Renal coloboma syndrome (RCS), a rare genetic disorder, is most often associated with severe renal anomalies and optic disc coloboma and is usually due to mutations in the PAX2 gene. Protheragen provides comprehensive preclinical drug and therapy development services specifically tailored to address the unique mechanisms of RCS, with a focused expertise on renal-related therapeutic strategies.
Overview of Renal Coloboma Syndrome
Renal coloboma syndrome (RCS), often referred to as Papillorenal syndrome, is a rare genetic disorder with dominant inheritance pattern and heterogeneous expression. RCS occurs due to a combination of renal abnormalities and optic nerve dysgenesis. As with many congenital disorders, estimating the prevalence is challenging due to overlapping features with other CAKUT (Congenital Anomalies of the Kidney and Urinary Tract) types as well as variability in presentation. However, it is well known that PAX2 mutations are responsible for a large proportion of hereditary renal hypodysplasia cases.
Pathogenesis of Renal Coloboma Syndrome
The primary pathophysiology of RCS is attributed to loss-of-function mutations or deletions within the PAX2 gene that result in heterozygous PAX2 gene alterations. Talking specifically about PAX2, its role is crucial on the basis that it codes for an essential transcription factor which is fundamental in the process of NH embryonic development. Developmental malfunctions of the kidney owing to too little functional PAX2 protein which is known to disrupt reciprocal inductive signaling pathways essential for metanephric mesenchymal nephron branching morphogenesis will result in kidney abnormalities.
Fig.1 The
PAX2 gene is also expressed in the ureteric bud (UB). ((Muntean
et al., 2023)
Therapeutics Development for Renal Coloboma Syndrome
| Drug/Technology |
Therapeutic Target |
Key Findings/Mechanism |
Development Stage |
| Everolimus (mTOR Inhibitor) |
mTORC1 pathway |
Suppresses hyperactivated mTOR signaling to delay fibrosis |
Phase II trial design |
| Pirfenidone |
TGF-β/Smad3 pathway |
Reduces collagen deposition and glomerulosclerosis |
Preclinical validation |
| AAV-PAX2 Gene Therapy |
PAX2 haploinsufficiency |
AAV9-mediated PAX2 gene delivery to renal tubular cells |
Preclinical |
| Ramipril (ACE Inhibitor) |
Renin-angiotensin system (RAS) |
Reduces proteinuria and slows CKD progression |
Approved |
| CD80 Monoclonal Antibody |
CD80 (B7-1) protein |
Targets podocyte CD80 overexpression to reduce proteinuria |
Preclinical |
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 provider of preclinical research services dedicated to the therapeutic development of renal coloboma syndrome. We employ sophisticated disease models that recapitulate the key features, particularly the renal pathology and developmental defects, enabling mechanism-based drug discovery and development for this rare monogenic disorder.
Therapeutic Development Platforms for Renal Coloboma Syndrome
Disease Models Development for Renal Coloboma Syndrome
Protheragen offers innovative and comprehensive disease models to accelerate preclinical research on renal coloboma syndrome. Our platform integrates cell-based models, kidney organoids, and animal models. These models are crucial for studying the impact of PAX2 mutations on kidney development and function.
Cell-based & Organoid Models
- PAX2-KO HEK293 Cell Line
- Patient-Derived iPSCs
- PAX2 Reporter Cell Line
- Conditional PAX2-KO Organoid
Animal Models
- Pax2+/- Heterozygous Mice
- Zebrafish pax2a Mutants
- Conditional Pax2-KO Rats
- Humanized PAX2 Transgenics
Protheragen offers end-to-end preclinical development services tailored to renal coloboma syndrome's unique challenges. We specialize in disease model development, pharmacokinetics, and drug safety evaluation, enabling us to support your investigation from the initial stages to preclinical validation. If you are interested in our services, please don't hesitate to contact us.
References
- Muntean, C., et al. "Pax2 Gene Mutation in Pediatric Renal Disorders-a Narrative Review." Int J Mol Sci 24.16 (2023).
- Saida, K., et al. "A Novel Truncating Pax2 Mutation in a Boy with Renal Coloboma Syndrome with Focal Segmental Glomerulosclerosis Causing Rapid Progression to End-Stage Kidney Disease." CEN Case Rep 9.1 (2020): 19-23.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
