Innovation Takes on Hypoglycemia

Posted on: June 5, 2018

Protomer Technologies in Pasadena, CA, just nabbed first place in T1D Exchange’s 2018 Diabetes Innovation Challenge for its concept of a “smart glucagon” that would, in essence, cure severe hypoglycemia.

Protomer Technologies’ Jack Hale (left) and Alborz Mahdavi (right) with Dana Ball, Executive Director of T1D Exchange.

As individuals with type 1 diabetes know, the pancreas normally releases a peptide hormone called glucagon, which tells the liver to start making glucose. However, individuals with type 1 diabetes mysteriously cannot release glucagon. Worse, those who have had type 1 for longer periods of time can lose their ability to sense episodes of low blood sugar. This hypoglycemic unawareness—added to the troubles of glucagon release—equals a very high risk of developing severe hypoglycemia, which can be a cause of sudden death in both individuals with and without type 1 diabetes.

Protomer CEO and chemical engineer Alborz Mahdavi set out to tackle the challenge. While working in the laboratory of David Tirrell (the current provost at Caltech) in the early 2010s, Mahdavi began toying with artificial amino acids, which are the Lego® blocks that form to make peptides and proteins. His student thesis won a prize but more importantly inspired the idea of engineering peptide hormones to turn on or off in response to glucose.

A glucose-responsive glucagon would “eliminate severe hypoglycemia and also allow individuals with type 1 diabetes to be a little bit more aggressive with their insulin injections,” says Mahdavi. “We basically fell in the love with the concept.”

He references the “dead in bed” syndrome, thought to be due to hypoglycemia and affecting patients under the age of 40 years. “It is unbelievable that young people are dying in their sleep because of hypoglycemia,” Mahdavi says. “If one could develop a drug to eliminate that, even if it is a moon shot, one should take it.”

He did, and he has a significant advantage. While a graduate student at Caltech, Mahdavi began working on a “smart insulin.” He engineered the peptide hormone to activate only when blood glucose started to rise. Inject it once daily and let it circulate; the insulin could anticipate an episode of hyperglycemia. Once glucose levels returned to normal, the insulin would stop working, but still remained in the body, waiting for the next blood sugar high.

The idea won Mahdavi a Challenge contest in 2013, sponsored by JDRF. The prize money led to the launch of Protomer. For two years, Mahdavi researched glucose-responsive insulin. In 2016, he scored a $1.5M grant, sponsored by JDRF and Sanofi, focused specifically on glucose-responsive insulins. That technology is now advancing toward pre-clinical development.

Meanwhile, Mahdavi and his team member Jack Hale, a stem cell scientist and Protomer’s first employee, are focusing on glucagon. Through his contacts at JDRF, Mahdavi stumbled onto T1D Exchange and decided to enter its 2018 Diabetes Innovation Challenge.

“Honestly, we were going into competition thinking already we won just because we were finalists,” he says. “What T1D Exchange does very well is provide a platform for companies to be able to connect with important players in the field.”

Indeed. Stay tuned for how the company fares.