Autosomal Recessive Polycystic Kidney Disease (ARPKD)

Autosomal recessive polycystic kidney disease (ARPKD) is a severe life-threatening monogenic disorder with insidious clinical onset manifesting predominantly in the kidneys and liver due to PKHD1 gene mutations. Protheragen offers preclinical ARPKD research and combined therapy methods through integrated multi-disciplinary service designs to solve overarching ADPKD research and therapy issues.

Introduction to ARPKD

Described in the medical literature decades ago, Autosomal Recessive Polycystic Kidney Disease (ARPKD) is an exceedingly infrequent condition that develops due to genetic anomalies of the PKHD1 gene on chromosome 6, and results into kidney cyct formation alongside potential liver, pancreas, and other organ involvement. In contrast to other polycystic kidney diseases that emerge later in life, ARPKD is an infancy- or childhood-onset condition with high morbidity.

Pathogenesis of ARPKD

ARPKD is a ciliopathy caused by biallelic mutations of the PKHD1 gene which encodes fibrocystin/polyductin (FPC). FPC is a large integral membrane protein found in primary cilia, renal collecting ducts, and bile ducts. The loss of functional FPC (or fibrocystin) inhibits critical signaling pathways regulated by primary cilia, such as the Wnt, Hedgehog, and mTOR pathways which eventually leads to abnormal cell proliferation, fluid secretion, and fibrotic activity in the kidney and liver. This culminates in the characteristic cyst formation, progressive renal failure, and hepatobiliary complications Associated with the condition.

Fig.1 A schematic diagram of the protein structure of Fibrocystin (FPC) and DZIP1L, including an illustration of their most common expression local isation in the cell. (Goggolidou and Richards, 2022)

Therapeutics Development for ARPKD

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 leading preclinical service provider dedicated to advancing the understanding and potential therapeutic avenues for ARPKD. Our extensive expertise in renal and genetic disorders, combined with sophisticated disease models and diverse therapeutic development platforms, enables us to support groundbreaking research into its underlying mechanisms and associated systemic conditions.

Therapeutic Development Platforms for ARPKD

• Small Molecule Drug
• Cell Therapy
• Gene Therapy

• Therapeutic Antibody
• Therapeutic Peptide
• Therapeutic Protein

Disease Models Development for ARPKD

Protheragen provides cutting-edge and comprehensive disease models to accelerate preclinical research into ARPKD. Our platform integrates cell-based models, kidney organoids, and animal models to effectively mirror the genetic and developmental characteristics of this complex syndrome.

Cell-based & Organoid Models

• ARPKD patient-derived kidney epithelial cell lines
• Mouse inner medullary collecting duct (mIMCD) cells
• Mouse kidney organoids with Pkhd1 knockout
• ARPKD patient-derived cholangiocyte models

Animal Models

• Pkhd1-mutant mouse models
• Pkhd1 conditional knockout mouse models
• Pkhd1-deficient rat models
• Zebrafish pkhd1 mutant lines
• Congenital polycystic kidney disease (PCK) rat model

Protheragen's integrated preclinical development solutions are specifically designed for research in rare kidney diseases, such as ARPKD. We specialize in custom disease model development, pharmacokinetics, and drug safety evaluation, enabling unparalleled support for your investigation.

Contact us today to accelerate your ARPKD research with end-to-end solutions.

References

1. Cordido, A., M. Vizoso-Gonzalez, and M. A. Garcia-Gonzalez. "Molecular Pathophysiology of Autosomal Recessive Polycystic Kidney Disease." Int J Mol Sci 22.12 (2021).
2. Goggolidou, P., and T. Richards. "The Genetics of Autosomal Recessive Polycystic Kidney Disease (Arpkd)." Biochim Biophys Acta Mol Basis Dis 1868.4 (2022): 166348.

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