Do a web search for the term “electroceuticals,” and many of the results tout a form of alternative medicine. GlaxoSmithKline PLC is angling to make the term a lot more mainstream.

A new funding initiative from the drug giant aims to back academic scientists who are trying to answer early questions about the possibility of using extremely focused electrical impulses to modulate the neural signals that control vital organs. GSK unveiled the project in the April 10 issue of Nature; the international drug firm will start fielding proposals immediately and fund up to 40 researchers across 20 academic and other nonprofit institutions for one year.

The longer-term goal is to do with miniscule electric pulses what drugmakers currently try to do with biologics and small molecules: control blood pressure, cytokine production, glucose function, or any number of biological mechanisms that lead to disease when out of whack. “Correcting disorders with treatment in their own electrical language” is how the authors of the Nature paper describe their goal.

Before treatments come to light, however, there are years of work ahead in mapping the neural activity associated with various diseases. Kristoffer Famm, PhD, the vice president in charge of GSK’s new bioelectronics group, says the funding, to be parceled out to two researchers per lab, is aimed at jump-starting the mapping projects or building upon works in progress. GSK is not revealing the amount it has earmarked for the 40-researchers phase of the project. But at the end of 2013, GSK expects to convene a meeting and ask researchers to zero in on a key hurdle the field needs to overcome; GSK will then put up $1 million as a prize to the group that solves the problem.

Even without GSK’s money, the field is enjoying momentum. Famm says there has been “huge progress in recording the activity of peripheral nerves to control prosthetic limbs.” The new brain-mapping initiative introduced in early April by President Barack Obama should help multidisciplinary teams of biologists, engineers, and bioinformatics specialists build new tools to record and decode the flow of information through other neural circuits. In the same issue of Nature as GSK’s electroceutical commentary, a Stanford University team reported they have devised a method to make brains transparent (ones that are study subjects, not ones still attached to their owners) and allow researchers to highlight and study networks of neurons as they fire.

Famm’s co-authors are also leading the way. One advance comes from the University of Pennsylvania lab of Brian Litt, MD, which specializes in translating neuroengineering research into patient care. In conjunction with other labs, the Litt lab is developing flexible, ultrathin sheets of electrodes that conform to the irregular shape of brain tissue and record neural activity, such as epileptic seizures.

The other co-authors are Kevin Tracey, MD, president and CEO of the Feinstein Institute for Medical Research and a specialist in neural control of the immune system; Edward Boyden, PhD, a biological engineering professor at the Massachusetts Institute of Technology; and GSK chairman of global R&D Moncef Slaoui, PhD.

Boyden’s synthetic neurobiology group has created “optogenetic” tools that, using lasers and fiber optics, deliver light into the brain to control the physiology of specific cells and manipulate the activity of neural circuits. The work has brought Boyden recent accolades and a share of the 2013 Grete Lundbeck European Brain Research Prize.

That doesn’t guarantee Boyden a share of GSK’s cash, however. Famm’s academic co-authors will have to submit proposals like everyone else. But Famm says they all share a vision of what so-called electroceuticals could be. Ultimately, they want to see closed-loop systems: devices attached to a key point in a neural circuit that read the impulses in the context of a patient’s physiological disease state, analyze the data, and change the signals on the fly to create therapeutic benefit. “But these closed-loop therapies can be realized only if the required disciplines come together early on,” the authors write in Nature, citing neuroscience, bioinformatics, bio- and electrical engineering, nanotechnology, and more.

“We want to focus our effort and bring those tools to control of organs involved in traditional areas like inflammatory and respiratory disease, cardiovascular disease, and see how much through neural control we can reverse them,” says Famm.

Famm sees the electrical signals as musical notes and the neurons as piano keys. “How much do you have to get down to the individual nerve fibers?” he asks. “Will we have to ‘play’ each fiber separately or hit them all?”

Famm’s bioelectronics group, which reports directly to Slaoui, hopes to serve as the hub for much of the activity in the space the next few years. Its first-year seed funding has few strings attached. All intellectual property that arises from the work will remain with the inventors, as long as they agree to grant GSK non-exclusive licenses it can then share with others in the research network. “GSK will play matchmaker and get collaborators together,” says Famm.

Once the early work of building the circuit maps is well along, GSK and others can start choosing appropriate therapeutic areas to pursue and building device prototypes. In the Nature commentary, Famm and his co-authors write that early prototypes “might use microchip-controlled electrode arrays similar to those used today in interfaces for prosthetic limbs to modulate neural signals. Second-generation micro- and nanoscale devices may instead leverage light, or mechanical or magnetic energy to achieve such modulation in specific cells within targeted circuits.”

The effort will build upon the fast-growing use of neuromodulation across many diseases. (SeeAlso see "Neuromodulation Market: Innovation Brings High-Growth Rewards" - Medtech Insight, 27 March, 2013..) Various interventions are showing clear disease benefit, says Famm, and are a nice proof of principle. But therapies like deep brain stimulation, pacemakers, or vagus nerve stimulation are still rather blunt instruments. “They still need a lot of improvement,” Famm says. “In the future, we’re talking about latching on to a specific point in a neurocircuit,” perhaps even targeting individual cells within a circuit.

All humans have the same neural circuitry leading into and out of their organs, but at this point researchers don't know how much the signals within the circuits vary, even among patients with the same disease. “How much the signature looks the same between individuals, or between animal models and humans, is a big question to resolve,” says Famm. In other words, if electroceuticals become a reality, will they become as personalized as some people believe pharmaceuticals will become?

Another big question is how fine-grained the impulses need to be. Will the treatments need to go after individual cells, or can they target a group of cells that have a common function? Famm sees the electrical signals as musical notes and the neurons as piano keys. “How much do you have to get down to the individual nerve fibers?” he asks. “Will we have to ‘play’ each fiber separately or hit them all?”

With Academic Collaborators, GSK To Plug For ‘Electroceuticals’

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