Thanks to a new three-year, $1 million grant, a group of researchers at Case Western Reserve University are continuing to develop and test a form of glucose-responsive insulin that may someday be able to reduce the risk of dangerous hypoglycemic episodes in people with type 1 diabetes.
The insulin is being developed in the lab of Dr. Michael Weiss, the chairman of the department of biochemistry at Case Western Reserve University. He’s been studying insulin for some 35 years and even spun out a company, Thermalin Diabetes, in 2009 to commercialize a portfolio of insulin analogs he’d developed. If these new smart insulin analogs demonstrate in animal studies what he thinks they will, they could eventually become part of Thermalin’s portfolio too.
Weiss and his research team have engineered a kind of injectable insulin that can detect when levels of glucose in the body are too high or too low, and release itself into the bloodstream accordingly.
Insulin, as a naturally occurring hormone, helps the body convert food into energy and maintain regular levels of sugar in the blood. In people with type 1 diabetes, the body attacks its own insulin-producing cells in the pancreas and leaves these patients prone to high levels of blood sugar that eventually results in complications if it’s not controlled. So to avoid hyperglycemia, patients take insulin, most often through injection, and usually with meals.
But with that comes the risk of injecting too much insulin, which could result in blood sugar levels that are too low to the point of causing headaches, shakiness and sometimes even more serious episodes of fainting or seizures.
“It’s an unfortunate and anxiety-provoking, and sometimes dangerous part of the treatment of type 1 diabetes, and it’s a limiting factor in how aggressive treatment is,” Weiss said. “There’s a catch-22 that we’re trying to circumvent. It’s that the more successful a patient is in preventing the upward excursion (of blood sugar), the higher the risk they are at for the downward excursion, which cause these hypoglycemic episodes.”
Weiss and his research team are redesigning part of the insulin molecule so that it “sticks” to the inside of the skin until the presence of a certain concentration of glucose in the blood signals it to be released. They’re doing that by exploiting lectins that are present under the skin, which bind to carbohydrate-modified proteins. By redesigning the insulin analog to include specially tailored carbohydrates that bind to the lectins, the insulin becomes “sticky,” as Weiss put it, when blood glucose is low and prevents too much insulin from being absorbed and causes a hypoglycemic episode.
“If we can do that, then patients can be more aggressive in treating their ‘highs’ because they don’t have to worry about the lows,” Weiss said.
It may sound futuristic, but this actually isn’t a new concept. In fact, it dates back as far as a study published in Science in 1979, Weiss said, in which researchers treated rodents with insulin and a plant lectin, and demonstrated the principle of glucose-responsive insulin. The lectin they used, however, was not safe for use in humans.
An MIT spinout called SmartCells spent several years working on improving a similar kind of technology before being sold to Merck in 2010. Nothing has been heard about the technology since then. Weiss’ team’s approach, he said, is different because of the precise design of the insulin and the fact that they’re exploiting the endogenous human lectins under the skin rather than injecting lectins along with the insulin.
With the three-year, nearly $1 million grant from The Leona M. and Harry B. Helmsley Charitable Trust’s type 1 diabetes program, the team will conduct proof of principle tests in animals — initially rats and mice, eventually moving the final candidates into pigs. If these tests prove successful, the new analogs would likely be licensed and developed through Thermalin as well.
“Glucose-sensitive insulin is of great interest to the type 1 diabetes community because it will help patients who struggle with hypoglycemia to manage their blood sugar better and with less worry,” Thermalin CEO Richard Berenson said in a prepared statement. JDRF, a global type 1 diabetes foundation, has even put together an open innovation looking for ways to develop such an insulin.
“We see intelligent insulin as a perfect complement and addition to our product strategy,” Berenson said.