Imagine a molecular container where the building blocks are glued together with a substance that’s sensitive to glucose: when glucose levels rise, the substance degrades and the blocks start to fall apart. Then imagine that inside the molecular container is insulin. The higher the glucose level, the more the connections between the building blocks fail—and the more insulin is released through leaks between the blocks. What I’ve just described, in layman’s terms, is the chemist John Fossey’s idea for how to deploy glucose responsive insulin, or GRI.
Fossey runs a research group at the University of Birmingham in England, where he applies chemistry to try to solve real-world problems. Until recently, he knew little about the field of diabetes research. But through an email list, he caught wind of a request for applications put out by JDRF, looking for researchers outside the field who could bring new approaches to developing a GRI. To learn more about the project, he logged into a Webinar run by Dr. Sanjoy Dutta. As Fossey listened to the Webinar, he realized that his lab’s expertise in creating molecules of various shapes could be a good match. “I was listening to the presentation and I thought, This is us! We have this! I didn’t know about this need before.” Afterwards, the two had a conversation. As Dutta recalls it: “I told him what my technical challenges are with GRI, and I said if you can use your expertise to solve one or more of these problems, go for it.” (Dutta explained to me that GRI is one of the areas JDRF has put its muscle behind, both because of the promise of the idea, and because few others are funding it. “It is our firm conviction that if we don’t continue to lead this area, this area will perish. I look at JDRF as oxygen in this field.” And part of that oxygen is bringing in knowledge from new corners of the science world. “We need some non-diabetes research expertise to help us reach our dream. John has a unique battery of expertise that we conventionally don’t work with—chemically activatable GRI. For us it’s a win-win: we could bring a good brain to think about our problem.”
Fossey points out that other researchers have developed insulin-delivery methods that are responsive to sugar in the blood, but this is the first system that would be responsive specifically to glucose. As he explains it: “You can imagine a kind of network that only becomes weak when you reach a certain glucose concentration. The material is progressively eroded. Once glucose goes down, the material goes back to its steady state.”
In a paper published earlier this year in the Royal Society of Chemistry journal Chemical Communications, Fossey and two colleagues described how, using “click” chemistry, they’d designed a structure with a shape that binds specifically to glucose molecules. With the money they’ve received from JDRF, Fossey’s lab will recruit two additional researchers to work on the project.
Both Fossey and Dutta emphasize that this idea is at a very early stage. “GRIs are not a low-hanging fruit,” Dutta says. Right now, Fossey’s lab is working on making sure that the connections between the building blocks making up the insulin pouch are only weakened by high glucose levels—not by other compounds in the blood stream, and that the insulin would be released at the “precise concentration we would need clinically.” If and when this problem is solved chemically, it will need to be tested biologically. Fossey hopes that in about two years time he will reach out to partners who can test the idea on animals. Then the idea would be tested on humans, but first with a harmless “dummy” cargo in the pouch, such as vitamin C. If all goes well, the process might take around seven years. Still, Fossey is optimistic that the idea behind this technology is sound. “I’ve never been so sure of anything as I am that putting these things together should work.”