July 27, 2020  Print

A new WIMR-led study, published on the cover of Diabetes, has demonstrated how a combination of treatments could improve outcomes for islet transplant recipients.

Islet transplantation involves taking healthy pancreatic or ‘islet’ cells from a donor and transplanting them into a recipient’s pancreas. It is an emerging treatment for type 1 diabetes, which is an autoimmune condition where the body’s immune system destroys the insulin-producing pancreatic cells.

Although islet transplantation is effective, patients who receive a transplant must remain on immunosuppressive medication to reduce the risk of graft rejection.
Previous research in animal models has identified two therapies that could reduce the length of immunosuppressant treatment, and reduce the likelihood of graft rejection: recombinant human interleukin-2 (IL-2), a protein involved in the body’s immune response, and rapamycin, an immunosuppressant.

WIMR researchers investigated whether low doses of these therapies could improve outcomes for islet transplant recipients. The team found that the combination of the two treatments increased the likelihood of graft survival, and decreased the likelihood of rejection in mouse models.

Co-lead author Dr Min Hu said, “Our study is the first to demonstrate the effectiveness of IL-2 and rapamycin in increasing the likelihood of graft survival of human islet transplants in a mouse model. 
“We tested the treatments individually, but found that only the combination of the two produced an immune response that could improve the likelihood of transplant survival.”

The combination of IL-2 and rapamycin increased the number of CD4+CD25+FOXP3+ regulatory T-cells (Tregs), which is associated with graft survival. The research team hope to conduct further studies to explore how the combination of treatments could benefit patients.

Co-lead author and transplant clinician Professor Philip O’Connell said, “Islet transplantation can significantly reduce the burden of disease for people with type 1 diabetes, particularly those who suffer from hypoglycaemia unawareness – a condition where an individual’s blood sugar drops to dangerously low levels without warning.

“However, we also recognise that there can be complications and side effects to transplantation that we hope to minimise.

“Rapamycin is administered to some islet transplant recipients, and IL-2 is approved for clinical use. While more studies are necessary to translate our findings into human clinical trials, it is promising to see positive results from two treatments that already have clinical approval.

“With further research, we aim to develop a treatment regimen that can reduce the need for long-term immunosuppression, and increase the likelihood of transplant survival.

“Ultimately, our research aims to improve the quality of life of islet transplant recipients.”
The research was published in Diabetes