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Research spotlight – retraining the immune system to fight Type 1 diabetes

If you have Type 1 diabetes, your immune system has attacked the insulin-producing beta cells in your pancreas. This means you can’t make enough of your own insulin, and need to replace it through injections or a pump. 

But insulin doesn't treat the underlying cause of Type 1 diabetes: an immune system attack. This is what new treatments – called immunotherapies – will be able to do, by reprogramming the immune system so that it no longer destroys beta cells. In the future, they could stop Type 1 diabetes in its tracks or prevent the condition entirely.

Beta cells
Insulin-producing beta cell

The nuts and bolts of immunotherapy 

Our immune system is normally made up of a balance of different types of immune cells, all working together to protect us against infections. But in Type 1 diabetes the immune system thinks insulin-producing beta cells are the enemy, and sets out to destroy them. 

In Type 1 diabetes there are three types of immune cells at work:

Killer T cells

 

‘Killer’ T cells: the assassins of the immune system.

They recognise and destroy harmful bacteria and viruses. But in Type 1, they mistakenly attack our beta cells.

 

Regulatory T cells

Regulatory T cells, or Tregs: the police of the immune system.

They call law and order by keeping killer T cells incheck. In Type 1, Tregs become outnumbered and can no longer turn off the killer T cells when they’re not needed. This means killer T cells are free to invade the pancreas and destroy beta cells.

B cells

B cells: the fire-starters.

B cells make proteins called antibodies. Antibodies stick to the surface of harmful germs to alert killer T cells to the presence of intruders. But in Type 1, B cells produce a type of antibody which recognises parts of our own body instead of germs, called autoantibodies.

Autoantibodies bind to beta cells, signalling that this cell needs to be destroyed. They can appear years – sometimes decades – before you’re diagnosed with Type 1 and they’re a sign that the immune attack is in motion. Because of this, we can test for autoantibodies to predict if someone will develop Type 1. 

Different immunotherapies work in different ways, but they all aim to stop the immune system from attacking the pancreas. Some try to teach the B cells to no longer see beta cells as their enemy. Others try to dampen down the activity of B cells or killer T cells, so they can’t play their role. And some treatments help the Treg police to protect the pancreas against an attack.

Who could immunotherapies help?

Scientists believe immunotherapies could help people with Type 1 diabetes at three stages.

Prevent

We can find people who have a high risk of Type 1 diabetes by looking at their genes or testing to see if they have autoantibodies in their blood. Immunotherapies could be given to those at risk before any of their beta cells have been destroyed, to try and stop Type 1 diabetes from developing, or at least delay it. 

Stop

When people have just been diagnosed with Type 1 diabetes the immune system hasn’t quite finished its attack, meaning that up to 20% of your beta cells are still alive. Immunotherapies could be used when someone is first diagnosed to preserve these beta cells. And the more beta cells we can protect, the more insulin you can produce on your own. This could make blood sugar control easier and protect you against serious complications down the line.

Cure

Immunotherapies could potentially help people already living with Type 1 diabetes. Scientists are looking for ways to replace or regenerate the beta cells that have been destroyed. Once we can do this, immunotherapies could be used alongside the beta cell therapy to protect these new cells from another immune system attack.

What stage is the research at?

Before any new treatments can be given outside of a research setting they have to be rigorously tested in clinical trials. Scientists are doing this with different immunotherapies right now. The majority of trials are involving people who are within 100 days of their diagnosis. But trials are also happening in people who don’t yet have Type 1 diabetes, but are at a high risk.

As a next step, we need further, larger clinical trials. The results then need to be put to regulatory bodies – who decide whether a new treatment is safe and effective – and grant it a licence. Only once an immunotherapy has been licensed can doctors can prescribe it.

What we're doing to get us there sooner 

We set up the Type 1 diabetes Immunotherapy Consortium in 2015, with an investment of £2.8 million and co-funding from JDRF. Its goal is to bring scientists together to speed up the clinical trial process and make the first immunotherapy available to people with Type 1 diabetes as soon as possible. 

We’re also funding research to further unravel what happens to the immune system in people with Type 1 diabetes, so scientists can find new and better therapies. 

 

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Professor Marelli-Berg is 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. 

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