Electrical deep brain stimulation (DBS) is a well-established method for treating disordered movement in Parkinson’s disease. Nevertheless, implanting electrodes in an individual’s brain is an invasive and imprecise method to stimulate nerve cells. Researchers report in ACS’ Nano Letters a brand new application for the technique, called magnetogenetics, that uses very small magnets to wirelessly trigger specific, gene-edited nerve cells within the brain. The treatment effectively relieved motor symptoms in mice without damaging surrounding brain tissue.
In traditional DBS, a battery pack externally sends electrical signals through wires, activating nerve cells in a region of the brain called the subthalamic nucleus (STN). STN activation can relieve motor symptoms of Parkinson’s disease, including tremors, slowness, rigidity and involuntary movements. Nevertheless, since the potential unintended effects, including brain hemorrhage and tissue damage, could be severe, DBS is generally reserved for individuals who have late-stage Parkinson’s disease or when symptoms are not any longer manageable with medication. In a step toward a less invasive treatment, Minsuk Kwak and Jinwoo Cheon worked with their colleagues to develop a wireless method to effectively reduce motor dysfunction in individuals with Parkinson’s disease.
For his or her wireless technique, the researchers tagged nanoscale magnets with antibodies to assist the molecules “stick” to the surface of STN nerve cells. Then they injected the sticky magnets into the brains of mice with early- and late-stage Parkinson’s disease. Prior to the injection within the STN, those self same nerve cells had been modified with a gene that caused them to activate when the modified magnets on the cell’s surface twisted in response to an externally applied magnetic field of about 25 milliteslas, which is about one- thousandth the strength of an MRI.
In demonstrations of the magnetized and modified neurons in mice with Parkinson’s disease, the mice exposed to a magnetic field showed improved motor function to levels comparable to those of healthy mice. The team observed that mice that received multiple exposures to the magnetic field retained greater than one-third of their motor improvements while mice that received one exposure retained almost no improvements. Moreover, the nerve cells of treated mice showed no significant damage in and across the STN, which suggests this could possibly be a safer alternative to traditional implanted DBS systems, the researchers say. The team believes its wireless magnetogenetic approach has therapeutic potential and could possibly be used to treat motor dysfunction in individuals with early- or late-stage Parkinson’s disease in addition to other neurological disorders, akin to epilepsy and Alzheimer’s disease.
The authors acknowledge funding from the Institute for Basic Science.
