Drawn together: a magnetic collaboration in Parkinson’s research

A cross-disciplinary collaboration between three researchers in the Yang Tan Collective is breaking new barriers in Parkinson’s disease research and therapeutics development.

Led by Ye Ji Kim, a recent PhD graduate from MIT’s Department of Materials Science and Engineering, in collaboration with postdoctoral fellows Sharmelee Selvaraji of the K. Lisa Yang Brain-Body Center and Antoine De Comite of the K. Lisa Yang Integrative Computational Neuroscience (ICoN) Center, the team is developing a groundbreaking, minimally invasive therapeutic strategy for Parkinson’s — one that could eventually replace deep brain stimulation.

Even the team’s approach to gathering data is innovative, with the potential to be used in many other applications.

As part of her PhD research, Kim designed special magnetoelectric nanoparticle discs — MENDs for short — capable of activating a targeted brain area. Measuring just 250 nanometers across (1/500th of the width of a human hair), the discs can be injected into the brain and activated by a weak magnetic field applied outside of the skull.

“Currently, tremors in Parkinson’s patients can be treated with invasive deep brain stimulation electrodes that must be surgically implanted deep in the brain,” explains Kim. “Our nanoparticle discs are a much less invasive way of stimulating the brain and potentially alleviating motor symptoms.”

In this stage of the project, Kim, Selvaraji, and De Comite are testing a novel treatment protocol on mouse models engineered to have motor deficits mimicking Parkinson’s hallmark symptoms.

To measure tremors on such a small scale and establish if the discs can indeed improve symptoms, the team needed to create a whole new array of measurement and data collection tools.

The closest commercially available gear was intended for much larger animals and could not capture a wide range of motion.

The collaborative expertise between Kim and De Comite made the precision tracking system sensitive enough to track minute movements in mice in a full range of motion. De Comite developed a sophisticated computational pipeline with Kim’s input, based on computer vision methods that extract subtle gait features such as velocity, step length, and coordination across legs, which was then incorporated into Kim’s experimental design.

“It was a very exciting point for me to see the new system that Antoine developed working so well,” Kim says.

The entire collaboration is a story of serendipity and courage.

When this project was initiated, Selvaraji joined the Brain-Body Center from the National University of Singapore, where she had completed all her previous degrees. Kim says, “I needed someone to discuss ways to assess and enhance the precision and impact of my new project involving a disease model that was quite new to me, and Sharm was there. The dynamic between us was incredibly synergistic. We kept exchanging ideas.” Selvaraji was looking around for a suitable postdoctoral experience in neuroscience when a former classmate suggested the position in Polina Anikeeva’s materials science and engineering lab at MIT. Selvaraji was initially appointed to a fellowship made possible by supporters Pappudu Sriram and Rajesh Venkataramani.

“I’m a molecular neuroscientist, and I have no prior expertise in engineering,” Selvaraji says. “I didn’t expect my expertise to fit into an engineering lab, but it turned out to be a natural complement to the team’s vision, as Polina [Anikeeva, director of the Brain-Body Center] was looking for a neuroscientist to bring a biological perspective to the team.”

Selvaraji’s fascination with neurological diseases began when she was a child. After reading a newspaper article with a captivating illustration about addiction, she realized “what a black box the brain was.” Her enthusiasm gradually transformed into her career as she delved deeper into neuroscience in her university years. Since then, she’s also worked on research pertaining to neurodegenerative diseases such as Alzheimer’s disease, vascular dementia, and Parkinson’s disease.

“This treatment could potentially give someone with advanced Parkinson’s some level of independence back,” Selvaraji adds. “Being able to show a small but meaningful change in animal models is a huge step forward.”

When De Comite first analyzed the movements of mice implanted with MENDs, the results truly surprised him. “I never thought the motor deficits could be affected so much by the disc activation,” he notes. He believes the team’s approach could extend far beyond Parkinson’s. “The method we’ve developed could be used for many other neurological diseases and in other species.”

Like Selvaraji, De Comite landed in his lab by luck and fearlessness. He completed his engineering and PhD degrees in Belgium before spending a few months at Western University in Canada as a visiting graduate student. While there, a professor suggested that he “be bold” and contact new faculty member Nidhi Seethapathi at MIT —without a formal introduction.

De Comite notes, “We’re not working to solve the problem of motor deficiencies (though that is the ultimate goal). We’re helping to make them less extreme than they would be without treatment.”

Like her collaborators, Kim hadn’t originally planned to take the path that brought her to MIT. She had planned to work in the clean energy industry, until her master’s degree research on nanostructure fabrication for efficient electrochemical reactions — and their application in low-carbon, hydrogen-based energy systems — changed her direction. Through that experience, she realized she was deeply drawn to designing her own tools and materials to advance fundamental scientific discovery.

“Prof. Anikeeva’s group looked like a good group, [where] I could invent my own materials and help many people suffering from various neurological and psychiatric conditions,” she says. Kim says, “Bridging these two extremely different areas of expertise — Sharmelee’s molecular neuroscience and Antoine’s biomechanics — was great fun and turned what I once thought was science fiction into a reality.”