Foetal mesencephalic tissue has been implanted in the striatum of patients with the juvenile form of Parkinson's disease and has been shown to develop functional axons; this has enabled the dose of L-dopa to be reduced. Both imaging and pharmacological studies have now shown that functional dopaminergic neurons can develop in the brain of the patient following tissue transplantation. However, a major ethical objection has been raised to such transplants as six to seven foetal brains are required to obtain sufficient tissue. In addition, only about 20% of neurons survive transplantation. The ethical problem may be overcome by using brain transplants from domestic animals such as pigs. Such xenotransplants have been shown to survive in the human brain but the main problem with the extensive use of such transplants is the possible spread of viruses and prion infections.
Other techniques which may overcome the need for foetal tissue or xenotransplants include the implantation of mesencephalic dopaminergic neurons grown in cell culture or, alternatively, the use of stem cells of human origin.
There is evidence that trophic factors, which are essential for the development of neurons and their maintenance in the adult brain, could play a role in delaying the degenerative changes in the brain of a patient with Parkinson's disease. Such trophic factors include the epidermal growth factor, basic fibroblast growth factor, brain-derived neurotrophic factor and the glia-derived neurotrophic factor. These factors have been shown to enhance the survival and growth of dopaminergic neurons in cell culture. The glia-derived neurotrophic factor appears to be particularly specific in stimulating the growth of dopaminergic neurons. It is now possible to add the appropriate factors to fetal dopaminergic cells prior to their transplantation to ensure their long-term viability and differentiation.
In CONCLUSION, the last 30 years have witnessed many important advances in our understanding of Parkinson's disease. Based on this understanding drugs have been developed that have led to a significant reduction in the mortality of patients with the disease. However, despite these advances there is no evidence that the drugs available prevent the progression of the disease. Perhaps the application of growth factors will provide the clinician with the means whereby this can be achieved.
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