[Treatment of Parkinson's disease by cell transplantation]
Brain transplantation of neurons may reach two different targets: (1) drug delivery system: eg dopaminergic (DA) neurons in Parkinson's Disease (PD) or indirect gene therapy in Huntington's disease (HD), and (2) organotypic reconstruction: eg striatal neurons in HD. Most published reports are phase 1, pilot trials: not all patients are responders, graft is followed by a 30p.100 decrease of daily levodopa intake, with an improvement of duration and severity of defined "off" periods and a decrease of the UPDRS score measured in "off". Only one phase 2 trial is completed. A moderate improvement of motor symptoms was observed along with a decrease of daily antiparkinsonian drug intake. PET imaging with labelled fluorodopa shows typically an increase of Ki, meaning an increase of uptake in the striatum as compared to the cortex. Dyskinesias seen in some patients suggest either a lesion effect into the striatum, or indicate that the heterotopy of the grafted neurons may be partially harmful to the motor pathways. Xenografts with porcine neurons led to poor survival. More than ten years following the first published results, whereas improvement of motor symptoms and reduction or cessation of dopaminergic drugs may be observed, transplantation remains a matter of technical and ethical concerns. It remains in the field of medical research. Many questions remain unanswered, namely: the best location and size of transplantation; the amount of grafted neurons; the need and duration of immunosuppressive treatments; the best source of neurons to be tarnsplanted and the long term effect as compared to other medical or surgical treatments. Nervertheless one can be convinced that this method may be not harmful to patients and thus deserves new clinical trials aimed at giving logical and documented answers to the many questions asked above.
Cesaro
P.
P
Département de Neurosciences Médicales et Inserm U. 421, CHU Henri-Mondor, 94010 Créteil Cedex.
Greffes neuronales et maladie de Parkinson.