Case Western Reserve University's School of Medicine has received a nearly $1 million grant from The Leona M. and Harry B. Helmsley Charitable Trust's Type 1 diabetes program.
The three-year award will support research on a rapid-acting, glucose-responsive insulin by biochemistry professor Michael A. Weiss, MD, PhD, MBA, an internationally recognized leader in insulin research for nearly a quarter century. Weiss will lead work on a form of insulin that detects when levels of the sugar-storing hormone may be too high or low, reducing the risk of hypoglycemia in diabetes patients. If the research is successful, this new type of insulin would most likely be developed through Cleveland-based Thermalin Diabetes LLC, a company Weiss founded in 2009.
The Intelligent Insulin Project
National Institutes of Health-sponsored clinical trials conducted by Case Western Reserve School of Medicine and others have established that long-term complications of Type I diabetes (T1D) -such as blindness and kidney failure-could be delayed or prevented by tightly controlling the concentration of glucose (sugar) in the blood. Such control is achieved by administering insulin-a hormone that instructs the body to remove sugar from the blood and store it for later release-with each meal to dampen the spikes in blood sugar that occur when the body digests carbohydrates.
But when too much insulin is given, the patient experiences a "low"-a hypoglycemic (low blood sugar) episode that can lead to confusion, anxiety, irritability and, with progressive severity, loss of consciousness, convulsions or even death. Preventing an insulin overdose is a challenge. Carbohydrate consumption frequently falls short of pre-meal estimates. Patients can also drive their blood sugar levels low by being more active than expected. When either of these things occur, the insulin dose that was given before a meal can turn out to be too large and the patient becomes hypoglycemic.
With current technologies, the risk of at least mild overdosing is very real. So patients frequently underdose and as a result fail to achieve tight blood sugar control. Surveys have indicated that better blood-sugar control from more aggressive insulin therapy would be achievable if new technologies could be developed to reduce the risk of hypoglycemia.
"We are now trying to invent new, more intelligent forms of the insulin molecule that reduce the risk of overdosing," Weiss said.
Weiss and his Case Western Reserve research team will redesign part of the insulin molecule so that it "knows" to stay at the injection site when blood sugar is low, thereby preventing the level from slipping further. This can, in principle, be accomplished by creating insulin analogs that stick inside the skin until the presence of glucose signals that it's time for the hormone to be released.
The injected insulin analog will be intrinsically sensitive to the concentration of glucose under the skin, so that that the insulin will enter the bloodstream only as needed.
"Glucose-sensitive insulin has attracted intense interest in the past," Weiss said. "We may have a novel solution that uses an entirely new mechanism and avoids the pitfalls confronted by other approaches."
Robert H. Miller, PhD, the university's vice president of research and technology management and Allen C. Holmes Professor of Neurological Diseases, said the development of smart therapies, such as the responsive insulin designed by Weiss, "is the culmination of a huge amount of basic research on the chemical structure of insulin as well as biology of diabetes. It demonstrates the power of linking the bench to business at CWRU."
The New York-based Helmsley Charitable Trust has rapidly become one of the largest private funders of T1D initiatives. The award to Case Western Reserve is part of the Helmsley T1D Program's Emerging Technology Initiative (ETI).
The goal of the ETI is to fund earlier stage projects focused on drugs, devices or therapies that will ease the burden of managing T1D and move them down the path towards commercialization. Along with Case Western Reserve, Helmsley has awarded grants totaling more than $6.5 million through this initiative to six other organizations.