The Pulsing Pharmaceutical: Bioelectronics

GSK Lights a Spark around Bioelectronics

Dominating the frontier of medicines discovery is a simple, endlessly challenging question: if not a drug, then what?  Industry science has evolved from the chemical roots of the small molecule to the biologics synthesized from living organisms, but the delivery mechanism – pill or injectable – is basically the same. Today, there is promise in new approaches that rely on the “other language of biology,” using the human body’s own circuitry of cells and nerves to induce precisely targeted therapeutic effects against a range of debilitating diseases.

A model test of this approach is the budding field of bioelectronics, which builds on the body’s in-house battery charger of electrical pulses, transmitted through billions of nerve fibers, to restore the healthy functioning of damaged tissues, organs or functions. “Electroceuticals” already exist in a primitive state, such as deep brain stimulation for Parkinson’s disease, but tend to mimic the actions of conventional drugs in lacking a precise targeting capability, in this case against specific cells within an identifiable circuit of activity. And because the approach is so scattershot, it can lead to unanticipated side effects, with overall marginal benefits to patients.

Significantly, new research tools like optogenetics, which allows scientists to observe activity of individual nerves in living tissue, are being combined with increased computational “big data” capacity to identify ways to model and manipulate neural signals against hypothetical disease states, in a controlled laboratory setting. It’s largely a mapping exercise, analogous to the Human Genome Project, albeit one that is writ on a much smaller stage, even though the scientific potential might be equally as great.

What the field lacks is a convener – but now one big Pharma player is stepping up to the plate. The business angel is GSK; more specifically, its global Chair of R&D and Vaccines, Moncef Slaoui, a PhD in molecular biology who began investigating bioelectronics as a treatment pathway shortly after assuming his post in 2006. “I see it as a new layer of opportunity beyond the conventional biochemical approach that has defined developments in our field for the last century,” Slaoui told PharmExec.

An advocate of this and other forms of “new science,” Slaoui shares with company CEO Andrew Witty a desire to upend the traditional notion of what constitutes medicines research, particularly by bringing different scientific and functional disciplines to the table. It’s a world where progress in finding cures and treatments may depend as much on process improvements through materials engineering as it does on the standardized chemical assay. “Bioelectronics represents the new frontier in multi-disciplinary collaboration, which is another reason why we find it so appealing,” Slaoui says.

Partly because the science is so new, GSK is taking a low-key stance as a facilitator of ideas rather than trying to dictate the terms of engagement. “Our objective is to add value, and we do that in two ways: by encouraging more scientific diversity in the field, and helping prioritize a few practical outcomes thorough funding and partnerships that animate a spirit of co-ownership.”

Slaoui himself made a series of visits to academic research centers in the US and abroad as a form of due diligence; the next step was to establish, in April 2013, a dedicated Bioelectronics R&D unit under the R&D Group’s Exploratory Funding strategy, providing modest grants to support critical early-stage projects in emerging areas of science.

To date, 15 projects have been approved with six leading academic institutions, including Duke, the University of Pennsylvania, the Feinstein Institute, Academic Medical Center of Amsterdam, and the NOVA Medical School in Lisbon. The grants average a few million dollars each, and will consider, among other things, how nerves in the body relate to particular diseases, to understand the “firing patterns” of these nerves, and identifying new technologies to enable a better interface with the nerves and nerve fibres.

Conditions being studied include rheumatoid arthritis and inflammation sensing, overactive bladder, inflammatory bowel disease, and type 2 diabetes. “The brain is a peripheral area to us, because of its daunting complexity. We think bioelectronics has its most promising applications in areas like metabolic disorders, weight loss, and inflammation, particularly in tracing signals that link this latter condition to the onset of cardiovascular disease,” Slaoui notes.

Prize time

To further spark the creative process, GSK on December 16-17 sponsored an invitation-only Bioelectronics Medicine Summit in New York. It brought some 150 world-class researchers from the US and abroad together to review the state of the art and help prioritize what needs to be done to bring bioelectronics closer to the point where testing against specific conditions can begin.

But the key goal of the event was to identify one specific project to answer the following question: what is the most critical hurdle to overcome in achieving the vision of the first bioelectronic medicine? The agreed answer: “Creating a miniaturized, fully implantable device that can read, write and block the body’s electric signals to treat disease.”

This is what is needed first to ensure onward development of bioelectronic medicines as a future therapeutic reality. Said Slaoui, “it’s a task not as easy as it may seem.  Any such device must be powered by an energy source that is compatible with life inside the body. A battery is non-compatible because it generates heat, while glucose might hold promise because it is water-based. Rejection by the body is another big hurdle, and it is especially important because any device to be useful will have to inhabit the body for a long time.”

The next step is for an affiliated expert review committee to set parameters for individual proposals, review submissions and award the challenge grant of $1 million. To start the process, the prize project parameters will be posted online, on February 1, at www.gsk.com/bioelectronics. Award of the prize is set for mid year and will be announced simultaneously with a white paper summarizing conclusions of the December summit.

Practically speaking, how far away is this work from reality – is bioelectronics the ultimate pipedream in big pharma’s often absurdly over-promised pipeline? So far, Slaoui is playing the optimist. “Assuming we continue to collaborate, I think we are just 10 years away from being able to take these concepts forward toward commercialization.”