University of Alberta’s 13 projects get nearly $10 million support
A University of Alberta research team is testing graft materials that deliver anti-rejection drugs directly to transplanted insulin-producing cells with the goal of making transplants safer and more accessible for people with diabetes.
The project is one of 13 U of A research proposals funded by new Canadian Institutes of Health Research grants worth nearly $10 million (see full list of projects below).
“We’re looking at reducing the reliance on systemic immunosuppression drugs and keeping them localized to just the cells that are providing the glucose control instead of the whole body,” explains Andrew Pepper, assistant professor of surgery and Canada Research Chair in Cell Therapies for Diabetes.
“We think that will reduce the side-effects, reduce the risk and increase the patient population that could benefit from a life-changing beta cell replacement therapy,” says Pepper, who co-leads the project with Greg Korbutt, scientific director of the Alberta Cell Therapy Manufacturing facility.
An estimated 300,000 Canadians have Type 1, or insulin-dependent, diabetes. In 2000, a U of A team launched the groundbreaking Edmonton Protocol — which has so far transplanted insulin-producing beta cells into the livers of 255 patients whose diabetes could not be well controlled with insulin injections.
Those patients must take lifelong anti-rejection drugs, which can lead to infection, kidney damage and even cancer. The transplant program relies on donated organs, with each recipient needing cells from two or three donors, so the number of patients who can be treated is limited.
“We know that in the early post-transplant period, within hours to days, we lose up to 70 per cent of the cells,” says Pepper. “If we can help the cells to survive longer then hopefully we can use just one pancreas per recipient.”
Pepper’s research team will graft beta cells under the skin with bubble-like microparticles developed by research associate and biomaterials expert Purushothaman Kuppan. They slowly release medication to prevent post-transplant inflammation, promote insulin secretion and encourage cell survival. The team will first test the grafts on mice and pigs and then, if results continue to be positive, will make plans for a human clinical trial.
“We have been able to use a fraction of the dose (of anti-rejection medication) in animal models to date, with the cells surviving for hundreds of days,” says Pepper. “The drugs are only present for about a month because the bubbles pop over time.”
Pepper is hopeful the method would be effective at protecting donor beta cells or beta cells derived from the patient’s own stem cells, another advance being developed at U of A.
The project will receive $1,082,476 over five years from CIHR, building on work previously supported by the Juvenile Diabetes Research Fund and Alberta Innovates. Pepper and Korbutt are members of the Alberta Diabetes Institute.