WisBusiness: Transplant expert devises novel therapeutic strategy for Type I diabetes

By Caroline Schneider

For WisBusiness.com

Dr. Hans Sollinger, founder of Insulete Inc. and professor of surgery at UW-Madison, has been performing pancreatic transplants for the treatment of Type I diabetes for decades. While the surgeries can be successful, they can also have several complications: costs are high, donors are hard to find and patients must endure immune-suppression after receiving the new pancreas. Sollinger knew years ago there had to be a better way to treat patients.

When Sollinger began to think about strategies for a better therapy, he had three goals. “The first was that the therapy has to be available for everybody. Second, it has to be simple with no major operation. Finally, the therapy has to be cheap,” said Sollinger.

More than 1 million Americans suffer from Type I diabetes. In patients with the disease, the pancreas does not produce insulin in response to glucose in food. Therefore, glucose cannot be utilized for energy, and patients suffer from abnormal blood glucose levels. In some cases, Type I diabetes can lead to heart disease, blindness and kidney failure.

Sollinger and his colleagues created Diatagene, a therapy that could prevent several of the common diabetes complications and that fits all three of his criteria. Diatagene is a small circle of DNA called a minicircle. In the DNA sequence, Sollinger placed the insulin gene and a patented glucose-inducible response element. With the elements together, the construct could recognize an increase in glucose and pump out insulin in response, just as normal pancreatic cells do.

Because they didn’t want insulin being produced anywhere in the body, Sollinger and his colleagues had to pick specific cells to target.

“If you look at your embryology book, the liver and pancreas are embryonically related. Also, liver is one of the few regenerating organs in the body. For our therapy, we need to get Diatagene into about 5 million cells. Even if cells were to die, it would be no problem. They would grow back. So, we picked the liver cell for our target cell,” explained Sollinger.

The next step was figuring out how to get the construct to the liver cells. To find a solution to this problem, Sollinger when back to his original criteria for the therapy.

“I maintained that the procedure had to be simple. So, we modified the minicircle so we could give it through an intravenous injection,” said Sollinger. “Here was the plan: the diabetic patient will get an injection of a solution that contained the minicircles. The minicircles will float to the liver, go into the liver cells, attach and function like a little pancreas.”

Once Sollinger had a strategy, the group began trying the therapy in animals. After administering the minicircle solution and giving the animal a dose of glucose (similar to a patient eating a meal), researchers measured levels of glucose and insulin in the animal’s blood. The glucose and insulin levels in the animals looked exactly as they would in patients without diabetes.

“When the lab researchers came into my office and showed me these data, I thought they were dreaming,” remarked Sollinger. “We had achieved perfect regulation.”

The results of these experiments enticed Sollinger to start Insulete Inc. The company name stands for “insulin obsolete,” since Sollinger hopes to make daily insulin injections, the only other current therapy for type I diabetes, unnecessary. Instead, his Diatagene treatment needs to be injected only once per month.

Insulete, Inc. currently has a staff of four members including Sollinger, Bill Checovich, Jonathan Fritz and Tausif Alam. They hope to complete studies of Diatagene in large animals by the middle of 2012 and move into phase I trials by the end of 2012 or early 2013. Sollinger estimates that they will grow to 15 or 20 employees within a year.

“There will actually be two markets,” Sollinger explained. “One will be addressed early, and that is the diabetic pet market. We will also, of course, focus on the human patients.”

Insulete Inc. was recently selected to present at November’s Early Stage Symposium. Through the symposium, he was looking to get the company name out into business and investor circles as the company was seeking $3 million in capital to support further animal studies, toxicology screening and phase I trials.

Sollinger points out that he and his colleagues have already spent about $4 million on the development of Diatagene through grants and other funding. He is excited to see the product move further through testing.

“This is not something we discovered yesterday,” said Sollinger. “This is 20 years of basic work.”

— Schneider is a graduate student in the UW-Madison Department of Life Sciences Communication.