Root causes

Does timing matter for therapies to prevent beta cell destruction?

Dr James Pearson’s Root Causes Programme Grant project

Dr James Pearson is a diabetes researcher at Cardiff University. This Grand Challenge project will allow him to test whether a new medicine, that slows the destruction of beta cells in people with type 1 diabetes, is more effective if administered at a particular time of day.

Background to the research project

Type 1 diabetes occurs when a person’s insulin-producing beta cells in the pancreas are destroyed mistakenly by the body’s own immune system. The error occurs, at least in part, because immune cells called Tregs that normally help prevent beta destruction, can’t do their job properly in people who develop type 1.

Medicines designed to help boost Tregs and protect beta cells from destruction are being tested in clinical trials with people who’ve recently been diagnosed with type 1. One of the medicines is a low dose of a protein called IL-2 that helps the population of Tregs grow and do their job effectively. However, although the trial results are promising, for some people, the medicine just doesn’t work.

Dr Pearson’s previous research tells us that the number of Tregs in a person’s blood follows a daily pattern, rising and falling during a single day. He’s also found that these cells can only do their job of policing the damaging immune responses at the root of type 1 at certain times of day. In mice, IL-2 protein is responsible for altering these time-of-day changes in Tregs. When the mice are given IL-2 at 7pm, their Tregs do a better job at preventing beta cell destruction than when the same dose is given at 7am.

What will Dr James Pearson do in this project?

Dr Pearson wants to find out whether the differences in Treg activity in the morning and evening can explain why some people with type 1 don’t benefit from the IL-2 therapy. He will explore when during the day Tregs get the biggest boost from the IL-2 in mice, and test whether IL-2 is more effective in the morning or evening at preventing or slowing type 1.

Dr Pearson will also study blood samples from people with type 1 to identify how the Treg activity varies between individuals. He will treat samples of people’s Tregs in the lab with IL-2 to see how it boosts the cells’ ability to control the immune cells that destroy beta cells.

How will this research help people with type 1 diabetes?

By looking closely at Treg cells in both mice and humans, Dr Pearson and his team will discover why Tregs behave differently at different times-of-day and the best time to give a promising new medicine to best boost Tregs, so they can to do their job better and help to fend off the immune attack in people with or at risk of type 1.

Dr Pearson’s research could mean that in future, IL-2 can be given to coincide with when the body’s cells are most responsive to the therapy. It may lead to a new clinical trial to test a time-of-day-specific low dose IL-2 for people with type 1 and those at high risk of developing the condition.

Dr James Pearson said:

“I am thrilled to receive this funding for our research which will expand our research group and move our research forward into clinical practice. This research will identify how immune cells vary over the course of the day but also how well they respond to therapy. This knowledge will enable us to improve the success of therapies for people with, and at risk of, type 1 diabetes by identifying when best to administer therapy.”