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Research spotlight – immunotherapies for Type 1 diabetes

Type 1 diabetes happens when your immune system attacks the insulin-producing cells in their pancreas, leaving you unable to make the insulin you need to live.

The current treatment for Type 1 diabetes involves replacing the insulin that your pancreas can’t make. This is done through insulin injections or pumps.

But this doesn't treat the cause of Type 1 diabetes – an immune attack. This is what immunotherapies are aiming to do.

 

Research in the lab is helping to develop new treatments

The state of play

It was our scientists, led by Professor Gianfranco Bottazzo, that were at the heart of a huge discovery back in 1979. They found that Type 1 diabetes results from an immune attack on the cells in the pancreas which make insulin, called beta cells.

Since then, we’ve built a more detailed picture of what happens to the immune system in people with Type 1 diabetes. And our scientists are now using this knowledge to develop treatments that target it. This is called immunotherapy.

Immunotherapies are already being tested in trials, to work out if they’re safe and effective. But there aren’t yet any treatments available outside of a research setting. We’re supporting the research that will hopefully get us there.

In the future, it could mean we can stop people at risk of Type 1 diabetes from ever developing the condition, and slow the attack in those already diagnosed.

A closer look at the immune system

To understand how immunotherapies work we need to take a look at how Type 1 diabetes develops. Our immune system is normally made up of a balance of different types of immune cells, which work together to protect us from illnesses.

A particular group of immune cells – called ‘killer’ T cells – are the assassins of the immune system. They recognise and destroy harmful bacteria or viruses. At the other end of the scale sit regulatory T cells, or Tregs. They police the immune system and keep it in check by turning off killer T cells when they’re no longer needed.

But in Type 1 diabetes, killer T cells mistakenly target our own healthy beta cells. Their population then grows and they outnumber the Tregs. The causes the scale to tip and the destruction of beta cells begins.

Although killer T cells have emerged as the primary culprits in Type 1 diabetes, they don’t act alone. Another type of immune cell – called B cells – are also involved. They don’t directly attack the pancreas, but may play a role in ‘talking’ to T cells and triggering their attack.

B cells also produce proteins – known as autoantibodies – which tell us that something is going wrong with the immune system. They signal that damage is being done even decades before someone develops Type 1 diabetes.

Stopping the immune attack

Through understanding more about the different immune cells involved in Type 1 diabetes, researchers have begun to work out how to target these cells and stop an attack.

Immunotherapies can work to:

  • Target and switch off B or T cells, so they won’t destroy beta cells
  • Boost Tregs, so they can better fight the cells trying to do harm
  • Retrain the immune system to tolerate specific proteins that it normally reacts to in Type 1 diabetes. This is similar to treatments for peanut allergies, where people take small doses of peanuts to help their immune system recognise and tolerate it.

If successful immunotherapies could be used at different points. They could help people at high risk of Type 1 diabetes, by delaying the onset of the condition or by preventing it entirely.

They could also be used to stop Type 1 diabetes in its tracks in those who are newly diagnosed. We know that when someone’s first diagnosed they can still have up to 40 per cent of their insulin-producing cells remaining. Over the next few months or years they are gradually destroyed.

But in the future, immunotherapies could protect these remaining cells, helping people to carry on making some of their own insulin. This would make blood glucose levels easier to manage and could reduce your risk of serious complications down the line.

What we're doing

We’re funding over £6.2 million of research projects right now to unravel the immune attack and support the development of immunotherapies.

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This includes:

  • Professor Marelli-Berg, who’s testing if an existing drug could help Tregs work better and protect beta cells.
  • Professor Susan Wong is looking at a protein found on B cells to figure out whether changes in its levels could play a role in the Type 1 immune attack.
  • Dr Parth Nardendran is trying to identify the exact regions on beta cells that killer T cells recognise, which could help develop new immunotherapies.

The Type 1 diabetes immunotherapy consortium

To take us closer to making immunotherapies a reality, we invested £2.8 million into the Type 1 diabetes Immunotherapy Consortium (T1D UK), in partnership with JDRF and with support from Tesco. It brings together researchers from across the UK to develop and test new immunotherapies.

The T1D UK hopes to speed up progress and make sure new therapies reach people with and at risk of Type 1 diabetes as soon as possible.

There are three main parts to the T1D UK:

  • Professor Colin Dayan at Cardiff University is setting up a network of 15 research teams across the UK. This will increase the UK’s ability to carry out trials of immunotherapies and allow many more people with Type 1 diabetes to take part.
  • Dr Tim Tree at King’s College London is leading specialist labs to look at the effectiveness of immunotherapies. He’s studying samples from people who’ve taken part in Type 1 immunotherapy trials to examine their immune cells. He wants to understand in detail how the treatments work and share this knowledge with other scientists, to help improve future treatments and trials.
  • Professor Des Johnston at Imperial College London is building a database of information and biological samples from people who have been recently diagnosed with Type 1 diabetes (called ADDRESS-2). The database helps recruit people to immunotherapy trials and learn about the characteristics of people newly diagnosed.

The immunotherapy consortium is helping us lay the foundation needed to propel immunotherapy research forward and could lead to life-changing treatments to stop Type 1 diabetes in its tracks.

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