FAU researchers experimenting with new therapeutic approach

An international team has succeeded in using a magnetic field to target structures deep within the brain. The researchers injected magnetic nanoplatelets into the relevant region. By doing so, they succeeded in treating movement deficits in mice suffering from Parkinson’s-like symptoms. The new method is less invasive than standard stimulation procedures using implanted electrodes that are currently used to treat certain Parkinson’s disease patients. The study from Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), RWTH Aachen and the Universities of Maastricht (the Netherlands) and Leuven (Belgium) has been published in the journal Advanced Science*.

In Parkinson’s disease, nerve cells in the brain that produce the neurotransmitter dopamine gradually deteriorate. This affects the motor circuits and leads to tremors and other movement disorders. A brain pacemaker may help some patients. This is a small device that is implanted under the collarbone. From there, it stimulates a region deep within the brain called the subthalamic nucleus (STN for short). This changes pathological activity in these neural circuits and can alleviate movement disorders.

“The procedure is relatively complex, however, and not always successful,” explains Prof. Dr. Danijela Gregurec from the Department of Chemistry and Pharmacy at FAU. “This puts many Parkinson’s patients off, and not all patients are suitable candidates for one of these pacemakers.” In future, the new method may prove a less invasive alternative. It can be used to target regions deep within the brain without the need to permanently implant electrodes.

Magnetic particles produce small mechanical forces

“We use magnetic nanoparticles that we implant in the brain,” Gregurec explains. “They have a special shape and a magnetic structure. They were developed in order to transform magnetic fields into tiny mechanical forces.” This is the decisive difference between this approach and traditional deep brain stimulation using a pacemaker. “The traditional method establishes an electrical connection to the brain,” she says. “In contrast, we use the neurons’ natural mechanosensors to influence regions deep within the brain.” If a magnetic field is created around the brain, the nanoparticles react by creating tiny mechanical forces. These forces can slightly deform the cell membranes in their vicinity, similarly to what happens when you press against an inflated balloon with your index finger. This causes small mechanosensitive channels to open up, allowing charged ions to flow into the nerve cells.

The research groups involved in the project tested their methods in animal models. In the animals used for the experiments, the same nerve cells were damaged as in human Parkinson’s patients, which led to similar motor impairments. “Together with our partners from Maastricht, we injected magnetic nanoparticles developed here at FAU into the animals’ subthalamic nucleus,” Gregurec explains. “That is the very region in the brain that is also an important target for conventional deep brain stimulation in Parkinson’s disease.”

Improvement in mice’s movement after stimulation

The particles were injected using high-precision stereotactic methods that allowed them to be placed exactly in the required region of the brain. This precision is essential as the effect depends on the correct motor circuit being targeted. When the animals were exposed to a magnetic field, there was a significant improvement in their motor deficits. “The effect is roughly equivalent to what we would have expected after implanting a brain pacemaker,” says Gregurec.

The magnet particles remained in the brain for a test period lasting several months. In this period, there were no symptoms of inflammation, indicating that they are very well tolerated. Gregurec’s working group is now looking for even less invasive methods that could make the injection into the brain superfluous. One option, for instance, would be to administer the particles in such a way that they can simply be injected into the bloodstream and pass through the blood-brain barrier.

Gregurec’s research team is also investigating options for developing small wearable devices that can create magnetic fields for this stimulation. One option are headbands that patients can put on themselves. However, it will likely still take several years until such approaches can be considered for use in clinical practice. “Nevertheless, we are convinced that the new method has enormous potential,” Gregurec states. “It is not only considerably simpler and cheaper than a conventional brain pacemaker, it is probably also more flexible. Adjusting the parameters of the magnetic field would allow us to control the nanoparticles more accurately.” At the same time, the method is a new research instrument that can be used to investigate how tiny mechanical forces can influence brain function.

Further information:

• Original publication: Remote Magnetomechanical Neuromodulation Uncovers Therapeutic Mechanisms for Alleviating Parkinsonian Symptoms in Freely Moving Mice
  
  *DOI: https://doi.org/10.1002/advs.75097

• Research into Parkinson’s disease at FAU: Molecular mechanisms in Parkinson’s unlocked

• Research on nanoparticles at FAU: Nanomedicine – making the future near enough to grasp

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