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Home > About BTT1D & Our Impact > Our research > Research projects > Developing a drug to protect insulin-producing beta cells
Dr Gavin Bewick, a type 1 diabetes researcher working on developing a drug to protect beta cells, in his lab.
Beta cells are cells in the pancreas that produce and release insulin. In type 1 diabetes, the immune system mistakenly attacks and destroys beta cells. At diagnosis, a person with type 1 typically has just 10-20% of their beta cells left. At this point their body can no longer produce enough insulin to regulate the level of glucose in their blood.
Gavin and his team are trying to find a way to boost the health, function and amount of beta cells a person with type 1 has, so that they may no longer need to rely on insulin injections or insulin pumps. Ideally, this research could lead to a drug that could regenerate beta cells so that they are functional. This would mean they could help to control glucose in a person with type 1, lessening – or even eradicating – their reliance on external insulin.
Drugs work by binding to proteins on the surface of cells called receptors. This activates or inhibits the receptor causing an effect within the cell.
In his last Breakthrough T1D UK-supported project, Gavin showed that activation of a specific receptor – called the NPY receptor – protects human beta cells from damage. He found that it can do this without preventing insulin release. Gavin’s work highlighted the NPY receptor as a promising target for drugs which could bind to it and activate it.
Gavin’s previous research also identified a promising synthetic drug called K22, which can activate the NPY receptor. He and his team discovered that K22 protects the pancreatic islets (clusters of cells which contain beta cells) from invasion and attack by a type of immune cell called a macrophage. To understand K22’s true potential for treating type 1, Gavin aims to learn how it protects the insulin-producing beta cells from damage.
In this study, Gavin’s team will test whether the drug K22 can activate the NPY receptor to prevent beta cells dying and help them retain their function. NPY receptors are also found in organs throughout the body, including the brain. So the researchers aim to fine tune the drug so that it only activates the receptors in the pancreas. This will enhance the protective ability of K22 and reduce any potential side effects.
The team at King’s College London will begin by collaborating with a lab in the US to figure out which cells within the pancreas contain NPY receptors. Next, to reveal the underlying biology involved, Gavin will expose pancreas samples from donors to K22 before separating and examining the individual cells within them. His research team will also run several experiments with different immune cells to work out how K22 protects beta cells from the immune system.
Equipped with this vital knowledge, Gavin can begin developing a new version of the drug that specifically targets the pancreas cells. If this project is successful, his next step would be to design and carry out clinical trials to evaluate the drug’s safety and effectiveness in humans.
Gavin’s grant from Breakthrough T1D UK includes funding for a researcher called Dr Naila Haq. Naila takes on the bulk of the day-to-day lab work. She grows 3D clusters of beta cells and immune cells and studies them through powerful microscopes alongside donated pancreas samples.
Gavin and Naila hope their research will lead to a treatment which can restore a healthy population of beta cells in people who already have type 1. The drug would protect their beta cells from damage, make remaining beta cells function more efficiently, and increase their number. This would lower the amount of insulin people with type 1 would have to give themselves and likely reduce their hypos. This would ultimately make type 1 more manageable and less dangerous. It may also halt or delay progression of type 1 in people recently diagnosed with the condition.
Breakthrough T1D UK funded Gavin’s previous project to find out more about the NPY receptor and drug K22. We are also funding Dr Rocio Sancho’s project at Kings College London, where her team is growing new beta cells in their lab from stem cells (cells that can develop into many other types of cell).
This award will help to fund the next generation of immunotherapy research, enabling more efficient clinical trials, in more locations, so that promising treatments can reach people sooner.
This project aims to overcome two major roadblocks to developing and licensing immunotherapies for people newly diagnosed with type 1 diabetes.
Dr Bewick is exploring ways to improve the health, performance and number of beta cells in the body, so that people with type 1 can be less reliant on insulin pumps and injections – or even, one day, live without them completely.
This project is looking at a new way to turn stem cells into beta cells in the lab, to better understand what conditions make this process happen efficiently.
