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New experimental therapeutic approaches for Parkinson’s disease by direct DA neuronal reprogramming

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.

Field of science

  • /medical and health sciences/medical biotechnology/cells technologies/stem cells
  • /medical and health sciences/clinical medicine/transplantation
  • /medical and health sciences/basic medicine/neurology/parkinson

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
Address
Via Olgettina 60
20132 Milano
Italy
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
EU contribution
€ 1 995 267
Principal investigator
Vania Broccoli (Dr.)
Administrative Contact
Maria Rosa Pedrazzi (Dr.)

Beneficiaries (2)

OSPEDALE SAN RAFFAELE SRL
Italy
EU contribution
€ 1 995 267
Address
Via Olgettina 60
20132 Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Principal investigator
Vania Broccoli (Dr.)
Administrative Contact
Maria Rosa Pedrazzi (Dr.)
FUNDACION PARA LA INVESTIGACION MEDICA APLICADA FIMA
Spain
EU contribution
€ 420 500
Address
Avenida De Pio Xii 55
31008 Pamplona
Activity type
Research Organisations
Administrative Contact
Ana Iglesias Garcia (Mrs.)