Designing an On-and-Off Switch for Insulin

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JDRF glucose control therapy research

Calibr, a biomedical research center sees promising data with its glucose-responsive insulin designs

JDRF-supported Calibr, which stands for California Institute for Biomedical Research, is a unique interdisciplinary institute poised to create insulins that can control glucose better for people living with type 1 diabetes (T1D). “We are about a year into the project, and we are witnessing intriguing initial data that suggests we can prove the concept in the next three years in animal models of diabetes,” said Matthew Tremblay, Ph.D., ‎Vice President, Strategic Alliances at Calibr.

“The point isn’t just to look at the glucose challenge like we do in mice. It’s to think of all the many small glucose challenges when people eat, live and sleep,” said Dr. Tremblay.

To learn more about Calibr’s glucose-responsive insulin (GRI) design, watch this brief video.

The Switch

Calibr is developing a new GRI with a novel antibody platform. Their design will create a switch for a person with T1D that “turns on” at high concentration of glucose and it can “turn off” at low concentration of glucose. It is also designed to remain dormant until it is activated. This glucose responsiveness is designed to closely mimic the natural insulin release in people without T1D, a process that has involved regulating the release of the right amount of insulin for any given glucose concentration. “Our design also may include a long-acting feature which means it requires probably very low frequency of injection, that’s also beneficial,” said Feng Wang, Ph.D., Principal Investigator, Protein Chemistry at Calibr.

Real Life

Another exciting aspect of Calibr’s insulins is the possibility of maintaining glucose levels in a tighter range; Tremblay and his team are seeing fewer highs, and expect fewer and less severe rebound lows compared with today’s analog insulins in animal models. The goal is to tightly control the fluctuations in glucose that are normally experienced in T1D.  “We are mimicking what a patient would be experiencing in real life, not these very exaggerated glucose changes but small changes after meals and dips during the night when the body is using stored glucose,” said Dr. Tremblay. “Finally, we have to also consider the safety of the molecule, so efficacy and safety studies will be done,” according to Dr. Wang.

Why it matters

Calibr’s glucose-responsive insulin could keep blood-glucose levels within a tighter range for people with type 1 diabetes. This may help people avoid both acute and chronic adverse risks. Acute situations are life-threatening, and daily fluctuations in glucose levels can cause long-term complications.