Understanding graft-induced dyskinesia

The transplantation of dopaminergic cells for the treatment of symptoms of Parkinson’s disease has several hurdles to overcome before it can be considered a successful therapeutic approach. One issue is the development of abnormal involuntary movements in the absence of L-3,4-dihydroxyphenylalanine following the transplantation of fetal ventral mesencephalon identified in three different clinical trials. Hypotheses as to the cause of these movements include: the composition of the graft, size of the graft, L-3,4-dihydroxyphenylalanine exposure and L-3,4-dihydroxyphenylalanine-induced dyskinesia prior to transplantation and inflammatory responses in and around the graft. We evaluate the clinical evidence supporting these hypotheses and the preclinical models upon which experiments are being based to resolve them.