Neuroprotective effects of encapsulated CNTF-producing cells in a rodent model of Huntington's disease are dependent on the proximity of the implant to the lesioned striatum.
Huntington's disease (HD) is a devastating genetic disorder with no effective treatments for preventing or lessening the underlying neuronal degeneration. Intracerebral delivery of CNTF in animal models of HD has shown considerable promise as a means of protecting striatal neurons that would otherwise be destined to die. The present study examines whether the neuroprotective effects of CNTF require that the delivery be immediately proximal to the lesion site or whether protective effects can be exerted when the delivery site is more distal to the site of injury. Encapsulated CNTF-producing cells were implanted into the lateral ventricle either ipsilateral or contralateral to an intrastriatal quinolinic acid (QA) injection. A robust neuroprotective effect was observed only in those animals receiving CNTF implants ipsilateral to the QA injection. In these animals, the loss of striatal ChAT and GAD activity as well as the behavioral impairments that resulted from QA were completely prevented. In contrast, no neurochemical or behavioral benefits were produced by implants of CNTF-producing cells in the contralateral ventricle. These data continue to support the use of cellular delivery of CNTF for HD but caution that delivery directly to the striatum may be needed if any clinical benefits are to be seen.
Emerich
Dwaine F
DF
CytoTherapeutics, Inc., Providence, RI, USA. ed3fjm@aol.com
Winn
Shelley R
SR
D000818:Animals; D001522:Behavior, Animal; D016380:Brain Tissue Transplantation / Q000379:methods*; D002460:Cell Line; D017690:Cell Transplantation / Q000379:methods*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism / Q000502:physiology*; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods; D006816:Huntington Disease / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017378:Quinolinic Acid / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D020934:Ciliary Neurotrophic Factor; D018696:Neuroprotective Agents; D002795:Choline O-Acetyltransferase; D017378:Quinolinic Acid