Unmet Need: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive enlargement of multiple renal cysts, leading to chronic pain, hypertension, and decline in renal function and renal failure in a substantial subset of patients. Fluid enters the cysts via a cAMP-dependent process involving the cystic fibrosis transmembrane conductance regulator (CFTR) in the luminal membrane of cysts in ADPKD patients. Disclosed herein is the use of CFTR-modulators for the treatment of ADPKD.
Technical Details: Johns Hopkins researchers have discovered a new use for CFTR modulators for the treatment of ADPKD. Inventors observed a significant inhibition of growth in cysts grown in cell culture, both in the presence or absence of the cAMP-activator Forskolin. Importantly, a CFTR modulator already approved for use in CF patients, reduced cyst growth and improved renal function in several mouse models of ADPKD. Interestingly, the CFTR modulator increases the expression of CFTR in the basolateral cell membrane of the cysts and restores a network of proteostatic proteins that when misregulated contribute to cyst growth. Together, this invention uncovered a promising new strategy for the use of CFTR correctors either alone, or possibly in combination for the treatment of ADPKD.
Value Proposition:
· Reduction of cyst growth and prevention and treatment of ADPKD through a novel mechanism involving the induction of cyst fluid reduction by CFTR modulators
· Monotherapy or together with a combination of modulators.
Looking for Partners to: Develop & commercialize the technology as a novel therapeutic strategy for ADPKD.
Stage of Development: Pre-Clinical
Data Availability: In vitro
Inventors: Liudmila Cebotaru
Patent Status: Pending US20200289482 JP2020525446 EP3641763 W0/2018/237174
Publications: Yanda MK, Cha B, Cebotaru C, Cebotaru L. Pharmacological reversal of renal cysts from secretion to absorption suggests a potential therapeutic strategy for managing polycystic kidney disease. J Biol Chem. 2019 Nov. PMID: 31570523. Yanda M, Liu Q, Cebotaru L., A potential strategy for reducing cysts in autosomal dominant polycystic kidney disease with a CFTR corrector. J Biol Chem. 2018 Jun 6. pii: jbc. RA118.001846. PMID: 29875161
