Obiettivo The main objective of the present project is to develop cell transplantation into a clinically useful treatment for patients with Parkinson's disease.Other objectives are: to develop strategies to counteract the degeneration of dopamine neurons after transplantation in humans; to study mechanisms of action of dopaminergic grafts in parkinsonian patients; to use neural grafting as a tool to clarify the functional topography of the dopamine system in the human brain and the pathophysiology of different symptoms of Parkinson's disease; to better understand the etiology of Parkinson's disease. Currently available treatments for Parkinson's disease are insufficient, and a majority of patients become severly incapacited. A transplantation therapy would improve the quality of life and living conditions for a large number of patients. Clinical trials have demonstrated that intrastriatal grafts of fetal dopamine neurons can survive and restore function in the human Parkinsonian brain. However, the symptomatic relief is incomplete and must be improved before neural grafting should be regarded as a treatment for Parkinson's disease. We will implant fetal dopamine-rich mesencephalic tissue into the striatum in patients with idiopathic Parkinson's disease. The main goal is to increase the symptomatic relief by inducing a more complete dopaminergic reinnervation of denervated striatal sites on both sides of the brain. This will be achieved by improved procurement of the fetal tissue, by more implantation sites distributed over the entire striatum, and by promoting dopamine neuron survival and outgrowth, first, by inhibition of oxidative mechanisms and, second, by supply of neurotrophic factors. Patients will be assessed clinically before and after grafting according to the Core Assessment Program for Intracerebral Transplantations (CAPIT) and graft survival will be monitored by Positron Emission Tomography (PET) with fluorodopa as tracer. The major scientific questions are: (i) What is the maximum symptomatic relief in a parkinsonian patient after complete engraftment of the caudate and putamen bilaterally ? (ii) What is the relation between graft location and axonal outgrowth and the pattern and degree of symptomatic relief ? (iii) Can the survival of grafted dopamine neurons and the symptomatic relief in operated parkinsonian patients be improved by inhibition of oxidative mechanisms or supply of neurotrophic factors ? Campo scientifico medical and health sciencesbasic medicinephysiologypathophysiologynatural sciencesphysical sciencesastronomyplanetary sciencesplanetary geologymedical and health sciencesbasic medicineneurologyparkinsonmedical and health sciencesclinical medicinetransplantation Programma(i) FP4-BIOMED 2 - Specific research, technological development and demonstration programme in the field of biomedicine and health, 1994-1998 Argomento(i) 3.2 - Nervous system damage and repair Invito a presentare proposte Data not available Meccanismo di finanziamento CSC - Cost-sharing contracts Coordinatore Lunds Universitet Contributo UE Nessun dato Indirizzo Lund University Hospital 221 85 Lund Svezia Mostra sulla mappa Costo totale Nessun dato Partecipanti (3) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto Institute of Neurology Regno Unito Contributo UE Nessun dato Indirizzo The National Hospital Queen Square WC1N 3BG London Mostra sulla mappa Costo totale Nessun dato Philipps-Universität Marburg Germania Contributo UE Nessun dato Indirizzo 8,Rudolf-Bultmann-Str. 35033 Marburg Mostra sulla mappa Costo totale Nessun dato Royal Postgraduate Medical School Regno Unito Contributo UE Nessun dato Indirizzo 150,Du Cane Road W12 ONN London Mostra sulla mappa Costo totale Nessun dato