Neurodegenerative diseases remain among the leading causes of disability and death worldwide, highlighting the urgent need for neuromodulation technologies that can safely and selectively target deep brain circuits. While existing approaches such as deep brain electrical stimulation or transcranial magnetic stimulation provide clinical benefits, they remain invasive, lack focality at depth, and cannot discriminate between neuronal cell types. At the same time, opto- or chemogenetic methods are not yet clinically translatable. Consequently, many neurological and psychiatric disorders continue to be managed only palliatively.
At this point of the project, BRAINSTORM has successfully achieved all key research objectives and established the technological foundations for a nanoinvasive, wireless neuromodulation platform capable of high spatiotemporal precision. We have developed and validated a novel class of multifunctional, biocompatible magnetic nanomaterials that can be selectively actuated at arbitrary brain depths to generate controlled magneto-mechanical forces and are working on the finalization of implementing localized thermal effects. These bimodal mechanisms will enable targeted activation or inhibition of mechanosensitive or thermosensitive neurons, and are further enhanced through advanced polymer functionalization, piezoelectric coatings, and antibody-based targeting strategies. In parallel, we have prototyped next-generation driving electronics with miniaturized, power-efficient coils and established a focused-ultrasound-based delivery method that enables safe blood–brain barrier passage without intracranial injection. Initial biological testing using calcium imaging and network electrophysiology has confirmed the feasibility of precise on-demand neuromodulation.
In the next phase, these components will be integrated into a unified therapeutic platform and evaluated in complex in vitro models and in vivo in a mouse model of fragile X syndrome. By enabling implant-free, cell-type-selective neuromodulation, BRAINSTORM is on track to overcome major barriers in the treatment of neurological and psychiatric diseases and to lay the groundwork for future clinical applications with significant societal and economic impact.
