Root causes

Combination therapy could help protect insulin-producing beta cells

Dr Danijela Tatovic’s Root Causes Programme Grant project

Dr Danijela Tatovic

Dr Danijela Tatovic is a clinical research fellow at Cardiff University who designs early phase clinical trials, which are an important step towards taking science from the lab bench into the clinic. In this Grand Challenge research project, Dr Tatovic will test a combination of two therapies, both already licensed to treat other autoimmune conditions, to see if together, they can help protect surviving beta cells and delay progression of type 1.

Background to the research project

Type 1 diabetes occurs when a person’s own immune system mistakenly attacks insulin-producing beta cells in the pancreas. This process is known as an autoimmune response and in people at risk of type 1, it begins long before the symptoms of diabetes appear.

New therapies that help to control these autoimmune responses and prevent or slow the attack on beta cells are showing real promise. One medicine, abatacept helps to stop ‘bad’ immune cells from attacking the beta cells. However, the drug also dampens down ‘good’ immune cells that naturally control the autoimmune response. So, it’s important we have the right balance of them.

Dr Danijela Tatovic’s research is exploring how to overcome this problem. So far, she has shown that in mice with type 1 combining abatacept with another medicine, called IL-2, can help to keep the right balance of immune cells, so beta cells are better protected from the ‘bad’ ones.

What will Dr Danijela Tatovic do in this project?

Now Dr Tatovic’s’s team wants to understand whether a combination of abatacept and IL-2 works in people with type 1 and to find out what dose and timings of the medicines work best.

The researchers will run a small clinical trial where one group of people with type 1 will receive abatacept over two months, boosted with IL-2. Another group will receive abatacept alone.

To understand more about how the immune cells respond to the medication, the researchers will use state-of-the-art methods and equipment to track where the immune cells are in the body, and when and how they are doing their job.

Dr Tatovic’s is also joining forces with other experts, who will  sophisticated mathematical models to analyse the data they collect and to predict which doses of each treatment is likely to be most successful in combination.

How will this research help people with type 1 diabetes?

Knowing which doses of the combination of drugs are most effective at preserving beta cells will allow the researchers to design a larger clinical trial, involving more people. The next trial will help them to find out whether the therapy can protect beta cells from destruction and prevent or slow progress of type 1 diabetes. In future, it could mean that people at risk of type 1 can be treated before their beta cells have been destroyed, to try to delay or prevent the condition from developing. While disrupting the immune attack in people who’ve just been diagnosed with type 1 could help to keep more of their surviving beta cells alive, so they can make some of their own insulin for longer.

Dr Danijela Tatovic said:

“As a clinical diabetologist, I witness the struggle that people with type 1 diabetes go through on a daily basis to achieve optimal control of their blood sugars. This is changing. We are on the cusp of making fundamental difference to the treatment of type 1 diabetes, from burdensome insulin replacement to preserving a person’s own insulin. I am delighted and very grateful to the Type 1 Diabetes Grand Challenge.”