Pathways to Stop Type 1 Diabetes: A Look Forward
By Anna Brooks
On the search for a type 1 diabetes cure, scientists are experimenting with how to engineer beta cells to survive immune system attacks. At the American Diabetes Association’s 83rd Scientific Sessions in San Diego, experts shared early research findings and where we are on the path to stopping type 1 diabetes.
Researchers, advocates, and patients have long searched for a cure for type 1 diabetes, a chronic autoimmune condition in which the immune system destroys insulin-producing beta cells of the pancreas.
Right now, the closest thing to a cure is a pancreas transplant or the transplantation of beta cells from deceased donors. Both options come with major caveats, such as the limited number of pancreatic organ donors, how complicated it is to protect transplanted beta cells, and the need for long-term immunosuppressive medication.
“To reach the true control for glucose that patients need, we need to find a cure,” said Judith Agudo, principal investigator at the Dana-Farber Cancer Institute. “And a true cure comes from getting back what's missing – the missing beta cells.”
Agudo was one of a handful of experts who spoke at the ADA's Scientific Sessions and shared what they’re working on to crack the beta cell code and other pathways to stop type 1 diabetes.
Engineering super-strong beta cells
In type 1 diabetes, the immune system identifies beta cells as foreign. This triggers T-cells (which normally help protect the body from infection) to attack. One strategy for dealing with this is taking medication that lowers the body’s immune response.
The issue here is that suppressing the immune system makes the body more vulnerable to infection and cancer. People with diabetes are already at a higher risk for developing infections and cancer, so long-term immunosuppression comes with additional risks.
Agudo has been studying model T-cells she created called Jedi T-cells, which enable her to study the immune system’s attack on beta cells. Through her research, she noticed that though many cells were targeted by Jedi T-cells, some were able to survive.
“We learn from nature, from cells that are able to escape from an immune attack,” she said. “It tells us this is a healthy, insulin-producing beta cell that’s coping with a strong T-cell attack.”
While the mechanism behind why some beta cells can resist a T-cell onslaught is unknown, Agudo said uncovering this could allow scientists to engineer super strong beta cells that can be transplanted into patients and survive without the need for drugs that compromise the immune system.
Cloaking beta cells
Another issue is protecting cells that have been transplanted. T-cells will identify and attack the transplanted cells just as it did with the original cells – so how do we keep the new cells safe?
Agudo explained that one option is hiding them. One strategy is called encapsulation, which provides transplanted cells with a physical barrier that prevents immune cells from reaching them. The downside here is the barrier can make the exchange of nutrients and oxygen harder, as well as prevent the insulin the cells create from getting into the blood.
Other research suggests an “immune cloaking” strategy where islets are engineered to hide from or be unrecognized by immune cells that would normally target them as foreign objects.
“They become invisible, hide in plain sight, and now they can survive,” Agudo said.
Using gut bacteria as a vaccine
Evidence from studies suggests that the gut microbiome is a key component in the development of type 1 diabetes.
Aleksandar Kostic, assistant professor of microbiology at Harvard Medical School and investigator at the Joslin Diabetes Center, discussed his research around using microbial antigens (invading microbes or foreign substances) to develop a vaccine for type 1 diabetes.
Existing research supports the idea of vaccines against viruses that live in the digestive tract like Coxsackievirus B, which is thought to be a factor in developing type 1 diabetes. Recent animal studies have also been investigating a Salmonella-based vaccine to prevent and maybe even reverse diabetes. Kostic’s research has focused on vaccinating against another microbial antigen called poly-N-acetyl glucosamine, which may lead to protection against the condition.
“We’ve started developing this as therapy for type 1 diabetes,” Kostic said. “We’re finding vaccination with this antigen can halt diabetes in mice.”
Researchers like Kostic and Agudo are part of the ADA’s Pathway to Stop Diabetes program, which provides scientists with grants and resources to accelerate and transform diabetes research.
“It may sound like science fiction but it is not, it’s happening,” Agudo said. “We are at the very beginning, but it’s really an exciting moment.”
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