A recent preclinical study highlights a groundbreaking technology that allows for the non-invasive control of specific brain circuits using magnetic fields. This innovation holds significant potential for advancing our understanding of the brain and paving the way for new treatments for various neurological and psychiatric disorders, including Parkinson’s disease, depression, obesity, and chronic pain.
A recent preclinical study showcases a groundbreaking technology that allows researchers to manipulate specific brain circuits non-invasively using magnetic fields. Conducted by scientists from Weill Cornell Medicine, The Rockefeller University, and the Icahn School of Medicine at Mount Sinai, this technology offers the potential to become a potent tool for brain research and to underpin future treatments for a range of conditions, such as Parkinson’s disease, depression, obesity, and complex pain.
The innovative gene-therapy technology is detailed in a paper released on October 9 in Science Advances. In experiments conducted on mice, researchers demonstrated its capability to activate or deactivate targeted neuron populations, resulting in noticeable changes in the animals’ movements. Notably, one experiment successfully lessened abnormal movements in a mouse model of Parkinson’s disease.
“We foresee that magnetogenetics could one day aid patients across many clinical scenarios,” stated Dr. Michael Kaplitt, the study’s senior author, who serves as a professor and executive vice-chairman of neurological surgery at Weill Cornell Medicine and heads Movement Disorders Surgery at NewYork-Presbyterian/Weill Cornell Medical Center.
The collaborative study involved Dr. Kaplitt’s lab and the teams of Dr. Jeffrey Friedman, the Marilyn M. Simpson Professor in Molecular Genetics at The Rockefeller University, and Dr. Sarah Stanley, an assistant professor in the Medicine Department at the Icahn School of Medicine at Mt. Sinai.
Dr. Santiago Unda, a postdoctoral researcher in Dr. Kaplitt’s lab, was the lead author of the study.
The ability to control brain circuits in real time while allowing normal movement in animals or humans has long been a goal for neuroscientists, though it presents substantial challenges. Currently, optogenetics technology can instantaneously switch specific neurons on or off using light pulses, but it necessitates invasive equipment to direct the light into the brain. Similarly, deep brain stimulation can adjust brain regions but requires permanent implantation of a device and strives for greater accuracy.
Having conducted initial studies on magnetogenetic technology as an alternative to existing methods, Dr. Friedman and Dr. Stanley collaborated with Dr. Kaplitt, who is recognized for his work in brain-targeted gene therapies, to create a method anticipated to have clinical applications.
This innovative method utilizes gene therapy to introduce an engineered ion-channel protein to specific neurons. This ion channel protein functions like a switch that can turn neurons on or off and is responsive to magnetic fields due to its incorporation of a protein that adheres to ferritin, a natural iron-storing protein. While the gene therapy is administered to targeted brain areas via minimally invasive surgery, a sufficiently strong magnetic field can manipulate the ferritin-trapped iron atoms to open or close the channel, activating or inhibiting the neuron based on its design, without needing an implanted device or medication.
In one experimental setup, the team injected the gene therapy for the magnetically responsive channels into specific neurons in the striatum, a region responsible for movement control, in mice. Subsequently, they utilized the magnetic field from an MRI machine to activate the neurons, significantly slowing or even halting the mice’s movements. In another test, they decreased neuronal activity in the subthalamic nucleus, which helped alleviate movement disorders in a mouse model of Parkinson’s disease.
The researchers found that their method remains effective even when using a smaller and more affordable “transcranial magnetic stimulation” device, which is commonly employed in clinics for treating depression, migraines, and other conditions.
The trials did not reveal any safety concerns, and the researchers emphasized that typical ambient magnetic fields are far too weak to accidentally activate magnetogenetic switches.
The research team plans to further investigate potential clinical uses, including treatment for psychiatric disorders and chronic pain affecting peripheral nerves. They are also committed to refining and advancing the magnetogenetics technology itself.
“Having the ability to perform directional manipulation of brain activity with this relatively uncomplicated system is crucial for enhancing our understanding of the principles involved and further advancing this new technology,” Dr. Unda remarked.
Many physicians and scientists at Weill Cornell Medicine maintain collaborations with external organizations to promote scientific innovation and offer expert insights. The institution publicly discloses these affiliations to maintain transparency. For additional information, please see Dr. Michael Kaplitt’s profile.
This research received funding from the National Institute of Neurological Disorders and Stroke and the NIH Office of the Director, both part of the National Institutes of Health, through grant numbers R01NS097184, OT2OD024912, and the JPB Foundation.
