Neurodegenerative disorders (ND) are expected to surpass cancer as the most common group of medical conditions by 2040. A prominent example of ND is Parkinson’s disease (PD), a medical condition that already affects 6.5 million people worldwide, a number expected to more than double by 2030. Curative treatment of PD and ND is considered as one of the great challenges to medical science and alternative medical routes needs to be devised since current therapies are not yet satisfactory.
Among these, cell replacement therapy (CT) is considered the most promising approach. It consists of transplanting cells into the brain to replace degenerating neurons. The transplantation of DA neurons derived from developing embryos into PD patients has already been tested in clinical trials. Despite promising results, practical, medical and ethical concerns restrict the use of human fetal tissue. With the advent of stem cell reprogramming technologies, induced pluripotent stem cells (iPS) generated from the patient’s own cells have thus emerged as a promising alternative source of DA. Yet, there are still serious obstacles for replacement therapy using iPS-derived neurons. Furthermore, precursor neurons transplanted into the brain region where neuronal cell bodies degenerate have to grow long distances to achieve re-innervation and functional repair.
The MAGNEURON project aims at developing a novel technology for magnetic actuation of cellular functions to treat ND. The innovative concept of our technology is to remote-control cellular signaling pathways by means of biofunctionalized magnetic nanoparticles (bMNPs) engineered to function as intracellular signaling nanoplatforms. Once delivered into the cytoplasm of target cells, bMNPs can activate signaling pathways in response to external magnetic fields in either a spatial and/or a temporal mode.
With this novel technology, our long-term goal is to fundamentally advance cell therapies and regenerative medicine in the brain by remote-controlling the differentiation and oriented growth of transplanted cells. In the context of PD, we will focus on the control of signaling pathways known to promote the survival, differentiation and growth of transplanted DA precursor neurons. The key objectives of our project are: (i) the development of the chemical, biochemical and physical tools for the magnetic control of signaling in stem cells and neuronal cells, (ii) the demonstration of magnetic actuation of differentiation of DA precursor neurons and guidance of DA neurites in single-cell in vitro assays and (iii) the application of the technology with cells transplanted into organotypic brain slices and rodents.
