Objective: To assess the effects of autologous implantation of fibroblasts in the internal globus pallidus of dyskinetic MPTP-lesioned monkeys upon motor behaviour and L-DOPA response.

Background: Autologous Implantation of fibroblasts (AIF) in the entopeduncular nucleus of 6-hydroxydopamine-treated rats inhibits L-dopa-induced dyskinesia (LID), and unilateral AIF to internal globus pallidus (GPi) of MPTP-induced parkinsonian macaques reduces LID on the contralateral side. We now present the effect of bilateral AIF to GPi on LID and parkinsonian behavior of MPTP-induced parkinsonian macaques.

Methods: Seventeen macaques were divided into 3 groups; control (n=5), therapeutic dose of fibroblasts as determined in previous experiment (n=6) and double this dose of fibroblasts (n=6). Parkinsonism was induced by daily MPTP administration until the animals attained a score of 7 on an accepted parkinsonism scale for MPTP-treated non-human primates. Daily treatment with Madopar (50% of the optimal dose for suppression of parkinsonism) was commenced until dyskinesia developed and became stable. Autologous fibroblasts or medium (control) were administered bilaterally to GPi.

Results: In months 1-7, both doses of fibroblasts increased the locomotor response to Madopar but enhanced dyskinesia. In months 8-9, a 25% dose of Madopar reduced parkinsonian symptoms without causing dyskinesia, and increased good on-time (GOT). In month 11, in addition to Madopar, pramipexole was administered at 100% and 33% optimal dose, which also improved parkinsonian symptomatology without causing dyskinesia and with increased GOT (Fig. 1).

Conclusions: Fibroblast implantation potentiates good effects of L-dopa and enables use of a lower, non-dyskinetic, dose.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/fibroblasts-implanted-in-internal-pallidum-of-parkinsonian-macaques-exert-l-dopa-sparing-activity/