New treatment could delay onset of type 1 diabetes
A research team led by QSI RENU member Jacqueline Burke is advancing a therapeutic that could significantly delay the progression of type 1 diabetes.
In this condition, immune cells attack the cells that produce insulin in the pancreas. As more cells die, blood sugar regulation stops — forcing patients to rely on daily insulin injections for the rest of their lives.
Although insulin shots keep these patients alive, they are still subject to large fluctuations in their blood sugar levels. Low blood glucose is associated with brain fog that can lead to serious accidents, and high blood glucose is directly linked to microvascular complications, including amputation and blindness, later in life.
“We are not simply treating symptoms. We are targeting the underlying immune dysregulation that causes the disease in the first place — and doing so in a way that is precise, durable, and clinically practical,” said Burke, a Research Assistant Professor of Biomedical Engineering at Northwestern University. “In mouse models, we’ve shown that we can delay the onset of symptomatic type 1 diabetes.”
The research builds on work published in Nature Nanotechnology in January 2022, which showed that a targeted nanotherapy containing the immunosuppressant drug rapamycin prevented rejection in mice that had received islet transplants to treat their diabetes. Pancreatic islets control insulin production when blood sugar levels change, so islet transplantation is considered a potential cure for type 1 diabetes. However, transplantation comes with a host of issues related to the immune system rejecting the new islets, as well as complications and side effects related to taking large, untargeted doses of immunosuppressants.
In their current research, Burke and her team, including Biomedical Engineering PhD candidate Natalie Klug, are using the same rapamycin-based therapy to combat the disease at an earlier stage, before islet transplantation is necessary.
Burke emphasized it is key to intervene early, before irreversible tissue damage occurs. Type 1 diabetes onset is asymptomatic at the early stages, so testing is critical to find patients that would benefit from treatment.
High-risk populations include children with relatives with type 1 diabetes. A blood screening can be done at the doctor’s office or via Type 1 Diabetes TrialNet, which provides in-home or lab test kits.
Burke is also the Chief Scientific Officer of SNC Therapeutics, Inc., a spinout company from Northwestern that was awarded a Small Business Technology Transfer (STTR) grant from the National Institutes of Health this summer to assist in translating the therapy toward use in humans. Delaying the onset of type 1 diabetes is a new area of therapeutic focus for the startup company.
The STTR grant is supporting studies to optimize the dosing of the novel nanotherapy in mouse models of type 1 diabetes. This work will be conducted by Burke’s team at Northwestern, and SNC Therapeutics will lead a second aim of the project to scale up the manufacturing protocols for the therapy using Good Laboratory Practices (GLP).
In addition to the STTR grant, the researchers have received funding from Breakthrough T1D to support their efforts and are conducting large-animal studies in collaboration with the University of Pennsylvania.
For Burke, this work is personal.
“My diagnosis with type 1 diabetes at age nine changed the trajectory of my life and my family’s life,” Burke said. “My parents had to quickly learn how to manage the disease, and that was both emotionally and financially challenging. I had to grow up fast.
“The possibility of pressing pause on the autoimmune destruction that drives this disease — of giving children just a few more years of childhood — is deeply personal to me. After many years in the lab, now with the STTR grant, we are on a path to clinical translation.”
Editor’s note: Intellectual property associated with the targeted nanotherapy is subject to an exclusive license between Northwestern and SNC Therapeutics. Burke and Northwestern University have financial interests (equity) in SNC Therapeutics.