Sön 14 jul / År 42 / Nr 3 2024

Innovation for brains: Increasing specificity through biocompatibility

Neuronano AB, a spinout from the Neuronano Research Center (NRC) at Lund University, was created to develop and commercialize innovative electrodes to use in neuromodulation as a treatment for central nervous system disorders, starting with Parkinson’s disease. Neuronano AB is now part of the Cimon Corporation.

Biosensors and deep brain stimulation can allow us to get right inside the brain to learn more about, diagnose and even treat challenging neurological conditions such as drug-resistant chronic pain, Parkinson’s disease, Alzheimer’s disease, dementia, epilepsy and depression.

Bringing academia and industry together
The Neuronano Research Center (NRC) at Lund University and its spinout company Neuronano AB collaborate , thereby providing the necessary connection between basic research and innovative problem-solving, explained Jens Schouenborg, principal inventor at Neuronano AB.
”This relationship works both ways. We can create research tools at Neuronano AB that can be used to provide solutions in basic academic research, and then we can use findings with commercial potential from the NRC and patent, fund and commercialize them through the company. The mix of global and start-up companies, academia and hospitals at Medicon Valley really suits our business model and provides a great example of how industry and academia can meet,”

Meeting the challenges in deep brain stimulation
While deep brain stimulation in diseases like Parkinson’s disease already produces a fast improvement in patients, there are still more challenges to face.
”Inserting electrodes, even those made of non-toxic and biocompatible materials, into the brain causes tissue injury, and the bleeding and inflammation lead to scar tissue formation,” said Schouenborg.
The encapsulation around the electrode is worsened by the use of stiff materials, which further damage the tissue with every breath and heartbeat. The currents in the electrodes then have to be increased to intensify the signal, cutting battery life and increasing the need for re-implantation, as well as making the signal unstable.
”We decided that we needed to reduce the ’kill zone’ by creating “stealth” electrodes that become almost invisible to the immune cells and are mechanically compliant with the soft tissue of the brain,” said Schouenborg.

Finding a solution
The research team at the NRC created bundles of flexible, ultra-thin elastic electrodes that are so lightweight that they can float in the tissue. The next challenge was – how to precisely implant ultraflexible electrodes that bend even in water.
”The solution was to embed the electrodes in dry protein based materials [gelatin] shaped like needles. After implantation, the gelatin dissolves and the electrodes are then positioned as intended in the brain. Interestingly, there was a much smaller loss of neurons than usual, less encapsulation and very few activated microglia. There was also a much lower leakage from the blood-brain barrier, and the brain healed quicker,” said Schouenborg. ”The reduced scarring means that we can use much smaller currents for stimulation and get better recordings.”
Neuronano’s gel technology allows the implantation of any shape of electrode tailored to the application, thereby greatly increasing the areas of application areas. The electrodes can also be hollowed and shaped to contain electronics, optics, genes or drugs, creating highly versatile devices.
Even the most successful approaches to deep brain have shown side effects because of non-specific stimulation, such as blurred speech or sudden laughter. This is because the electrodes stimulate a larger area than absolutely necessary. Because Neuronano’s electrodes are very thin, they can be inserted in bundles and then spread out in the target area. The electrodes within the bundle can then be switched on and off in combinations as required to promote positive and reduce negative effects. The electrodes can also use very small currents, thereby reducing side effects and increasing the life of the implant.
“The team has already obtained proof for these concepts,” said Schouenborg. ”
Neuronano AB is developing its approach to deep brain stimulation in collaboration with the Neuronano Research Center, and hopes to be able to begin clinical trials in three years or less in Parkinson’s disease, and then move on to other areas, for example chronic pain.