MAGNEURON · Hijacking cell signalling pathways with magnetic nanoactuators for remote-controlled stem cell therapies of neurodegenerative disorders

Neurodegenerative diseases, such as Parkinson’s disease, are a major public health issue given the aging population inEurope and beyond. While curative pharmacological treatment of these diseases is not in sight, cell replacement therapies(CTs) are considered very promising, in particular with the advent of stem-cell reprogramming technologies. However, afundamental challenge in the medical application of CTs in the brain of patients lies in the lack of control of cell behaviour atthe site of transplantation, and particularly their differentiation and oriented growth. The aim of this project is to introduce afundamentally new concept for remote control of cellular functions by means of magnetic manipulation. The technology isbased on magnetic nanoparticles functionalized with proteins involved in cellular signalling cascades. Thesebiofunctionalized MNPs (bMNPs) will be delivered into target cells, where they act as intracellular signalling platformsactivatable in a spatially and temporally controlled manner by external magnetic fields. The project will focus on engineeringthese tools for the control of neuronal cell programming and fibre outgrowth by hijacking Wnt and neurotrophin signalling,respectively, with the ulti-mate objective of advancing cell replacement therapies for PD using dopaminergic precursorneurons.To achieve this ambitious goal, we have gathered an interdisciplinary consortium interfacing scientists having cutting-edgeknow-how in bMNP engineering, surface functionalization and cellular nanobiophysics with renowned experts in neuronalcell differentiation, stem-cell reprogramming and regenerative (nano-)medicine. By exploiting this complementary expertise,a novel, versatile technology for magnetic control of intracellular signalling is envis-aged, which will be a breakthrough forremote actuation of cellular functions and its successful implementation in CTs for neurodegenerative diseases and injurieswithin the following decade.