Researchers develop new technology to generate dopamine neurons by conversion of human skin fibroblasts

A study of the San Raffaele Hospital in Milan has developed a new technology to generate dopamine neurons by conversion of human skin fibroblasts. The new technique is based on the activation of only 3 genes (Mash1, Nurr1, Lmx1a) in fibroblasts that allow their conversion into dopamine neurons. These neurons, called IDA-induced dopaminergic neurons (DA neurons induced), have functional capabilities similar to those of neurons in the brain. In fact, the iDA neurons show spontaneous electrical activity, form synaptic contacts and release dopamine, the neurotransmitter that mediates the main function normally in their brains. This technique represents a further development of genetic reprogramming technology proposed by prof. S Yamanaka of Kyoto for the generation of reprogrammed stem cells (iPS), but unlike the latter, the new technique does not involve the generation of stem cells: it is a direct conversion of fibroblasts into dopaminergic neurons. This protocol avoids the generation of cancer stem cells and therefore potentially can be immediately used in preclinical studies of the disease. The work, published in the prestigious scientific journal Nature , was led by Dr Vania Broccoli, director of Stem Cells and Neurogenesis in the Unity of ' Scientific Institute San Raffaele in Milan in collaboration with research groups of Dr Alexander Dityatev, Raul Gainetdinov, Stefano Taverna the Italian Institute of Technology (IIT) in Genoa and Dr Stefano Gustincich SISSA of Trieste. The study has also benefited from the collaboration of Professor Gianni Pezzoli, Parkinson Institute Clinical Director of the Institute of Improvement (ICP), Milan and Fondazione Grigioni for Parkinson's disease. Parkinson's disease affects 200,000 people in Italy alone . The initial symptoms cause motor disturbances of various kinds caused by the degeneration of midbrain dopaminergic neurons of the substantia nigra and the loss of dopamine, the neurotransmitter they produce. The ability to transplant new neurons that can replace those lost during the actual disease is a therapeutic option, but requires a source of homologous neurons suitable for transplantation. Until now the only source of neurons used was that from fetal tissues, but the limited availability and their degree of heterogeneity have limited therapeutic success and also creating serious concerns for public ethics. Dr Vania Broccoli, coordinator of the study says: “The iDA neurons have important advantages such as can be generated by the patient himself, in a reproducible way, in a relatively short time and without any risk of cancer. However, only future studies being planned directly in animal models of Parkinson's disease will verify if the neurons can become a source iDA suitable for this use in the clinic.” The research was funded by: Ministry of Health, Italian Institute of Technology (IIT), Grigioni Foundation for Parkinson's disease and Cariplo.