If you are one of the 23 million Americans who watched the 16 heroic saves by the U.S. goalie facing an incredible barrage of attacks by the Belgian team, I’d bet your heart was racing momentarily …16 times. Mine was, but I didn’t give it a second thought; or rather, I took it for granted. Coming to think of it, other than in Med School I never stopped to think that the vagus nerve, originating from high up in the spinal cord, regulates the movement of the diaphragm -the key to breathing, participates in regulation of my, and yours, heart rate, and is a party to the yin and yang of blood pressure regulation? And what about trivial things like a wheal formation after an insect bite? Or the less trivial function of emptying our bladders? Yes, the peripheral nervous system is involved in that as well. In short, almost every physiological and pathological manifestation of our body reacting to the environment and carrying out commands coming down from the brain depends on the peripheral nervous system. So you would expect us to know a lot about its structure and function, and sometimes malfunction. Just think of it, with nerves inhabiting every millimeter of the body you’d think that drug and device companies would swarm all over it trying to manipulate it, and make a small fortune if they were successful. Until recently, you’d be sadly mistaken. But now the scientific community and the drug industry are waking up to the challenge and potential of the peripheral nervous system.
Behold: a new star is born, and its name is…
Electroceuticals! The pharmaceutical industry has woken up to mother lode of the peripheral nervous system.
Last December GSK (Glaxo SmithKline) announced a $1-million prize for the first team to develop a miniaturized, implantable device that can read specific electrical signals and stimulate an organ to perform a specific function reliably for 60 days (K. Famm et al. Nature 496, 159–161; 2013). The company has spent $50 million on in-house electroceutical research, and it is also funding a consortium of scientists at 25 universities to develop devices that can be made available to the broader research community. Kristoffer Famm, the GSK director of this program, says that the researchers are working on electroceuticals for 20 different disorders that range from cardiovascular disease to rheumatoid arthritis and cancer. “It’s a fascinating time, although we don’t expect all those organs to be a slam dunk,” he says.
To be fair, some implants have been in existence for a long time. We take for granted cardiac pacemakers, but these are actually electroceuticals. They started out as bulky devices, but with the wonders of miniaturization coming along they became implantable. Cochlear implants now enable deaf people to hear conversations and listen to music. Can you top that?
As it turns out -you can. The Food and Drug Administration (FDA) last February approved the first retinal implant for use in the United States. The FDA’s green light for Second Sight’s Argus II Retinal Prosthesis System gives hope to those blinded by a rare genetic eye condition called advanced retinitis pigmentosa.
Retinitis pigmentosa—which affects about one in 4,000 people in the US and about 1.5 million people worldwide—kills the retina’s photoreceptors, the rod and cone cells that convert light into electrical signals transmitted via the optic nerve to the brain’s visual cortex for processing. Second Sight plans to adapt its technology to someday assist people afflicted with age-related macular degeneration, a similar but more common disease. Macular degeneration is an incurable eye disease and that is the leading cause of vision loss for those aged 55 and older in the United States, affecting more than 10 million Americans.
The Argus II includes a small video camera, a transmitter mounted on a pair of eyeglasses, a video processing unit and a 60-electrode implanted retinal prosthesis that replaces the function of degenerated cells in the retina, the membrane lining the inside of the eye. Although it does not fully restore vision, this setup can improve a patient’s ability to perceive images and movement, using the video processing unit to transform images from the video camera into electronic data that is wirelessly transmitted to the retinal prosthesis.
The bountiful results of electroceutical research keep pouring in.
On 1 May, the US Food and Drug Administration (FDA) approved a device by Inspire Medical Systems of Minneapolis, Minnesota, that stimulates airway muscles to treat sleep apnea by regulating breathing while a person sleeps. And on 17 June, an FDA advisory committee recommended that the agency approve a weight-control device from EnteroMedics in St Paul, Minnesota. Implanted between the esophagus and stomach, it stimulates the vagus nerve to make a person feel full.
How is this field different from normal drug development?
In a very basic way; normally scientists work out the pathways, the detailed structure of the proteins involved, the genes coding for the proteins, the transcription factors regulating the genes – and then design drugs to alter abnormalities uncovered in the course of research. Not so in the development of electroceuticals.
“Right now, a lot is based on phenomenology,” says Kip Ludwig, director of neural-engineering programs at the US National Institute of Neurological Disorders and Stroke in Bethesda, Maryland. “You put an electrode in the body, you stimulate, and you get an effect.” In other words, trial and error. This is ass backward, says the NIH, albeit in not so many words. This week, the US National Institutes of Health (NIH) will announce a US$248-million effort to map the body’s electrical wiring and develop such devices. Pharmaceutical giant GlaxoSmithKline (GSK) has already set up a similar program.
Is this the “silver bullet” de jour? I can predict with confidence that the pendulum has always swung, and it will continue doing it. There will be soaring optimism, failures and deep despair, and we’ll end up somewhere in the middle, the good old statistical maxim of reversion to the mean. But judging from the cardiac pacemaker, the cochlear implant and the newly approved retinal implant and the sleep apnea device-the mean ain’t so mean.