Repurposing Drugs May Help Fast-track Clinical Trials Aimed at Slowing Alport Syndrome Progression

The Alport Syndrome Foundation awarded Dr. Benjamin Humphreys, Joseph Friedman Professor of Renal Diseases in Medicine and Chief, Division of Nephrology, a two-year, $125,000 grant for his proposal “Tubulointerstitial Profiling for Alport Syndrome Target Identification.”

Alport Syndrome results from damage caused to podocytes, cells that help form the filtration barrier within the glomerulus.  Damage to podocytes causes them to behave like a “leaky filter,” allowing proteins to pass into the urine.  This leaked protein is toxic to downstream proximal tubule cells and leads to scar formation from myofibroblasts (cells that secrete scar proteins), ultimately causing kidney failure.

Humphreys’ group has previously performed comprehensive genetic profiling of all the genes expressed in both proximal tubule cells and myofibroblasts in a mouse model of Alport Syndrome.  The Alport grant will enable them to analyze this enormous dataset to identify critical pathways upregulated between these cell types during Alport Syndrome progression.

Jeffrey Miner, PhD, will collaborate on Alport Study

In collaboration with Jeffrey Miner, PhD, Professor of Medicine in the Division of Nephrology and an expert in Alport Syndrome research, the study will identify candidate drugs that could interrupt the pathways and slow Alport Syndrome progression.

Importantly, Humphrey’s group will select pathways for which drugs already exist for other indications, and then test the ability of such drugs to slow progression in a mouse model of Alport Syndrome.

These studies are important for two reasons.  “First, there has been no comprehensive, cell-specific analysis of all of the gene expression changes that occur in proximal tubule and myofibroblasts in Alport Syndrome,” Humphreys points out.  “The genetic profiling atlas that we generate will serve as a highly useful resource for the Alport Syndrome research community.

“Second, we will be testing drugs that are already entered into clinical trials to treat other diseases – such as cancer – and testing them in a mouse model of Alport Syndrome.  If any of these drugs do slow progression, translation to an Alport Syndrome clinical trial will be much faster since the drugs have been in human trials for other indications.”

Follow Dr. Humphreys and Miner on Twitter @HumphreysLab and @JeffMinerPhD.