ARPKD PhD 3-year research grant award
The PKD Charity, Arran Brown Rainbow Foundation and University of Wolverhampton are jointly funding a pioneering 3-year ARPKD research project at Wolverhampton and UCL London.
What is ARPKD?
ARPKD (autosomal recessive polycystic kidney disease) is a rare disease that affects the kidneys and liver. It is usually diagnosed in babies and young children and occurs in roughly one in every 20,000 live births. ARPKD causes cysts to develop in the small tubes of the kidneys. ARPKD also causes problems with the liver, including the formation of scar tissue (called fibrosis), and a swollen bile duct.
Although ARPKD affects the kidneys and liver, the immediate risk to about a third of babies born with the disease is lung underdevelopment. This can make it difficult for the baby to breathe and they may need emergency breathing support from a machine (ventilation). Sadly, some babies don’t survive pregnancy or birth.
Over time, ARPKD causes damage to the kidneys, stopping them working properly, and eventually leading to kidney failure, often during childhood or young adulthood. It can also cause complications in the liver and bile duct, such as infections.
ARPKD symptoms, severity of disease and the age that problems occur vary between different people. For example, some babies have serious lung and kidney problems, but others do not; and some children and adults have mainly kidney symptoms, while others have mainly liver problems.
There are no drugs to treat or slow down ARPKD. Children with kidney failure will need either dialysis or a kidney transplant. Some children may also need a liver transplant.
Genetic influence on ARPKD progression
ARPKD is caused by a change in the DNA of one of the building blocks of the cell that controls how signals are communicated in the cell. This change in DNA and cell miscommunication causes cysts to form in the kidneys and expand in size and number with age.
The rate at which cysts form and expand might depend on the interactions of the various genes and building blocks of the cell with each other. One of these genes is called ATMIN. Previous research funded by the PKD Charity has shown that ATMIN modifies how signals are communicated in kidney cells, affecting kidney formation.
Novel research project
During this 3-year project, researchers will investigate ATMIN’s interactions with the main gene that causes ARPKD (called PKHD1), because they believe that ATMIN might be a useful target for novel therapies to treat ARPKD. Normal and diseased cells will be studied to see how defects in these genetic interactions relate to disease progression and severity. At the end, they will have greater understanding of the variation in disease severity and impact on diagnosis and prognosis.
The research will be undertaken at Wolverhampton University and UCL Centre for Nephrology London by Taylor Richards, a PhD student. He will be supervised by Dr Evi Goggolidou and Professor Pat Wilson.
About Arran Brown
Arran Brown was born with ARPKD and died just after his first birthday. He spent most of his life in hospital and although he returned often to his family home in Cumbernauld, his longest uninterrupted period at home was just six weeks. Any slight cold had a severe impact on him and he was ventilated on five occasions. He also suffered at least three cardiac arrests brought on by breathing issues.
Despite all the trials that Arran faced in his life, he remained a very happy child with an amazingly infectious smile. Whether laughing and waving, playing peek-a-boo, or constantly repeating the word ‘Hiya’ he would brighten up any room and the mood of those around him. He would wave out of the window from his hospital bed at all who passed. Even the most stubborn of doctors would check for his wave and smile broadly back.
Arran passed away on 20th May 2011, peacefully in the arms of his mother and holding his dad’s hand, surrounded by close family and friends. He remains an inspiration to so many.
The Arran Brown Rainbow Foundation is a registered Scottish Charity (SCO42510) set up in 2011 in memory of Arran Brown.
Alasdair Brown, Arran’s father, explains why the Arran Brown Rainbow Foundation is funding this research with the PKD Charity: “The rate of growth of the cysts within Arran’s kidneys applied a constant pressure and strain on his other organs preventing them from developing. Research that can help to progress the understanding of cyst formation and expansion is perfectly aligned with the aims of our charity, and it may ultimately lead to helping those impacted by the disease.”