Australian researchers have initiated the world's first human trial of a potentially revolutionary immunotherapy designed to treat the underlying cause of Type 1 diabetes by reprogramming the immune system.
Five participants have already received doses of the experimental drug ASITI-201 at the Translational Research Institute's Clinical Research Facility at Brisbane's Princess Alexandra Hospital. The trial represents a significant milestone in the 25-year research journey led by Professor Ranjeny Thomas from The University of Queensland's Frazer Institute.
Novel Approach to Autoimmune Intervention
Type 1 diabetes, affecting more than 130,000 Australians, occurs when the immune system mistakenly attacks and destroys insulin-producing beta cells in the pancreas. Current standard treatment is limited to insulin replacement therapy.
"In people with Type 1 diabetes, the immune system starts to recognise pancreatic cells as something it needs to attack, and right now the only available treatment is insulin replacement," explained Professor Thomas. "We've taken a new approach and developed ASITI-201 using a protein from the pancreas, along with vitamin D to calm the immune response."
The drug, administered as a subcutaneous injection, combines fragments of a protein found in pancreatic beta cells with vitamin D to modulate the immune response. This approach aims to retrain the immune system to stop attacking insulin-producing cells.
"This therapy is really trying to get to the root cause of the autoimmune disease," Professor Thomas said. The treatment has already demonstrated success in controlling the disease in preclinical mouse models.
Trial Design and Objectives
The first-in-human trial will enroll 36 participants to evaluate the safety profile of ASITI-201 while also assessing its impact on immune function and glucose tolerance. Three different doses will be tested against a placebo in a blinded study design.
Dr. Aakansha Zala, lead investigator and endocrinologist at the Princess Alexandra Hospital, outlined the primary goal: "We will be looking at whether the drug changes the immune system in the way that we anticipate."
The researchers are recruiting adults over 18 who have been diagnosed with Type 1 diabetes within the past five years. Funding is available to support travel costs for eligible participants living outside Brisbane.
Patient Perspective
Among the first participants is Caecilie Wickstroem Giralde, a 36-year-old mother of two who was diagnosed with Type 1 diabetes in October 2023 after experiencing gestational diabetes during her pregnancies.
"Multiple daily injections of insulin is so hard," Wickstroem Giralde said. "I will never get used to giving myself injections. I have to take a deep breath, close my eyes every time I have to do it."
She described how the condition impacts family life: "At dinner time, I'll take my insulin, I'll eat, we might muck around a little bit more than what we usually do, and my blood sugar will go low just as I'm about to put the kids to bed."
Dr. Zala emphasized that living with Type 1 diabetes is "exhausting" for many patients and can lead to serious complications including kidney disease, nerve damage, vision loss, and increased risk of cardiovascular events.
Potential Clinical Impact
If effective, ASITI-201 would initially be administered to newly diagnosed patients to preserve remaining pancreatic function and reduce insulin requirements. However, the researchers envision broader applications.
"If we can show that this drug is very safe and it does what we expect to calm the immune system, then that is an opportunity for us," Professor Thomas said. "Eventually, if screening programs can be developed to identify people at risk of developing Type 1 diabetes, it may be possible to prevent the progression of the disease altogether."
Professor Grant Brinkworth, Diabetes Australia's director of research, who is not involved in the trial, commented that the drug being tested could "fundamentally change" the lives of people diagnosed with Type 1 diabetes.
"If successful, this research could reduce or eliminate the need for people living with the condition to endure life-long daily insulin injections and lessen the risk of the health complications associated with living with diabetes," Professor Brinkworth said.
Development and Funding
The trial is funded by the Medical Research Future Fund via Australia's national biotech incubator CUREator, which helped establish spin-out company Liperate Therapeutics through UQ's commercialization company UniQuest.
The drug's preclinical development received substantial support, including $2.54 million from Breakthrough T1D (formerly JDRF) between 2003-2015 and $5.33 million from The Leona M. and Harry B. Helmsley Charitable Trust to complete preclinical development, safety studies, and manufacturing.
Dr. Ben Williams from the Helmsley Charitable Trust, the largest private funder dedicated to transforming the trajectory of Type 1 diabetes, acknowledged the significance of the milestone: "Bringing drug candidates from the laboratory into clinical testing is always a herculean effort."
Professor Thomas and her team are also developing a similar therapeutic approach for rheumatoid arthritis, suggesting potential broader applications of this immunotherapy platform for various autoimmune conditions.
Future trials, including studies involving children who typically experience faster progression to insulin dependence, are already being planned, pending results from this initial safety and mechanism study.
