Grafts in the treatment of Parkinson's disease: animal models.
Long-term treatment of parkinsonian patients with L-DOPA leads to a loss of efficacy over time and the appearance of important side effects such as dyskinesias. Grafts of chromaffin cells of the adrenal medulla or fetal ventral mesencephalic neurons bring behavioral improvement in animal models of Parkinson's disease. These improvements are likely to be related to the secretion of dopamine by the grafted cells and/or to the reinnervation of the host tissue. In addition, a leak in the blood-brain barrier may allow peripheral catecholamines to gain access to the brain. Lack of clear effects of grafts in parkinsonian patients may be due to their poor survival in the human brain. Improvement of grafting techniques as well as the addition of neurotrophic factors to grafts may help increase their survival and improve behavioral effects. Recently, genetic techniques have allowed the creation of genetically modified cell lines which can produce L-DOPA and these cells may be grafted in the brain. Interestingly, these cell lines may be encapsulated in permselective membranes which can protect them from immunological rejection and avoid the uncontrolled cell growth of these mitotically active cells. Grafting techniques seem to be an interesting alternative to treat parkinsonian patients. Improvement of grafting procedures may help increase survival of grafts and thus enhance behavioral improvements. Moreover, genetic modification of well-known tumor cell lines or patient's own cells such as astrocytes may help avoid the low availability as well as ethical and immunological problems linked to the use of fetal human tissue.
School of Pharmacy, Laval University, Quebec, Canada.
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C
Gagnon
P J
PJ
Bédard
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T
Di Paolo
D000313:Adrenal Medulla / Q000166:cytology* / Q000637:transplantation*; D000818:Animals; D004195:Disease Models, Animal; D016332:Fetal Tissue Transplantation; D005333:Fetus / Q000166:cytology; D008636:Mesencephalon / Q000196:embryology*; D010300:Parkinson Disease / Q000601:surgery*