Renal Cysts and Diabetes (RCAD) syndrome, or HNF1B-associated nephropathy which is also known as MODY5, is one of the rare genetic diseases that is defined by a combination of cystic developmental anomalies of the kidneys and diabetes mellitus type 2. Protheragen caters to the very specific pathophysiology underlying RCAD syndrome by providing comprehensive preclinical drug and therapy development services.
Introduction to Renal Cysts and Diabetes Syndrome
RCAD syndrome is an autosomal dominant genetic disorder due to mutation or deletion of the HNF1B gene. MODY 5 is one of the recognized subtypes of Maturity Onset Diabetes of the Young (MODY), and is also one of the major monogenic etiological factors of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT). Its incidence is said to be around 1-10 in 100,000, although it has likely been underdiagnosed due to phenotypic variability and de novo mutations.
Pathogenesis of Renal Cysts and Diabetes Syndrome
The RCAD syndrome can be traced to heterozygous pathogenic mutations within the HNF1B gene which leads to haploinsufficient expression of the HNF1B transcription factor. HNF1B functions as a master switch in the processes of gene expression in multi-organ systems like the kidneys, pancreas, liver and urinary system and the fundamental unit of excretion, the nephron. During the progression of the kidney, HNF1B is important for the branching of ureteric bud, nephron development and the functioning of its most proximal tubule. Its absence causes renal hypoplasia and cystic kidneys with obsolescence of significant structures, leading to disruption of renal function.
Fig.1 Distribution of mutations within the gene that encodes hepatocyte nuclear factor 1β. (Clissold, 2015)
Therapeutics Development for Renal Cysts and Diabetes Syndrome
| Drug Name |
Therapeutic Target |
Key Mechanisms/Advances |
Development Stage |
| Metformin |
AMPK activator, mTORC1 inhibition |
Reduces cyst volume in PKD models |
Preclinical research (PKD) |
| Salsalate |
cAMP-PKA signaling inhibition |
Delays cyst growth in adult-onset PKD models |
Phase II trial preparation |
| Canagliflozin |
SGLT2 inhibitor, reduces hyperfiltration |
Lowers ESRD risk in diabetic nephropathy |
Approved |
| Losartan |
AT1 receptor antagonist |
Reduces ESRD risk in diabetic nephropathy |
Approved |
| Pirfenidone |
Multi-target antifibrotic (TNF-α, IL-6) |
Reduces renal fibrosis in preclinical models |
Preclinical |
| Bardoxolone Methyl |
Nrf2 activator, NF-κB/TGF-β inhibition |
Improves eGFR with potential safety concerns |
Phase III trial paused |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen is a comprehensive preclinical service provider dedicated to the discovery and development of novel therapeutics for RCAD syndrome. Our extensive therapeutic development services incorporate the use of sophisticated disease models that effectively capture important features of this inherited disorder, with particular emphasis on the renal and pancreatic manifestations.
Therapeutic Development Platforms for Renal Cysts and Diabetes Syndrome
Disease Models Development for Renal Cysts and Diabetes Syndrome
Protheragen offers innovative and comprehensive disease models to advance preclinical research into RCAD syndrome. Our platform integrates cell-based models, kidney organoids, and animal models to effectively capture the genetic and developmental signatures of RCAD syndrome.
- HNF1B-KO HK-2 Cells
- Patient-Derived iPSCs
- SGLT2-Overexpressing HEK293 Cells
- HNF1B-Mutant Kidney Organoids
- Cystic ECM Hydrogel Model
- Hnf1bflox/flox; Pax8-Cre Mice
- HNF1BE354K Knock-in Rats
- Patient-Derived Organoid Xenografts
- HNF1B Rescue Model
- Cytochrome P450-Humanized RCAD Mice
Protheragen's integrated preclinical development solutions are specifically designed for research in rare genetic disorders affecting renal and metabolic systems, such as RCAD syndrome. We specialize in disease model development, pharmacokinetics, and drug safety evaluation, enabling us to support your investigation.
Contact us today to accelerate your renal cysts and diabetes syndrome research with end-to-end solutions.
References
- Clissold, R. L., et al. "Hnf1b-Associated Renal and Extra-Renal Disease-an Expanding Clinical Spectrum." Nat Rev Nephrol 11.2 (2015): 102-12.
- Cui, S., et al. "Establishment of Plafmci005-a Induced Pluripotent Stem Cells Derived from Pbmc from a Patient with Renal Cysts and Diabetes Syndrome." Stem Cell Res 55 (2021): 102485.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
