Double transduction with GTP cyclohydrolase I and tyrosine hydroxylase is necessary for spontaneous synthesis of L-DOPA by primary fibroblasts.

摘要: Gene transfer of tyrosine hydroxylase (TH) in animal models Parkinson's disease (PD), using either genetically modified cells or recombinant virus vectors, has produced partial restoration behavioral and biochemical deficits. The limited success this approach may be related to the availability cofactor, tetrahydrobiopterin (BH4), because neither dopamine-depleted striatum nor used for gene possess a sufficient amount BH4 support TH activity. To determine role therapy, fibroblast transduced with were additionally GTP cyclohydrolase l; an enzyme critical synthesis. In contrast only TH, doubly fibroblasts spontaneously both 3, 4-dihydroxy-L-phenylalanine. examine further importance I therapy PD, vivo micro-dialysis was assess changes dopamine-denervated containing grafts fibroblasts. Only denervated striata grafted fibro-blasts possessing genes displayed restoration. However, no significant differences from controls observed apomorphine-induced rotation. This is partly attributable duration expression vivo. These between alone those indicate that rat model PD production BH4.