Evaluation of a novel drug combination treatment for nephropathic cystinosis in a new cystinotic rat model.

Cystinosis is a rare disease that results in the build-up of cystine in all cells of the body. Cystine is a protein building block and normally the excess is moved out of cells. In cystinosis the transporter for cystine does not work and cystine builds up inside the cells and forms crystals which cause damage to all organs and muscles. 

The only treatment available is cysteamine, which removes excess cystine from the cells. However, even if taken regularly and from birth, the kidneys will stop working eventually. Other organs will also eventually fail. This drug needs to be taken regularly and in large doses. It tastes bad and causes bad breath and body odour, as well as damage to the stomach. It is common for small children to vomit daily and for young people to try to stop their treatment to avoid having continuous bad breath which negatively affects their health. To improve the lives of cystinosis patients there needs to be: 1) better versions of cysteamine that have fewer side effects and 2) new therapies to reduce damage to the kidneys (as cysteamine does not stop this). Addressing 1) a new version of cysteamine, CF10, has been developed that reduces cystine build-up in cells but lacks the side effects and can be taken in lower and less frequent doses. Tackling 2) we have shown in cells in the lab that using a drug called everolimus, the damage to the kidneys can be addressed. Using cysteamine and everolimus together all of the problems associated with cystinosis are corrected in these cell models.

In this proposal we will test, in a rat model, if the new drug combination of CF10/everolimus can provide a better treatment. This is a critical step towards enabling a clinical trial of these drugs and potential new treatment for cystinosis.

Award Date
01 July 2022
Award Value
Principal Investigator
Dr Jennifer Hollywood
Host Institution
University of Auckland
HRCI-HRB Joint Funding Scheme