Nephronophthisis

Nephronophthisis (NPHP) is an early-onset autosomal recessive ciliopathy, standing as the foremost genetic factor leading to end-stage renal disease (ESRD) in children and adolescents. Protheragen is focused on developing therapeutic intervention for rare kidney disorders. Here, we provide our tailored service solutions for nephronophthisis.

Overview of Nephronophthisis

NPHP is classified under rare disorders and is chronic in nature. It is inherited in an autosomal recessive pattern and is marked by the progressive loss of nephrons. It often leads to polycystic kidney disease and is referred to as precursor kidney disease. It is also the leading cause of ESRD among the youth. Those afflicted will experience an increase in urine production, increased thirst, and extreme fatigue. Infantile, juvenile, and adolescent forms of NPHP are characterized based on the age of ESRD onset. NPHP mainly affects the kidney, but also the retina and are part of a larger group of diseases known as ciliopathies which involve other parts of the body such as the brain and the liver.

Pathogenesis of Nephronophthisis

Ciliopathy can be characterized as the malfunction of primary cilia, which constitutes the leading factor in Nephronophthisis. More than twenty genes, NPHP1-NPHP20, have been cataloged, with mutations in NPHP genes causing the dysfunction of primary cilia or centrosome of renal epithelial cells. Primary cilia are minute, hair-like organelles that extend from the surface of the cell and serve as cellular antennae which are important in receiving and transducing multiple kidney signals required for the organ's development, maintenance, and function.

Fig.1 Multi-organ involvement in Nephronophthisis (NPHP) presentation. (Wolf et al., 2021)

Disruption of ciliary function in NPHP leads to impairment in cell communication and signaling of the cells which informs the body of the abnormal renal tubule formation, tubular atrophy, scaling and thick or thin tubular basement membranes, and cyst formation, which is common at the corticomedullary junction. Ongoing inflammation and scarring advances these stages which contributes to the permanent destruction of kidney function. Multi-organ involvement or some NPHP-associated syndromes can also and is, in some cases, explained due to the critical presence and function of cilia that are omnipresent in various cell types in the body.

Therapeutics Development for Nephronophthisis

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 nephronophthisis and offers comprehensive preclinical therapeutic development services. We focus on understanding the diverse genetic and ciliary impacts that lead to NPHP.

Therapeutic Development Platforms for Nephronophthisis

• Small Molecule Drug
• Cell Therapy
• Gene Therapy

• Therapeutic Antibody
• Therapeutic Peptide
• Therapeutic Protein

Disease Models Development for Nephronophthisis

Protheragen offers innovative and comprehensive disease models to advance the preclinical research of nephronophthisis. Our platform integrates cell-based models, kidney organoids, and animal models to effectively capture the ciliary dysfunction and progressive tubulointerstitial damage that cause NPHP.

Cell-based & Organoid Models

• NPHP1-KO Human Tubular Epithelial Cells
• CEP290 p.R1664W Mutant Podocyte Lines
• 3D Cystic Organoids
• Cilia-deficient Tubuloid-Fibroblast Co-Cultures

Animal Models

• Nphp4^Δex9knockout mice
• Jck (Nphp9) zebrafish model
• Nphp3^-/-rats with retinal degeneration
• Human renal cyst xenografts in NSG mice
• FAN1^L343Rknock-in 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

In Vivo Pharmacokinetics Services

• PK Studies in Renal Impairment Models
• Kidney Tissue Distribution Study
• Blood-to-Plasma Ratio
• Metabolite Profiling

Drug Safety Evaluation

• General Toxicology Evaluation
• Genetic Toxicology Evaluation
• Developmental and Reproductive Toxicity Evaluation

• Immunogenicity and Immunotoxicity Evaluation
• Local Toxicity Evaluation
• Phototoxicity Evaluation

• Tissue Cross-Reactivity Evaluation
• Safety Pharmacology Evaluation
• Toxicokinetic Evaluation

Protheragen provides integrated preclinical development solutions specifically designed for research in rare genetic kidney disorders like nephronophthisis. 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

1. Gupta, S., J. E. Ozimek-Kulik, and J. K. Phillips. "Nephronophthisis-Pathobiology and Molecular Pathogenesis of a Rare Kidney Genetic Disease." Genes (Basel) 12.11 (2021).
2. Wolf, M. T. F., et al. "Nephronophthisis: A Pathological and Genetic Perspective." Pediatr Nephrol 39.7 (2024): 1977-2000.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.