24 Neural Transplantation in Parkinson ’ s Disease

Parkinson’s disease (PD) is a chronic, degenerative disease characterized by a progressive loss of mesencephalic dopaminergic cells in the substantia nigra pars compacta (SNc) resulting in a loss of dopaminergic innervation to the striatum (caudate and putamen). Parkinsonian signs appear after approximately 50% of nigral cells are lost and striatal dopamine levels are reduced 80% (1). The administration of the dopamine precursor levodopa remains the cornerstone of long-term symptomatic medical management. Patients initially experience satisfactory improvement but as the disease progresses, the clinical response is frequently complicated by motor fluctuations and dyskinesias. Increased disability over time also arises in part due to nondopaminergic-responsive symptoms, including balance and cognitive dysfunction. Better treatments are needed to improve the longterm outcome of patients with PD. One approach is the transplantation of cells that might replace those that have been lost due to the disease process. In the 1970s, Bjorklund et al. demonstrated that transplanted fetal catecholaminergic and cholinergic neurons can survive, extend processes, establish synaptic connections, and enhance the release of neurotransmitters