Renal ciliopathies are genetic disorders impacting kidney function due to dysfunctions in cilia. These conditions, including Autosomal Dominant and Recessive Polycystic Kidney Diseases, present unique challenges in the medical field. Our company is dedicated to developing innovative therapies to address these challenges, enhancing the potential for breakthroughs in kidney disease therapeutics.
Introduction to Renal Ciliopathies
Renal ciliopathies are a group of inherited disorders characterized by defects in cilia function, with major implications for kidney health and function. Notable conditions include Autosomal Dominant Polycystic Kidney Disease (ADPKD), affecting approximately 1 in 400 to 1,000 individuals, and Autosomal Recessive Polycystic Kidney Disease (ARPKD), which is rarer, impacting about 1 in 20,000 individuals. These disorders result in significant renal complications, necessitating novel therapeutic approaches.
Fig.1 Clinical phenotypes and molecular genetics of renal ciliopathies. (Devlin, L., P. Dhondurao Sudhindar, and J. A. Sayer., 2023)
Promising Drug Targets for Renal Ciliopathies
Preclinical research in renal ciliopathies has identified several promising drug targets that focus on the intricate molecular pathways driving these disorders. These targets primarily aim to address the mechanisms of disease progression, such as abnormal cellular metabolism, signaling pathways, inflammation, and structural anomalies in kidney cells.
Targeting Transmembrane Channels:
ADPKD treatment includes Tolvaptan, which targets the arginine vasopressin receptor 2 (AV2R). This drug mitigates disease progression by influencing cAMP and PKA pathways, crucial in controlling fluid secretion and cyst formation in kidneys.
Targeting Cellular Metabolism:
The mTOR pathway is targeted due to its role in excessive cell growth and cyst formation. Rapamycin, an mTOR inhibitor, has shown effectiveness in reducing cystogenesis in animal models. Despite mixed results in human trials, it remains a significant focus for developing treatments that can regulate cellular metabolism and slow disease progress.
Fig.2 Renal ciliopathies and potential drug targets and prospects for clinical trials. (Devlin, L., P. Dhondurao Sudhindar, and J. A. Sayer., 2023)
Therapeutics Development for Renal Ciliopathies
Cell therapy and gene therapy represent a significant shift from traditional therapy paradigms, focusing on correcting underlying genetic causes or replacing damaged cellular components, and hold the promise of transforming the management of renal ciliopathies.
Table.1 Molecular targets, drug compounds, preclinical trials, and clinical trials for renal ciliopathies. (Devlin, L., P. Dhondurao Sudhindar, and J. A. Sayer., 2023)
| Molecular target |
Renal Ciliopathy Disease |
Drug Compound |
Preclinical Studies |
Clinical trials |
| Vasopressin receptor 2 (VR2) |
Upregulated in ADPKD, ARPKD and NPHP, increasing epithelial cell proliferation and fluid secretion promoting cystogenesis. |
Tolvaptan (AV2R inhibitor) |
PCK rat (ARPKD), pcy mouse (NPHP), Pkd1 mouse (ADPKD) |
ADPKD, ARPKD |
| Cystic fibrosis transmembrane conductance regulator (CFTR) |
Upregulated in ADPKD, contributing to increased chloride transport and fluid secretion, promoting cystogenesis. |
CFTR inhibitors (CFTR inhibitor) (Tetrazolo-CFTR-172, Ph-GlyH-101) |
Pkd1 mouse (ADPKD) |
N/A |
| Glycosphingolipids |
Glycosphingolipids accumulate in PKD models. |
Genz-123346 |
Pkd1 mice (ADPKD), jck mice, pcy mice (NPHP) |
N/A |
| Cyclooxygenase 2 (COX2) |
COX2 is upregulated in PKD and NPHP disease models. |
Celecoxib (COX2 inhibitors) |
Pkd2 mouse (ADPKD), Han: SPRD rat (NPHP) |
Preclinical |
| c-Src |
EGF is upregulated in PKD/ |
Bosutinib (multikinease inhibitor of c-Src) |
Bpk mice (ARPKD), PCK rat (ARPKD), Pkd1 mouse (ADPKD) |
ADPKD |
| Hedgehog (Hh) |
Hh signaling is dysregulated in renal ciliopathies. |
Purmorphamine (Hh agonist) |
Cep290 mouse model and human cells (NPHP) |
N/A |
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
At our company, we take pride in offering a comprehensive suite of services designed to support our clients in developing groundbreaking therapies for renal ciliopathies. Our dedicated team of expert scientists, nephrologists, and geneticists leverages cutting-edge technologies and extensive expertise in the field to expedite the progress of your therapeutic initiatives.
Therapeutic Development Services
Disease Model Development Services
- Cell-based Models Development Service
- Organoid Models Development Service
- Genetically Engineering Model Development
- Induced Disease Model Development
- Humanized Animal Model Development
- Syngeneic Model Development
- Xenograft Model Development
Types of Renal Ciliopathies
Leveraging our extensive expertise, we are dedicated to supporting the research and development of therapies for a wide array of renal ciliopathies. Each disorder exhibits unique genetic traits and pathological mechanisms, and our team possesses a deep understanding of these complexities. We offer customized solutions for each type of renal ciliopathy, accelerating the discovery and implementation of effective therapies to meet the specific needs of this challenging field.
| A-C |
C-M |
M-S |
- Alström's Syndrome
- APOL1 Related Nephropathy
- Atypical Hemolytic Uremic Syndrome (aHUS)
- Autosomal Dominant Polycystic Kidney Disease
- Autosomal Recessive Polycystic Kidney Disease
- Bardet-Biedl Syndrome
|
- C3 Glomerulonephritis (C3GN)
- C3 Glomerulopathy (C3G)
- Cranioectodermal Dysplasia
- Jeune's Dyndrome
- Joubert's Syndrome
- Meckel-Gruber Syndrome
- Medullary Cystic Kidney Disease
|
- Membranoproliferative Glomerulonephritis
- Nephronophthisis
- Oral-Facial-Digital Syndrome Type 1
- Renal-Hepatic-Pancreatic Dysplasia
- Sensenbrenner Syndrome
|
Our company is dedicated to delivering comprehensive, one-stop preclinical development services that address every facet of the process. Additionally, we provide
pharmacokinetics and
drug safety evaluation services, ensuring a seamless and fully integrated experience for our clients. If you are interested in our services, please don't hesitate to
contact us.
References
- Devlin, L., P. Dhondurao Sudhindar, and J. A. Sayer. "Renal Ciliopathies: Promising Drug Targets and Prospects for Clinical Trials." Expert Opin Ther Targets 27.4-5 (2023): 325-46.
- McConnachie, D. J., J. L. Stow, and A. J. Mallett. "Ciliopathies and the Kidney: A Review." Am J Kidney Dis 77.3 (2021): 410-19.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
