TECNALIA is leading the development of a groundbreaking prototype for non-invasive neuromodulation for diseases such as stroke and Parkinson

The applied research and technological development center TECNALIA has led the development and validation of a groundbreaking prototype focused on ultra-precise neural stimulation through the excitation of selective nanoparticles using light and magnetic fields from outside the body—that is, in a non-invasive manner—opening up a new avenue for treating neurological diseases such as stroke and Parkinson’s disease without the need for surgery.

The non-invasive tools available to date—such as Transcranial Magnetic Stimulation (TMS) or Transcranial Electrical Stimulation (TES)—have significant limitations in terms of resolution and depth, while pharmacological solutions are largely ineffective, particularly due to their inability to cross the blood-brain barrier (a barrier that regulates the passage of substances between the bloodstream and the brain, protecting the central nervous system), as this structure protects the brain but also prevents many drugs from reaching the neural tissue where they are supposed to act, thereby reducing the efficacy of current treatments.

Experimental phase

This development, led by TECNALIA and known as the Neumonas project, enables selective, deep, multifocal, and safe neuromodulation without the need for surgery. Its potential clinical applications range from repairing brain damage to strengthening weakened neural connections. Furthermore, its intuitive and affordable design facilitates its use in preclinical research, integrating all modules into a single platform for experimentation in rodents.

As explained by Ander Ramos, TECNALIA’s principal researcher in medical technologies and head of the neurotechnology research group, “the human brain—which has as many neurons as there are stars in the Milky Way and a network of connections three times larger than the entire Internet—can lose functionality due to conditions such as stroke or Parkinson’s disease. The possibility of modulating its activity from the outside, without surgery and with precision, opens up a completely new therapeutic horizon.”

The system is based on two types of nanoparticles, designed and developed by Marek Grzelczak’s team at the Center for Materials Physics (CFM, a joint CSIC-EHU initiative), which are between 100 and 10,000 times smaller than a neuron. On the one hand, there are gold nanoparticles, which convert light into heat to activate neurons. On the other hand, there are magnetic nanoparticles—developed in collaboration with Maite Insausti’s team at the University of the Basque Country (EHU)—which convert magnetic energy into heat. Both types of nanoparticles are functionalized to facilitate their guidance to target cells, thanks to the work of Mónica Carril’s group at the University of the Basque Country (EHU) and the Basque Bio-Medicine Foundation (FBB).

At the Donostia International Physics Center (DIPC), the team led by Aitzol Garcia-Etxarri carried out the theoretical simulations required to design the nanoparticles, which were later validated by TECNALIA through experimentation, as well as the calculations needed to determine and control the conversion of light and magnetic energy into heat.

As Ramos points out, “to facilitate the nanoparticles’ delivery to the affected area, the system allows for the opening of the blood-brain barrier in a controlled, precise, and reversible manner.”

TECNALIA has installed the prototype at the CSIC’s Sols Morreale Institute for Biomedical Research and validated it in mice thanks to preclinical work conducted with Abraham Martin’s team at the Achucarro Basque Center for Neuroscience. The validation has yielded very promising neuroprotective results in both stroke (reducing the risk of death and lesion volume) and Parkinson’s disease (halting progression and improving symptoms), so “the next logical and necessary step is to move it to humans,” says Ramos.

Furthermore, in preparation for this transition, a neuromodulation monitoring system for humans has already been developed (with the help of Luis Montesano’s team at Bitbrain Technologies) and validated in patients with Parkinson’s disease (thanks to collaboration with Maricruz Rodriguez’s team at the University Clinic of Navarra), based on high-density electroencephalography (a sensor-equipped cap that takes less than 5 minutes to put on and calibrate), which allows for the detection and monitoring of deep neural activity in real time.