Could new treatments protect the kidneys and bladder in boys with posterior urethral valves?
Posterior urethral valves (PUVs) can develop in boys before they are born. PUVs are rare and affect bladder, with a proportion of boys having kidney damage, and some developing kidney failure. There is currently no cure for PUVs. With our support, generously co-funded by The Cook Fund, of £245,000, Dr Carolina Bebi and her team will test whether new treatments that target the lymphatic system of the bladder could protect the kidneys and bladder in boys with PUVs.
We need new treatments for posterior urethral valves
Posterior urethral valves are flaps of tissue which cause a blockage in the urethra. The urethra is a tube which carries urine when from where it is stored in the bladder out of the body, so we can wee. When there is a PUV, the flap of tissue blocks the flow of urine causing it to build up in the bladder. This creates pressure inside the bladder, stretching and damaging it.
The blockage in the urethra can be removed by surgery after birth in boys with PUVs. However permanent damage to the bladder has already happened which makes it stiffer and less able to hold urine. This can cause difficulties weeing and lead to infections. These infections can spread to the kidneys. Depending on the amount of damage to the bladder, boys may need surgery to increase how much urine the bladder can hold.
Research is difficult for a rare condition, partly because of the limited data available. However small studies have shown over a third of patients with PUVs go on to develop kidney problems, and some of these patients will reach kidney failure.
New targets for treatments
There is currently no cure for PUVs, and we don’t know what causes PUVs to develop.
Lymphatic vessels could be a new target to protect the bladder in PUVs. The lymphatic vessels are tiny tubes which remove fluid and waste from our organs. In other organs, such as in the heart, brain and kidney, the lymphatics also help with repair of tissue. However, little is known about the lymphatics of the bladder, including whether they can also help with repair.
Meet Dr Carolina Bebi
Dr Carolina Bebi is a urologist and works at Great Ormond Street Hospital (GOSH) Institute of Child Health (ICH) researching the lymphatics of the bladder and whether they can be targeted with treatments in childhood diseases that affect bladder health.
The LifeArc–Kidney Research UK Centre for Rare Kidney Disease training fellowship of £245,000 will mean Carolina and her team can look at the lymphatics of the bladder in PUVs and test whether new treatments can be delivered using gene therapy to improve the lymphatics and health of the bladder.
“Research has shown many roles of the lymphatic system that go beyond draining the tissues of fluid. In organs such as the heart, improving the lymphatics has helped slow the stiffening and build-up of scar tissue seen with tissue damage in certain conditions affecting the heart.
"This process of tissue damage, called fibrosis, also damages the bladder in PUVs. By targeting the bladder lymphatics this type of treatment could help protect the bladder in PUVs.” Dr Carolina Bebi
Could gene therapy protect the bladder?
Carolina and her team will look at the lymphatic system of the bladder in models of PUVs, and in bladder samples removed during surgery to treat children with PUVs. Using special 3D imaging, they will look at whether the lymphatics of the bladder change with PUVs, and whether this is linked to kidney damage.
Using their laboratory model of PUVs, Carolina and her team will use gene therapy to deliver a substance to the bladder that helps lymphatic vessels grow. This PUV model will be studied to see whether the gene therapy treatment improves bladder and kidney health.
Looking for future treatments
By understanding the lymphatics of the bladder this could identify new treatment targets to help protect bladder and kidney health in conditions such as PUVs. Finding ways to deliver substances to the bladder lymphatics using gene therapy could help inform how future treatments can be successfully delivered.
“As a urologist I have met many boys with PUVs and their families. These boys can have many urinary tract infections, bladder problems and may need multiple surgeries. Some will need dialysis. This condition can have a huge impact on many aspects of their lives…for example some will miss many hours of school.
We urgently need better treatments for this condition. Current approaches are after the damage has already been done to the bladder and kidneys. The aim of my research is to protect the bladder and kidneys before they become damaged. I hope this improves the lives of boys with PUVs and their families in the future.” Dr Carolina Bebi
The Cook Fund
Nick and Helen Cook are parents to three sons, all of whom have kidney disease. In collaboration with Kidney Research UK, they have developed The Cook Fund programme which is funding new research into kidney disease.
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