Skip to main content
Research

Genetically unique siblings reveal new treatment target for type 1 diabetes

Two siblings who have unique changes in a key gene have given researchers new insights that could help lead to innovative new treatments in type 1 diabetes.
JDRF logo placeholder for author profile picture
Josie Clarkson 18 April 2024
Content last reviewed and updated: 18.04.2024

Two young children sat on the floor hugging each other.

There are lots of genes that are associated with an increased risk of developing type 1 diabetes. Studying these genes can provide researchers with new ideas for treatments for type 1, so the University of Exeter offers free worldwide screening for babies diagnosed with type 1 before they are 9 months old.

A unique genetic difference

New research from University of Exeter, co-funded by JDRF and published in the Journal of Experimental Medicine, studies two siblings who were diagnosed with a rare genetic form of autoimmune diabetes in the first weeks of life. Autoimmunity is where the immune system attacks our body’s own cells – in this case, the insulin-making beta cells.

The changes in their genes (known as a genetic mutation) have not been found in anyone else. The siblings’ mutation is in the gene for a protein called programmed death-ligand 1 (PD-L1) and the researchers think it could be responsible for their very-early-onset autoimmune diabetes.

Insights from cancer therapy

Some cancer patients are treated with a type of immunotherapy that stops PD-L1 from working. These people can develop autoimmune diabetes because of the treatment. We don’t know why only this cancer immunotherapy triggers autoimmune diabetes. The siblings’ genetic mutation results in the same effect as the cancer treatment, shedding new light on the involvement of PD-L1 in type 1 diabetes.

A new research avenue

Study co-author Professor Timothy Tree, from King’s College London, said: “This finding increases our knowledge of how autoimmune forms of diabetes such as type 1 diabetes develop. It opens up a new potential target for treatments that could prevent diabetes in the future. Simultaneously, it gives new knowledge to the cancer immunotherapy field by uniquely providing the results of completely disabling PD-L1 in a person, something you could never manipulate in studies. Reducing PD-L1 is already effective for cancer treatment, and boosting it is now being investigated as a type 1 diabetes treatment – our findings will help accelerate the search for new and better drugs.”

Next steps for the research

“Through studying this one set of siblings – unique in the world to our knowledge – we have found that the PD-L1 gene is essential for avoiding autoimmune diabetes but is not essential for ‘everyday’ immune function. This leads us to the grand question; ‘what is the role of PD-L1 in our pancreas making it critical for preventing our immune cells destroying our beta cells?’ We know that under certain conditions beta cells express PD-L1. However, certain types of immune cells in the pancreas also express PD-L1. We now need to work out the communication between different cell types that is critical for preventing autoimmune diabetes.”

Learn about another of Professor Tim Tree’s JDRF-funded research projects.

More research news

Read more
A row of vials of clear liquid with black lids. A blue gloved hand is pinching the top of the closest vial as if to pick it up.
13 May 2024

Novel insulin being developed to enable implantable insulin pumps

Medtronic Diabetes have announced they are funding the biopharmaceutical company Arecor Therapeutics to develop a novel, highly concentrated, thermostable insulin, which will be specialised for use in implantable insulin pumps.

Read more
Professor Colin Dayan at Cardiff University, working on immunotherapy for type 1 diabetes cure research
Research
18 April 2024

Professor Colin Dayan presented with the 2023 JDRF Rumbough Award 

The award recognises Professor Dayan’s remarkable accomplishments in type 1 diabetes research.

Read more
A female doctor works at a laptop on a table. She is wearing a shirt and glasses with a stethoscope around her neck.
17 April 2024

New international medical code launches for presymptomatic type 1 diabetes

JDRF-funded researchers from the University of Birmingham have joined forces with NHS England to develop a diagnostic code for use on electronic medical records of people in the earliest stages of type 1 diabetes, allowing them to receive better, more timely healthcare and access to emerging treatments.

Read more
Professor Richard Oram in the Research, Innovation, Learning and Development (RILD) building at the University of Exeter.
7 March 2024

New biochip launches that detects genetic risk of type 1 diabetes

A new test by Randox, developed with JDRF-funded researchers at the University of Exeter, is the first in the world to use genetics to quickly identify who is at high risk of developing type 1 diabetes.