Dose-dependent neurochemical and functional protection afforded by encapsulated CNTF-producing cells.
Intracerebral delivery of hCNTF has shown considerable neuroprotective potential in animal models of Huntington's disease (HD). The present study describes the relationship between a range of hCNTF doses and the resulting behavioral and neurochemical (striatal ChAT and GAD activity) protection in a rodent model of HD. Encapsulated BHK delivering a range of hCNTF doses were implanted into the lateral ventricle ipsilateral to an intrastriatal quinolinic acid (QA) injection. Results demonstrated a dose-dependent effect of hCNTF with complete, partial, and no observable neuroprotection occurring with preimplant doses of hCNTF of 30.8, 8.6, and 0.8-2.1 ng hCNTF/24 h, respectively. These data continue to support the use of cellular delivery of hCNTF for HD and will facilitate the optimization of this approach in the clinical situation.
Emerich
Dwaine F
DF
LCT BioPharma, Inc, Glocester, RI 02857, USA. ed3fjm@aol.com
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D017690:Cell Transplantation / Q000379:methods*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D020934:Ciliary Neurotrophic Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000503:physiopathology / Q000601:surgery; D006224:Cricetinae; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism / Q000637:transplantation*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006816:Huntington Disease / Q000628:therapy*; D008297:Male; D008567:Membranes, Artificial; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D014183:Transplantation, Heterologous / Q000379:methods; D016896:Treatment Outcome
D020934:Ciliary Neurotrophic Factor; D008567:Membranes, Artificial; D018696:Neuroprotective Agents; D011993:Recombinant Fusion Proteins; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase