WAGR syndrome is an unusual genetic condition defined by a contiguous gene deletion on chromosome 11p13, which results in a predisposition for aniridia, genitourinary abnormalities, intellectual disability, and most notably, Wilms tumor. Protheragen is dedicated to advancing therapeutic solutions for rare kidney disorders, including WAGR syndrome, by providing a complete suite of services from disease modeling to preclinical therapeutic development.
Introduction to WAGR Syndrome
WAGR syndrome's prevalence is estimated as 1 in 500,000 to 1 million live births. It is commonly the result of a deletion of a segment on the short arm of chromosome 11 (11p13) which is known to house important genes such as WT1 and PAX6. This deletion ranges in size which results in variability in the clinical features and the severity of the condition. As with many chronic conditions, the disease progresses with time. WAGR syndrome is marked with renal complications, a slightly higher risk of WIlms tumor in childhood, followed by a more advanced stage of chronic kidney disease.
Fig.1 Multicolor banding (MCB) analysis are evaluated by hybridization profiles of corresponding fluorochromes (Marakhonov
et al., 2023)
Pathogenesis of WAGR Syndrome
The WAGR syndrome arises from a contiguous gene deletion at chromosome 11p13, most often involving the WT1 (Wilms Tumor 1) and PAX6 (Paired Box 6) genes. The WT1 gene, which is a haploinsufficient tumor suppressor associated with renal and genitourinary tract development, markedly increases the chance of a malignant kidney cancer often diagnosed in children, known as Wilms tumor, alongside several genitourinary abnormalities. In addition to the tumor, a person with WT1 deficiency is at risk of developing progressive chronic kidney disease, including focal segmental glomerulosclerosis (FSGS) kidney disease. In addition, the deletion of the PAX6 gene, which is a master regulator of eye development, results in the disorder of aniridia and other eye disorders. While the boundaries of the deletion can be variable, it is also possible that the deletion can affect other genes such as BDNF which would account for some of the diverse neurological and metabolic manifestations of the syndrome. These important genes are often critical for the development of several systems. The loss of these genes can therefore lead to the WAGR syndrome developmental disorder.
Therapeutics Development for WAGR Syndrome
| Drug/Technology |
Therapeutic Target |
Key Findings/Mechanism |
Development Stage |
| AAV9-PAX6/WT1 Therapy |
PAX6/WT1 genes |
Delivers functional PAX6/WT1 genes; mouse models show corneal epithelial repair and reduced proteinuria |
Preclinical |
| CRISPR-Cas9 Repair |
WT1 gene |
Restores WT1 function in patient iPSC podocytes in vitro; corrects DNA-binding defects |
Preclinical |
| HSCT Combination Therapy |
/ |
Sequential HSCT before kidney transplant increases graft survival; promotes immune tolerance |
Phase II |
| Recombinant BDNF |
BDNF deficiency |
Nasal administration improves obesity and hyperphagia in animal models; regulates hypothalamic signaling |
Preclinical |
| Exon-Skipping ASOs |
PAX6 pre-mRNA |
Corrects aberrant PAX6 mRNA processing; restores functional transcription factor activity |
IND-enabling |
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 specializes in developing advanced disease models for WAGR syndrome and offers comprehensive preclinical therapeutic development services. We focus on understanding the diverse genetic impacts that lead to WAGR syndrome and its multi-systemic manifestations.
Therapeutic Development Platforms for WAGR Syndrome
Disease Models Development for WAGR Syndrome
Protheragen offers innovative and comprehensive disease models to advance the preclinical research of WAGR syndrome. Our platform integrates cell-based models, kidney organoids, and animal models to effectively capture the developmental defects and disease progression that cause WAGR syndrome, supporting extensive drug discovery and mechanism-based investigations focused on renal, ocular, and neurological pathologies.
- WT1/PAX6-deficient podocyte
- PAX6-deficient retinal cell
- Neural progenitor
- WAGR patient-derived kidney organoid
- WAGR patient-derived retinal organoid
- Kidney-specific WT1 deletion mouse
- Eye-specific PAX6 deletion mouse
- Neural WT1/PAX6 dual KO mouse
- Chromosome 11p13 microdeletion mouse
- wt1/pax6a morpholino knockdown zebrafish
- Alms1-mutant rabbits
Drug Pharmacokinetics & Safety Evaluation Services
In Vitro ADME Services
- Renal Clearance Assay
- Drug-Transporter Interaction Screening
- Metabolic Stability Assay
- CYP Inhibition Screening
- Plasma Protein Binding
Protheragen provides integrated preclinical development solutions specifically designed for research in disorders like WAGR syndrome. We specialize in disease model development, pharmacokinetics, and drug safety evaluation, enabling us to support your investigation from the initial stages to preclinical validation.
Contact us today to accelerate your WAGR syndrome research with end-to-end solutions.
References
- Marakhonov, A. V., et al. "Complex Chromosomal Rearrangement Involving Chromosomes 10 and 11, Accompanied by Two Adjacent 11p14.1p13 and 11p13p12 Deletions, Identified in a Patient with Wagr Syndrome." Int J Mol Sci 24.23 (2023).
- Yaga, T., et al. "Potocki-Shaffer Syndrome Revealed in a Wagr Syndrome Case with Multiple Exostoses." Pediatr Int 65.1 (2023): e15405.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
