Bioelectronic medicine taps into the body’s power to heal

Ludwig arrived at UW–Madison in 2018 as an associate professor in the College of Engineering and the School of Medicine and Public Health. In 2020, he was named the co-director of the Wisconsin Institute for Translational Neuroengineering (WITNe) and in 2023, his tenure home shifted to the Department of Neurological Surgery. His research team within WITNe, known as the Ludwig Laboratory, focuses on developing new neuromodulation therapies, based on electrical stimulation, to treat a wide variety of disorders. Prior to arriving at UW–Madison, Ludwig served as the program director for neural engineering at the National Institutes of Health (NIH), leading the NIH White House BRAIN Initiative programs focused on implantable devices to stimulate and record signals from the central nervous system. He earned his PhD in bioengineering (neural engineering) from the University of Michigan.

You’ve talked about neuromodulation as “hijacking the nervous system” in a way that’s more targeted than drugs. How does that work?

Orally administered drugs have several limitations. The dose goes everywhere in your body instead of just where you need it, and it waxes and wanes in a difficult-to-predict fashion based on your body size, metabolism and a host of other factors. This can cause therapy-limiting side effects and can also cause habituation to the drug over time.

If your body responds to a drug’s biomolecule, it means it has receptors for it and in most cases, can produce its own variant of the biomolecule. The nervous system is a system of wires that pass electrical signals to the body’s organs, telling the body where and when to deliver specific biomolecules. Moreover, the body has its own sensors for the levels of these biomolecules, and naturally changes their concentrations according to where and when they are needed. Bioelectronic medicines, such as neuromodulation, allow us to hack into electrical signals sent by the nervous system, “decode” the level of a biomolecule at any given location, then send electrical signals to increase or decrease the biomolecule according to the body’s need for it. It’s a closed loop.

Why is neuromodulation so important to pursue?

It’s the ultimate in personalized medicine. Our neuromodulation devices are constantly decoding the appropriate and desired concentration of the biomolecule and then passing electrical signals through the nervous system to modulate the concentration as needed. These devices are being used to treat just about any condition you can think of, including hypertension, migraine, heart failure, sleep apnea, overactive bladder, diabetes and cancer. 

Is a neuromodulation procedure invasive?

Originally, yes, these clinical procedures were invasive, requiring surgery to access the nerve that supplies an organ. Now, the devices are wireless and can be reduced to the size of a grain of rice. Our lab has developed versions that can be injected, using non-invasive imaging to guide placement, like getting a shot in the clinic.

What other promising advances can you predict in the field?

To quote the band Bachman-Turner Overdrive, “you ain’t seen nothing yet.” Bioelectronic medicines are the future of individualized or precision medicine and already represent a many-billion-dollars a year global market. Every couple of years, these devices become half the size, half the cost, and twice as powerful at computing. They are the fastest-growing part of the medical device sector and have the potential to completely replace orally administered drugs one day.

How do you describe your work with industry as a research scientist?

While I was employed at medical device company CVRx, my team conceived, developed, and demonstrated the chronic efficacy of a next-generation neural stimulation electrode for hypertension and heart failure in both pre-clinical studies and clinical trials. I participated in the protocol development and execution of those trials, leading to approval for sale in twenty countries for the treatment of heart failure, including the United States. I am a member of the scientific advisory boards for Abbott, Battelle, Presidio Medical and several other companies. I am also a co-founder of Neuronoff, Inc. and NeuraWorx.

You have been at UW–Madison for almost six years — how has your research evolved since your arrival?

My team was lucky enough to have taken two novel bioelectronic medicine therapeutic devices from initial benchtop concepts and computational modeling in 2018, to first-in-human studies assessing safety and human efficacy this past year.

Why is UW–Madison a great place to be working on this?

For one thing, the corridor from Chicago to Minneapolis is known as “medical device alley,” and Madison lies smack in the middle — there here are more than 100 companies focusing on medical device development in our area. I also appreciate the UW School of Medicine and Public Health’s open lab structure, where neurosurgeons, plastic surgeons, neuroscientists, physiologists and a wide variety of engineers share space and interact constantly. This combination makes Madison one of the best places in the world to understand the science of creating devices to hijack the nervous system, and to quickly translate these findings into new therapies.

How did you become interested in your research topic?

When I was visiting the biomedical engineering program at the University of Michigan, I sat next to professor Daryl Kipke at a luncheon. He invited me to visit his lab. They had a demonstration where a rat implanted with a device to record electrical signals from the motor cortex in the brain could play the video game Pong by “thinking,” instead of controlling a joystick. This was intended to help paralyzed individuals type on a computer, by decoding their motor intentions from a wire implanted in the brain.

When the rat was paying attention, it could beat you, because you had to send a signal from your brain to move your muscles, whereas the rat was directly moving the Pong paddle in the videogame with its brain signal. I thought this was the coolest thing I had ever seen in my life, and I immediately changed my entire career focus.

What is one thing your UW colleagues might be surprised to learn about you?

I was a political science and English major for five years before moving into bioengineering. I have worked in industry, government, the non-profit world at Mayo Clinic and am now a tenured academic. I’d love to say this was a cohesive plan, but it was something that evolved over time, and to some extent by accident. I think I’ve gained a diversity of perspective that has allowed me to be much more impactful in this space than if I had only spent time in one sector.