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A potential treatment for extreme insulin resistance

Project summary

Investigation of anti-insulin receptor antibodies as a potential therapy for extreme insulin resistance due to insulin receptor mutations

Dr Robert Semple and his team will develop and evaluate the potential of proteins called antibodies for treating people with a type of extreme insulin resistance caused by rare genetic changes. They will also develop a diagnostic screening test that will identify people that are likely to respond to the therapeutic antibody treatment.

Background to research

Some people have rare genetic changes in a molecule called the insulin receptor. This receptor is the target of insulin in cells; if it is damaged and can't recognise insulin, a form of diabetes with extreme resistance to insulin develops. Having changes in both copies of the gene that codes the insulin receptor can lead to death in infancy or childhood. 

A great deal is known about the structure of the insulin receptor, and the consequences of these genetic changes. However, there is currently no really effective treatment for people that have the condition, and existing treatments have side effects. As an alternative strategy, research suggests that specially designed proteins called antibodies can bind to and activate the damaged insulin receptors in the lab. 

Research aims

Dr Robert Semple and his team will use the power of these specially created antibodies that are able to bind to and activate damaged insulin receptors. They will investigate how these antibodies are able to activate the receptors, and test whether the antibodies can lower blood glucose levels in mice that have the same genetic changes as people with this rare condition.

The team aim to take a major step towards developing these antibodies as a potential life-saving treatment for this rare type of diabetes, and the findings could also pave the way for the development of similar antibodies as potential treatments for more common forms of diabetes. The team plan to develop a diagnostic test that will identify people most likely to respond to this antibody treatment.

Potential benefit to people with diabetes

This research aims to test a new treatment for severe, life-threatening forms of diabetes caused by genetic changes that damage the insulin receptor. If successful, this new treatment could lead to potentially transformational improvements in the health and wellbeing of people with this rare condition. This research could also accelerate the development of antibodies as a potential treatment for more common forms of diabetes.

Adopted by Diabetes UK Groups Huntingdonshire Group In Memory of Joan Margaret Davies
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