These devices are medically revolutionary, and they represent just a small sample of what is possible for bioelectronic medicine, says neurosurgeon Kevin Tracey, president of the Feinstein Institute at North Shore LIJ Health System in New York. In the late 1990s, Tracey discovered that stimulating the vagus nerve also alters immune function. A company he later founded, SetPoint Medical, discovered that stimulating the nerve could stop inflammation to fight rheumatoid arthritis.
“We found that the immune system functions as an innervated organ just like the heart,” says Tracey.
It was a game changer. Autoimmune diseases — such as rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and lupus — now could be treated electrically. SetPoint Medical went on to develop the first bioelectronic devices to treat rheumatoid arthritis. In 2012 the company announced results from the first clinical trial for European patients with rheumatoid arthritis, with eight people participating in the trial and nearly two-thirds experiencing benefits.
Tiny and Mighty
To develop new bioelectronic therapies, scientists must first map the neural circuits and determine patterns of neural firing that correspond to healthy organ function. Then they need to figure out how those patterns go wrong to cause disease. To that end, the National Institutes of Health has invested $248 million over the next six years toward mapping the detailed wiring of the nervous system.
Neurons also have characteristic patterns of electrical impulses, akin to the dots and dashes in Morse code, and neuroscientists are investigating them to determine how they malfunction to cause disease and how to restore the pattern displayed in a healthy body. Meanwhile, research on brain-machine interfaces is producing electrodes that can interact with individual neurons, giving scientists more precise control of neural circuits than ever before. And scientists are designing microchips based on brain function, to make them work more intuitively.
Engineers are also working to miniaturize bioelectronic devices, lowering the risk for patients when the devices are surgically implanted. When surgeons wrapped Kessel’s half-dollar-size electrode around the carotid sinus, for example, they had to dissect around many nerves — a procedure that carried a large risk of nerve damage.
To keep patients safer, biomedical engineer Kip Ludwig, who worked at CVRx years after the start of Kessel’s trial, and his colleagues spent several months using computer models to design a far smaller device. They tested prototypes in laboratory animals and worked with vascular surgeons to see how the design would impact the surgical procedure and to better understand the physiology of the process. The company also performed “benchtop” simulations on a prototype that mimicked worst-case scenarios — such as bending and stretching of the device — to ensure it would stand up to normal wear and tear over a lifetime of use and wouldn’t degrade and release harmful substances.
The result was a durable electrode 8 millimeters across, about the diameter of a pencil eraser, that surgeons can implant on the carotid artery with just a tiny incision, and a longer-lasting battery that minimizes replacement operations. Another CVRx team shrank the battery-powered generator by about half to roughly the size of a USB thumb drive. In August 2013, Kessel had the newest version of the device implanted, and it works as well as the original.
The goal of streamlining useful but clunky bioelectronics actually drives the whole industry right now, says Ludwig, who has since left CVRx and is now the program director for neural engineering at the National Institutes of Health, where he allocates money to other bioelectronics researchers to develop smaller, more effective devices.
Second Sight, a bioelectronics company in Sylmar, Calif., uses electrodes to stimulate the retina, and the devices have partially restored sight in nearly 100 patients. New cochlear implants now allow deaf people to have phone conversations. Last year, a Columbus, Ohio-based team implanted an electrode in a paralyzed man’s brain and connected it to a sleeve on his wrist, effectively allowing the man to move his hand with only his thoughts.
Bioelectronics could one day even help people with paraplegia walk. University of Alberta researchers are conducting clinical testing this year that will involve two patients with severe spinal cord injuries. A temporary bioelectronic device implanted on the lower spinal cord will transmit electrical impulses, mimicking brain signals, from below the spinal injury to the legs. They hope the device will result in mobility.
“I don’t think we’ll get to the point where a drug will make a blind person see and deaf people hear,” Ludwig says. But “that’s what we’re seeing with these devices.”