Researchers have developed a gene therapy technology that uses magnetic fields to switch groups of neurons on and off, controlling brain circuits affected by Parkinson’s disease. In addition to Parkinson’s, the tech could be used to treat conditions as diverse as depression, obesity, and chronic pain.
As science and technology have advanced, so, too, have gene therapies to treat brain conditions. Optogenetics, for example, delivers light-sensitive proteins into specific nerve cells, or neurons, controlling brain circuits by switching neurons on and off using light. But it requires a fiber optic implant.
Magnetogenetics achieves the same outcome using magnetic fields. Researchers from Weill Cornell Medicine, The Rockefeller University, and the Icahn School of Medicine at Mt. Sinai have collaborated to develop a gene therapy that uses magnetic fields to precisely control specific brain circuits in real-time without needing an implanted device.
“We envision that magnetogenetics technology may someday be used to benefit patients in a wide range of clinical settings,” said Michael Kaplitt, professor and executive vice-chairperson of neurological surgery at Weill Cornell and the study’s co-corresponding author.
Ion channels are particular proteins with characteristics that allow them to assemble into channels. The function of ion channels is to allow specific inorganic ions – primarily sodium (Na+), potassium (K+), calcium (Ca2+), or chloride (Cl-) – to pass in and out of a cell through the plasma membrane. In neurons, this enables electrical signals to pass from one neuron to the next.
The researchers engineered an ion channel protein with a protein nanobody that sticks to a natural iron-trapping protein called ferritin. When the gene therapy is delivered to a particular brain region through minimally invasive surgery, a sufficiently strong magnetic field exerts enough force on the ferritin-trapped iron atoms to open or close the ion channel – switching the neuron ‘on’ or ‘off’.
In the present study, the therapy was delivered to neurons in the movement-controlling striatum region in mouse brains. When the magnetogenetic tech was activated by exposure to the magnetic field from a magnetic resonance imaging (MRI) scanner, the mice’s movements were slowed significantly and even froze.
In another proof-of-concept experiment using mouse models of Parkinson’s disease, the researchers delivered the tech to neurons in a brain region called the subthalamic nucleus. In humans, deep brain stimulation (DBS) targets that region to reduce the motor fluctuations or tremors caused by the condition. Applying a magnetic field to switch on the technology in the mice significantly reduced movement abnormalities.
The researchers found that their method worked just as well using a smaller, less expensive magnet than that found in an MRI machine: a transcranial magnetic stimulation (TMS) device used to treat patients with depression, migraine, and other conditions in the clinic. They observed no safety issues with their method.
“Being able now to do directional manipulations of brain activity with this relatively simple system is going to be very important in helping us better understand the underlying principles to help further advance this new technology,” said Santiago Unda, a postdoctoral researcher in Kaplitt’s lab and the study’s lead author.
The researchers plan to explore clinical applications of their magnetogenetic therapy, including treatments for psychiatric conditions and even chronic pain. They’ll also continue optimizing the technology.
The study was published in the journal Science Advances.
Source: Weill Cornell Medicine
