors.forename: Jens
authors.initials: J
authors.lastname: Tornøe
authors.forename: Malene
authors.initials: M
authors.lastname: Torp
authors.forename: Jesper Roland
authors.initials: JR
authors.lastname: Jørgensen
authors.forename: Dwaine F
authors.initials: DF
authors.lastname: Emerich
authors.forename: Chris
authors.initials: C
authors.lastname: Thanos
authors.forename: Briannan
authors.initials: B
authors.lastname: Bintz
authors.forename: Lone
authors.initials: L
authors.lastname: Fjord-Larsen
authors.forename: Lars U
authors.initials: LU
authors.lastname: Wahlberg
mesh_terms: D020341:Absorbable Implants / Q000592:standards*; D000818:Animals; D016380:Brain Tissue Transplantation / Q000379:methods; D002214:Capsules / Q000008:administration & dosage; D002460:Cell Line; D019610:Cytoprotection / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D006816:Huntington Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000378:metabolism; D011804:Quinolines / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002214:Capsules; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011804:Quinolines; C502098:meteorin protein, mouse; C037219:quinoline