GRAFT-IT · Enhancing Cell Replacement Therapies for Parkinson's Disease via Temporal Interference Stimulation

Parkinson’s disease (PD) is one of the most common neurological disorders, caused by the progressive loss of dopamine-producing neurons. Recent advances in stem cell biology have enabled the development of cell replacement therapies (CRTs), where dopaminergic neurons are transplanted into the brain to restore function. However, transplanted cells require years to mature and integrate into host circuits, delaying therapeutic benefits.This project introduces a novel strategy combining tissue engineering with neuromodulation to accelerate recovery. Building on recent evidence that specific electrical stimulation protocols promote neuronal maturation, the project will leverage temporal interference stimulation (TIS), a non-invasive deep brain neuromodulation technique, to enhance the functional integration of human iPSC-derived dopaminergic grafts.The GRAFT-IT (GRAft Integration via TIS) project entails three objectives: (1) identify optimal stimulation protocols for dopaminergic differentiation and function of in human neural cells, using a high-throughput in vitro platform; (2) evaluate efficacy in a preclinical model of PD using state-of-the-art neuroimaging (optogenetics-fMRI) combined with behavioral analysis, to track graft connectivity and functionality in real time; (3) validate the approach for clinical translation using GMP-compliant cell lines in collaboration with the biotech startup AzureCell, contributing to the development of a combined regulatory framework for neuromodulation and neural regeneration.By bridging deep-brain neuromodulation with regenerative medicine, the GRAFT-IT project establishes a new “electroceutical” approach for CRT in PD that aims to shorten time-to-benefit and improve therapeutic outcomes. The MSCA fellowship will allow the candidate to gain interdisciplinary skills, accelerating their academic career towards developing non-pharmacological therapies for brain regeneration with strong clinical and industrial potential.