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Splicing genes to treat kidney disease

Project summary

Modulation of VEGF-A splicing as a novel therapeutic strategy in diabetic nephropathy

Many people with diabetes develop kidney damage. We know that a protein called VEGF plays an important role in causing this damage. But another form of VEGF protects against kidney damage. Dr Sebastian Oltean wants to find new treatments that help people with diabetes to make more protective VEGF, to slow or prevent kidney damage. 

Background to research

Kidney disease, known as nephropathy, is a common complication of diabetes. When your kidneys are healthy, they keep important things that your body needs inside your blood, like protein. But in people with diabetes, blood vessels in kidneys can become damaged, and protein can leak out into the urine.

At the moment there aren’t any treatments for kidney damage and tightly controlling blood glucose levels doesn’t always stop this complication from developing. 

We know that a protein, called VEGF, plays a key role in making the kidneys ‘leaky’. But there are two versions of VEGF: one brings on this leaking and makes kidney damage worse, while the other has the opposite effect and helps to slow kidney damage.

The two versions of VEGF are produced by a process called alternative splicing. Alternative splicing is when sections of our DNA are turned into different versions of the same protein. But in people with diabetes, this process can go wrong.

Dr Oltean has already found that manipulating the levels of the two forms of VEGF affects kidney damage in mice. He’s also identified certain compounds which can affect VEGF splicing.

Research aims

Dr Oltean wants to find new treatments that can manipulate alternative splicing in people with diabetes, so that levels of the protective version of VEGF can be increased, to slow down kidney damage. 

Dr Oltean and his team will use pioneering techniques that identify the different forms of proteins made during alternative splicing. They’ll then study the impact of different compounds on alternative splicing, and test if they’re helpful in treating kidney disease in mice. 

Potential benefit to people with diabetes

At the moment, there aren’t any treatments that slow or stop kidney disease. Finding compounds that help to protect against kidney damage could lead to new kidney disease treatments.

In the future, this could improve health and quality of life for people with kidney disease, and help to prevent the complication.
 

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