Neural progenitors for Parkinson's treatment
Parkinson's disease (PD), affecting over one million people in the EU, is characterised by progressive loss of mobility, tremor and speech difficulties. The result of loss of dopamine-producing neurons in the substantia nigra region of the mesencephalon (mid-brain), PD is a progressive condition that carries a large social and economic cost. Possible therapies include pharmaceuticals and surgery. One successful surgical procedure uses foetal grafts but this raises ethical and practical issues. The EU project DANCE therefore investigated the option of human neural stem cell surgery. The overall objective was to produce a human dopaminergic cell line that would be transplantable into PD patients. Project partners at Lund University in Sweden aimed to develop a method to specifically identify mesencephalic dopaminergic (mesDA) neuron precursors. A potential key to the isolation of mesDA neuron precursors was the gene Neurogenin2, Ngn2, previously implicated in neurogenesis induction. Knock-in Ngn2-GFP (Green fluorescent protein) mice were used as a reporter strain to study the action of Ngn2. Using the fluorescence of activated genes, cells were selected by FACS (Fluorescene-activated cell sorting). Those with activated Ngn2 were capable of generating mature mesDA neurons, both in vitro and in vivo. Specificity was high on the agenda of the scientists. The Ngn2-GFP population which expressed the gene gave rise to mesDA neurons only and not those neuron precursors producing other neurotransmitters such as serotonin. This pointed to Ngn2 being selectively involved in the generation of mesDA in the ventral mesencephalon where two major dopamine cell types are found. The results of this research have been published in the journal Experimental Neurology. It would appear that proneural gene Ngn2 can confidently be used as a marker gene for the selection of early mesDA neuron precursors. As such, the gene could be an integral part of a novel therapy for Parkinson's disease.
