The research project has shown that just one dose of gene therapy targeting cells in the kidney has the potential to cure a condition known as steroid-resistant nephrotic syndrome.
The research project received early funding from charity Kidney Research UK and the Wellcome Trust and has gone on to gain further support from Purespring Therapeutics.
The findings by the team in Bristol led by Professor Moin Saleem from the Bristol Medical School, suggested that replacing one faulty gene that codes for a protein known as podocin could cure the condition. Podocin is a protein essential for the functioning of cells called podocytes which have a critical role within the kidney’s filtration system.
Nephrotic syndrome is a condition where the kidney's filtering units are damaged, allowing large amounts of protein that should be kept in the bloodstream to leak into the urine. This can lead to swelling, particularly in the eyes and legs, and an increased risk of infections and blood clots, and the risk of kidney damage. It can occur at any age but is most commonly diagnosed in children under five years old.
Often the symptoms can be managed with steroids, however, around 10% of children with nephrotic syndrome do not respond to steroids and many will go on to develop kidney failure and will need dialysis or transplant within two to five years. This is the group where a faulty gene is frequently the cause of the disease. Using adeno-associated virus (AAV) they delivered the podocin gene to the correct cell type and were able to replace the original faulty gene in the podocytes, successfully treating several different laboratory-based models of nephrotic syndrome.
‘Adeno-associated virus gene therapy prevents progression of kidney disease in genetic models of nephrotic syndrome’ by W. Ding, V. Kuzmuk, S. Hunter, A. Lay, B. Hayes, M. Beesley, R. Rollason, J. Hurcombe, F. Barrington, M. Saleem et al. in Science Translational Medicine