IMPLANTS OF ENCAPSULATED HUMAN CNTF-PRODUCING FIBROBLASTS PREVENT BEHAVIORAL DEFICITS AND STRIATAL DEGENERATION IN A RODENT MODEL OF HUNTINGTONS-DISEASE

Delivery of neurotrophic molecules to the CNS has gained considerable attention as a potential treatment strategy for neurological disorders . in the present study, a DHFR-based expression vector containing the human ciliary neurotrophic factor (hCNTF) was transfected into a baby hamster kidney fibroblast cell line (BHK). Using a polymeric device, e ncapsulated BHK-control cells and those secreting hCNTF (BHK-hCNTF) we re transplanted unilaterally into the rat lateral ventricle. Twelve da ys later, the same animals received unilateral injections of quinolini c acid (QA; 225 nmol) into the ipsilateral striatum. After surgery, an imals were behaviorally tested for apomorphine-induced rotation behavi or and for skilled forelimb function using the staircase test. Rats re ceiving BHK-hCNTF cells rotated significantly less than animals receiv ing BHK-control cells. No behavioral effects of hCNTF were observed on the staircase test. Nissl-stained sections demonstrated that BHK-hCNT F cells significantly reduced the extent of striatal damage produced b y QA. Quantitative analysis of striatal neurons further demonstrated t hat both choline acetyltransferase- and GAD-immunoreactive neurons wer e protected by BHK-hCNTF implants. In contrast, a similar loss of NADP H-diaphorase-positive cells was observed in the striatum of both impla nt groups. Analysis of retrieved capsules revealed numerous viable and mitotically active BHK cells that continued to secrete hCNTF. These r esults support the concepts that implants of polymer-encapsulated hCNT F-releasing cells can be used to protect striatal neurons from excitot oxic damage and that this strategy may ultimately prove relevant for t he treatment of Huntington's disease.