Targeting autophagy in nephropathic cystinosis

Cystinosis is a genetic disorder due to a gene defect called cystinosin, where a toxic metabolite called cysteine collects in the cells due to a defect in lysosomes. This results in the kidneys become leaky to protein, water and salts, which results in growth failure, severe dehydration and developmental delay in children. A subtype of this disease (called nephropathic) results in kidney failure in children and young adults. The gene defect does not correlate with the kidney injury in patients. We and others have shown that targeted death (autophagy) of kidney cells causes the kidney injury and blocking this process can rescue the cells from this fate. In this grant we propose to understand the interplay of this specific injury in the human kidney, and to evaluate if gene defects in one of the key molecules in this cascade, called Clusterin (CLU), could be the confounder gene for the kidney injury in this disease. In addition, we propose to reposition a drug that blocks CLU as a possible new treatment to prevent and treat kidney damage in this condition.


Award Date
09 December 2016
Award Value
Principal Investigator
Dr Minnie Sarwal
Host Institution
University of California San Francisco
MRCG-HRB Joint Funding Scheme