Professor John Sayer and his team have recently completed a Rosetrees Trust-funded project which aimed to further develop their nephronophthisis (NPHP) mouse model, and subsequent treatment opportunities, at Newcastle University. NPHP is an early onset cystic kidney disease, and it is the lethal component of an incurable, inherited disorder known as Joubert syndrome. Currently, treatment options for NPHP are limited to symptomatic therapy. Therefore, Professor Sayer’s research will help bring treatments for NPHP to the clinic.
In their latest paper, published in the Proceedings of the National Academy of Sciences (PNAS), Rosetrees Trust funding has helped support their research on the identification of a “modifier gene” involved in cystic kidney disease. Using their mouse model, they showed for the first time that the single locus, Barttin, is a modifier. Then, in a cohort of patients, they also showed that the human homolog plays a similar role in disease. These findings provide researchers with a novel potential target to exploit in their model systems, which could have future use in patients. Through altering levels of modifier genes, this may alleviate the effects of Joubert syndrome.
Professor Sayer said: “We have elegantly shown using mouse and human DNA samples that Barttin modifies the severity of kidney disease in Joubert syndrome. This is the first time that a modifier gene for cystic kidney disease has been identified. This information will improve diagnoses and will be used to develop therapies to reduce the severity of kidney disease in affected patients.”
“Our research is a major step forwards proving the power of using mouse models to study rare human inherited disease and in the future we may be able to offer a therapy that switches on the protective modifier gene and reduces the development of genetic kidney disease.
“This work paves the way towards personalised therapies in patients with the inherited kidney disease.”
Overall, this research offers new hope to understanding the genetic, and mechanistic, basis of rare diseases to ultimately improve diagnoses and treatment options.
Written by: Dr. Rebecca Downing and Professor John Sayer