Autosomal dominant polycystic kidney disease (ADPKD) affects about 12 million people worldwide, with half developing end-stage kidney disease by age 60, according to the study. "Once the kidneys have failed, the only options for survival are dialysis or a kidney transplant," Dr. Patel said. "A large percentage of ADPKD patients on dialysis die each year while waiting for a donated kidney."
The only drug currently approved to treat ADPKD, called Jynarque (generic name tolvaptan), carries the FDA's highest warning in its prescribing information, a box notifying prescribers and users of the possibility of "serious and potentially fatal liver injury."
The new treatment cooperatively developed at UT Southwestern and Regulus Therapeutics Inc., a biopharmaceutical company based in California, showed no evidence of toxicity in animals or in human cell tests, according to the study. It is preferentially delivered to kidneys rather than the liver after being administered, according to the Nature Communications study.
"We earlier showed that levels of a tiny RNA fragment called microRNA-17 are increased in models of ADPKD," Dr. Patel said. "MicroRNA-17 interferes with the normal function of other, beneficial RNAs, causing kidney cysts to grow. RGLS4326, as the new drug is called in development, works by blocking the harmful microRNA-17."
Early phase one clinical trials began last year, conducted by Regulus Therapeutics. The FDA has asked for additional toxicity information from animal testing before human trials can move to the next step, Dr. Patel said.
Edmund C Lee, Tania Valencia, Charles Allerson, Annelie Schairer, Andrea Flaten, Matanel Yheskel, Kara Kersjes, Jian Li, Sole Gatto, Mandeep Takhar, Steven Lockton, Adam Pavlicek, Michael Kim, Tiffany Chu, Randy Soriano, Scott Davis, John R Androsavich, Salma Sarwary, Tate Owen, Julia Kaplan, Kai Liu, Graham Jang, Steven Neben, Philip Bentley, Timothy Wright, Vishal Patel.
Discovery and preclinical evaluation of anti-miR-17 oligonucleotide RGLS4326 for the treatment of polycystic kidney disease.
Nature Communicationsvolume 10, Article number: 4148 (2019). doi: 10.1038/s41467-019-11918-y