Insulete Co-founder on Hopes, Challenges for Diabetes Gene Therapy

Xconomy Wisconsin — 

[Editor’s note: This is part of a series of stories on physicians at the University of Wisconsin Hospital and Clinics who have become full- or part-time entrepreneurs.]

For almost 35 years Hans Sollinger has been searching for ways to combat Type 1 diabetes, a chronic and potentially deadly disease in which a patient’s immune system destroys the insulin-producing cells of his pancreas.

Sollinger attended graduate and medical school in his native Germany before moving to the U.S. in 1975 to do research and a surgical residency at the University of Wisconsin Hospital and Clinics, where he continues to work as a transplant surgeon, professor, and researcher.

He says that by the time he completed his residency in 1980, he knew he wanted to find a way to help patients with Type 1 diabetes—which had claimed the life of his adoptive brother, Max, five years earlier—live longer, healthier lives.

“For a surgeon, the obvious thing was pancreas transplantation,” he says. “That’s still the only way to cure diabetes.”

So in 1982, Sollinger began performing pancreas transplants. By 1995, he says he had performed about 500 of the procedures, some of which also involved a kidney transplant.

However, Sollinger says, “Doing a few pancreas transplants doesn’t make a dent in the disease.” Indeed, 1.25 million Americans currently have Type 1 diabetes, and 40,000 new cases are diagnosed annually, according to the Juvenile Diabetes Research Foundation. Yet only about 1,200 of them receive pancreas transplants each year, because the risks and costs (upwards of $200,000) associated with the surgery and the difficulty of finding donor organs. Sollinger envisioned a treatment that would be accessible to a much larger population than pancreas transplants. “I felt that perhaps gene therapy would be the way to go,” he says.

While the promise of gene therapy is vast, the practice has a long history of failure, particularly at the human-trial stage. Just a few gene therapy treatments have been approved in Asia and Europe, and none have reached the market in the U.S. However, that could reportedly change as soon as next year.

Sollinger acknowledges that going the gene therapy route was “risky” and perhaps somewhat “naïve,” but he believed it was the direction in which the scientific world was headed.

In 2004, Sollinger co-founded Insulete—the name is a portmanteau of “insulin” and “obsolete”—a Madison, WI-based startup that is seeking to commercialize a gene therapy designed to coax a patient’s liver cells into producing insulin. The hope is that the liver could take up the work of the damaged pancreas, sparing patients from having to inject themselves with insulin multiple times a day to regulate their blood glucose levels, Sollinger says.

From 2010 to 2014, Insulete performed experiments in which researchers injected diabetic rodents with a DNA sequence patented by the company, Sollinger says. The investigators then monitored the animals to determine how long they were able to control their glucose levels, he adds. Sollinger says some of the animals went as long as 15 months with no decline in insulin production.

Now, the company plans to progress to experiments on larger animals. Sollinger says that Insulete is preparing a clinical trial in diabetic dogs, with plans to start testing the gene therapy in five or six canines later this year. The startup’s collaborators include Généthon, a French research organization whose mission is to advance gene therapy treatments, and the UW School of Veterinary Medicine.

“Dogs have almost the identical Type 1 diabetes as [humans] do,” Sollinger says. “The experts consider diabetic dogs as the perfect preclinical model. Also, the experts say if we can get the insulin production in these dogs with gene therapy and are successful, that we are over the major hurdle.”

Sollinger’s closest collaborator on the project to date is Insulete chief scientist Tausif Alam. Sollinger recruited Alam to the UW from the University of Texas Southwestern Medical Center more than 20 years ago, and the two worked closely together for years prior to Insulete’s launch.

Around the time that Sollinger realized pancreas transplants weren’t going to be the way to make a major impact in how Type 1 diabetes is treated, he created a list of criteria that any new treatment must meet.

“The cure has to be available for every diabetic,” he says. “The cure has to be affordable, and simple: It cannot be associated with a major operative procedure. And the cure cannot be associated with the patient having to take concomitant drugs, such as immunosuppressants, which have significant side effects.”

To create their would-be cure, Alam, Sollinger, and their team constructed tiny “minicircles” of DNA that a combine a gene for insulin with a sequence that switches the insulin gene on when glucose levels rise. (The researchers patented that so-called glucose-inducible response element with help from the Wisconsin Alumni Research Foundation.)

Another step was deciding which organ would be the best to target with the therapy. Sollinger says that the liver made the most sense because it shares a number of enzymes with the pancreas, and the two organs develop from the same part of the embryo. What’s more, he says, “it’s known in gene therapy that the liver is an organ that is very receptive to taking up genes.”

“That has been a very good choice,” he says. “As the science progressed, everybody said, ‘Oh yeah, [the liver] is the right way to do it, obviously.’ We don’t have a lot of competitors, but the people who are doing it are using the liver as a target organ.”

Sollinger says some of the researchers around the world working to develop therapies similar to Insulete’s include Roy Calne at the National University of Singapore, Matthias Elsner at Hannover Medical School, Ann Simpson at the University of Technology Sydney, and Peter Thule at Emory University. Another leading researcher is Stanford University’s Maria Grazia Roncarolo.

Insulete, which earlier this year raised $300,000 from investors and brought on Jay Handy—himself a diabetic—to serve as CEO, isn’t quite sure “what the end game will look like” in terms of commercialization, Sollinger says. He says that being acquired by a big drug company is one future possibility, but that for now the startup is just trying to put one foot in front of the other.

“The burden of proof is on us,” he says. “We have had discussions with several large pharma firms who have animal healthcare subsidiaries, and they are very interested. But we have to get the dogs cured first.”

Of course the real question is whether Insulete’s treatment can cure humans without dangerous side effects, and numerous once-promising gene therapies have failed when they’ve reached that test. For his part, Sollinger says that gene therapy will “dominate medicine” over the next 20 years. Only time and data will tell if his prediction proves to be right.