Objective Neurodegenerative diseases cause a significant burden on the elderly population in Europe. Parkinson’s disease (PD) affects 1.2 million people in Europe and with the increasing life expectancy this number will rise, putting more pressure on health care. Treatment of PD is only symptomatic, and therefore, there is an urgent need for more efficient therapies. Degeneration of mesencephalic DA neurons triggers the initial phases of PD, which raises the concept that cell replacement might represent a long-term restorative option for this neuropathology. Indeed, previous studies in PD patients have indicated that cell therapy has the potential to significantly sustain an enduring symptomatic relief. However, these studies suffered for lacking an ideal source of transplantable human DA neurons. Only recently the generation of induced stem cells (iPSCs) by the reprogramming of somatic cells has disclosed the possibility to generate individual specific neurons with a high therapeutic potential. We have recently developed a methodology that promotes transdifferentiation of mouse and human fibroblasts into functional induced dopaminergic neuronal (iDAN) cells. iDAN cells display sophisticated neuronal properties including pacemaking firing activity, synaptic integration, activity-dependent dopamine release and D2 functional autoreceptors. Therefore, iDAN cells offer an unprecedented cellular source with ideal features for cell therapy in PD, since they can be generated from the patients in high amounts. Here, we propose to strengthen the technology in the human setting and decipher the molecular events. Next, we will elaborate methods of in vivo reprogramming promoting neuronal transdifferentiation locally in the mouse brain. Finally, autologous transplantations of iDAN cells in parkinsonian monkeys will be attempted. Overall, this project will enhance cell reprogramming technologies with the ambition to generate a superior cellular source for transplantations in PD patients. Fields of science medical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesbasic medicineneurologyparkinsonmedical and health sciencesclinical medicinetransplantation Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-LS7 - ERC Advanced Grant - Diagnostic tools, therapies and public health Call for proposal ERC-2013-ADG See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution OSPEDALE SAN RAFFAELE SRL EU contribution € 1 995 267,00 Address VIA OLGETTINA 60 20132 Milano Italy See on map Region Nord-Ovest Lombardia Milano Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Principal investigator Vania Broccoli (Dr.) Administrative Contact Massimiliano Meoni (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all OSPEDALE SAN RAFFAELE SRL Italy EU contribution € 1 995 267,00 Address VIA OLGETTINA 60 20132 Milano See on map Region Nord-Ovest Lombardia Milano Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Principal investigator Vania Broccoli (Dr.) Administrative Contact Massimiliano Meoni (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data FUNDACION PARA LA INVESTIGACION MEDICA APLICADA FIMA Spain EU contribution € 420 500,00 Address AVENIDA DE PIO XII 55 31008 Pamplona See on map Region Noreste Comunidad Foral de Navarra Navarra Activity type Research Organisations Administrative Contact Ana Iglesias Garcia (Mrs.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
