A synaptic mechanogenetic technology to repair brain connectivity

Miriamo a sviluppare una tecnologia meccanogenetica per controllare la connettività funzionale dei circuiti neurali e mostrare come possa essere utilizzata a scopi terapeutici per disturbi cerebrali.

We aim to develop a mechanogenetic technology to control functional connectivity of neural circuits, and show how it can be harnessed for therapeutic purposes in treatment-resistant brain disorders. Mechanogenetics is an emerging field of health science that attempts to regulate neural networks by combining the advantages of optogenetics with those of magnetomechanical stimulations; like optogenetics, it relies on targeted actuators to achieve circuit specificity, while exploiting magnetic fields to remotely stimulate the brain. Yet, despite solid theoretical foundations and encouraging experimental results, we are to date unable to repair a dysfunctional brain using mechanogenetics due to technological barriers in spatial resolution and in vivo implementation. We propose an innovative solution based on biocompatible functionalized magnetic nanoparticles and bioengineered synaptic mechanosensors that synergistically target specific synaptic connections to repair dysfunctional brain circuits in response to focused magnetic fields delivered via high-permeability transcranial magnetic stimulators. By hijacking the signaling pathways of synaptic mechanosensors, we aim to promote a lasting reprogramming of neural circuits. We will bring the synaptic mechanogenetic toolkit through biological testing in mouse models of high-prevalence brain disorders (intellectual disability, Alzheimer’s disease and stroke). To achieve this ambitious goal, we have gathered an interdisciplinary consortium going from material scientists and electronic experts to physiologists and clinicians. Our approach, based on magnetic fields that penetrate brain tissue unimpeded, is predicted to go beyond current therapeutic paradigms because it does not require implantation of invasive devices, and at the same time, promises to achieve subcellular resolution for repairing connectivity defects that underlie most brain disorders.