While many diabetes researchers are focusing on treatments and possible cures using nanotechnology, implantable devices, and even DNA manipulation, one researcher is attracting attention and making real progress by tackling the issue old school.
“Insulin is the answer to multiple issues facing people with diabetes,” says Dr. Michael Weiss, Chairman of Biochemistry & Molecular Biology and Director of the Center for Chemical Biology at Indiana University. To translate his academic studies, he became a founder of Thermalin, Inc., a company working on new types of insulin optimized for specific unmet needs. “Insulin, in many cases, is the key to really prolonging and improving life for people with diabetes.”
Weiss recalls that as a medical student in his 20s it was not uncommon to encounter young adults with diabetes coping with wide ranging and significant medical issues, such as blindness, renal failure, and other, at the time common, complications from suboptimal glycemic control—often poor by current standards.
“Compare now to forty years ago,” he says. “There has been a series of stepwise improvements that are extending life. Blood testing is much more common of course, and also improved methods to monitor glucose levels. The advent of insulin analogs has also been helpful. The pace of innovation year-to-year has seemed slow, but the cumulative impact has been extraordinary. Yet there is still so much more to be done.
“Every year we learn something new about insulin, which was discovered in 1921. But even today, how much do we really know about the fundamental mechanisms of signaling, especially from one organ to the next? How much more can be learned! And the clinical implications of this new knowledge, when translated, will surely be enormous.”
Weiss and his team of twenty-two scientists and colleagues at Thermalin are working to decipher new aspects of insulin analog pharmacology at their headquarters in Cleveland, Ohio. They are developing several new promising kinds of insulin. Their projects could have far-reaching implications for improving diabetes care and possibly even lead to a “cure” by providing more human-like insulin for use in an improved insulin pump, or artificial pancreas.
In his academic laboratory in Indianapolis and at Thermalin, Weiss is spearheading projects that include working on an ultra-rapid insulin; an insulin patch; an ultra-concentrated insulin; a glucose-responsive insulin; an oral insulin and, finally, insulin that does not require refrigeration and indeed could withstand temperatures as high as 55 degrees Celcius, or 131 degrees Farenheit.
It was this last idea, engineering an ultra-stable insulin that wouldn’t need refrigeration, that signaled the first step in the insulin odyssey that has defined Weiss’s professional life for more than three decades.
Thirty-five years ago, when he was a graduate student at Harvard, Weiss went to Kenya and saw people burying insulin in clay pots to keep it from degrading and becoming less effective, or outright ruined, in the searing heat. Weiss started studying insulin with the idea of coming up with an insulin formulation that would be heat-resistant and thereby help people in Africa and other regions of the developing world lacking access to electricity or refrigeration. Under-estimating the subtlety of the problem, he figured he could come up with something fairly quickly.
More than three decades later, Weiss is still working to re-engineer an analog of insulin that would exhibit marked heat resistance while retaining native biological activity.
“We recently made a prototype molecule that is working,” Weiss says in relation to a pair of articles he and his team published in the Journal of Biological Chemistry in January. “We are moving forward on that.”
Manipulation of the insulin molecule is the cornerstone of Thermalin’s business plan and its efforts to develop novel insulin formulations.
Another project Weiss is leading is designing a so-called “smart” insulin that responds to glucose levels. That effort, initiated at the Case Western University School of Medicine (where Weiss was previously Chairman of the Department of Biochemistry and now being continued at the Indiana University School of Medicine, in January received a $2.5 million, three-year grant from the Helmsley Charitable Trust. That award follows a previous $1 million grant to the same program in 2013.
“We’re very pleased to continue our partnership with the researchers at Case Western Reserve and Indiana University who are on the vanguard of changing the lives of people with T1D,” said Gina Agiostratidou, Director of the Harry B and Leona M Helmsley Charitable Trust’s Type 1 Diabetes Program in a news release. “Intelligent insulin can take not only much of the worry out of managing blood sugar, but much of the health risk as well.”
The Helmsley Charitable Trust is not the only organization to recognize Weiss’s efforts and to back his efforts with research grants or direct investment. Thermalin and other efforts involving Weiss have been funded by, among others, JDRF, the National Institutes of Heath, and, most significantly, via a research partnership between Thermalin, Inc. and French pharmaceutical company Sanofi.
In September Sanofi announcedtheir official collaboration with Thermalin, along with an effort to help raise for $17.5 million for the company. In that announcement Weiss said, “This alliance will allow us to move our advances in insulin analogue design from the bench to the bedside. We are just beginning to learn how targeted modifications of the insulin molecule can fine-tune both its own properties and the downstream signaling functions of the insulin receptor.”
That announcement, and the cutting-edge work Weiss is helping shepherd through Thermalin, has taken the researcher a long way from this first trip to Kenya, and an even longer way toward making insulin an exciting and worthwhile field of study.
“When I was a student at Harvard, and I told my first department chair my ideas about improving insulin, he said ‘We know everything about insulin,’” Weiss says. “Because insulin seemed like an ‘old’ protein, he told me I’d limit my career in academic medicine if I concentrated on insulin. Now I’m involved in work I find completely energizing. It’s work I think can make a difference in people’s lives.”
