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 ?
Funding SchemeCSC - Cost-sharing contracts
WC1N 3BG London
W12 ONN London