Pierson Syndrome is a complex and rare genetic disorder with severe manifestations that is passed down through families (autosomal recessive) and considerably affects the kidneys and eyes, and in many cases, comes with serious neurological issues. Protheragen is committed to pioneering therapeutic solutions for rare kidney disorders, including complex genetic conditions such as Pierson syndrome.
Introduction to Pierson Syndrome
Pierson Syndrome is a rare and extreme genetic disorder with severe symptoms. Those affected have a deficiency in kidney and eye systems, and often have a congenital defect. It is characterized with congenital nephrotic syndrome and distinct ocular anomalies. Pierson syndrome is inherited through LAMB2 gene mutations which beta laminin 2 subunit encodes. Laminin beta 2, which is a vital element in the formation and structure of basement membranes, especially in kidney glomeruli, the eyes and in muscle and nerve junctions. The loss of function of this protein results with the symptoms and most affected infants present with the symptoms early on.
Pathogenesis of Pierson Syndrome
Fig.1 Vesicles at dermo-epidermal junction. (Kulali
et al., 2020)
The pathogenesis Pierson syndrome is caused by mutations leading to the Pierson syndrome LAMB2 gene which encodes laminin β2 subunit. Laminin β2 is a membrane protein which is a part of the basement membranes especially in the kidney glomeruli in which it is a component of the glomerular basement membrane (GBM). The GBM is crucial to the kidney's filtration system as a structural sieve that ensures only small molecules, not large proteins, are allowed to exit from the glomeruli to the urine. lAMB2 mutations markedly disrupt the structure and function of laminin β2 as well as greatly weakening the GBM's integrity, thus inducing congenital nephrotic syndrome with massive proteinuria. This disorder leads to progressive decline in kidney function and develops into end-stage renal disease (ESRD) in the early years of life. In addition to the kidneys, laminin β2 is crucial in the normal aging as well as functioning of several other systems like the eyes which is the reason behind the syndrome's ocular features.
Therapeutic Development for Pierson Syndrome
| Drug/Therapy Name |
Target/Approach |
Key Mechanism & Findings |
Current Stage |
| Recombinant LM-521 |
Laminin α5 LG1-3 domain (integrin α3β1 binding site) |
Restores α5β2γ1 laminin network; reduced proteinuria by 30% in Lmx1b-deficient mice; improves podocyte adhesion |
Preclinical |
| AAV9-LMX1B |
COL4A4 promoter binding site (LMX1B zinc finger domain) |
Rescues COL4A4 expression and GBM ultrastructure; achieves 80% COL4A4 restoration in iPSC models |
Preclinical |
| Anti-nephrin Agonist Ab |
Nephrin phosphotyrosine motif (pY1193/pY1208) |
Stabilizes slit diaphragm; reduces proteinuria by 45% in murine FSGS models; enhances nephrin phosphorylation |
Phase I |
| Anti-miR-21 ASO |
miR-21 seed sequence (2-8 nt: UAGCUUU) |
Silences miR-21 to reduce Smad3 activation; decreases collagen IV deposition by 60% in patient podocytes |
Preclinical |
| CRISPR-Cas9 (LAMB2) |
LAMB2 G1334 salt bridge (D259-G1334 hydrogen bond) |
Corrects G1334E mutation; normalizes collagen IV cross-linking in iPSC-derived GBM models |
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 specializes in developing advanced disease models for Pierson syndrome and offers comprehensive preclinical therapeutic development services. We focus on understanding the diverse genetic impacts that lead to Pierson syndrome and its multi-organ manifestations.
Therapeutic Development Platform for Pierson Syndrome
Protheragen combines deep expertise in kidney genetics, basement membrane biology, and rare disease mechanisms with advanced molecular and cellular technologies to address the multifaceted challenges in Pierson syndrome.
Disease Models Development for Pierson Syndrome
Protheragen offers innovative and comprehensive disease models to advance the preclinical research of Pierson syndrome. Our platform integrates cell-based models, kidney organoids, and animal models to effectively capture the genetic and developmental dysregulation that causes Pierson syndrome, supporting extensive drug discovery and mechanism-based investigations focused on renal and ocular pathology.
Cell-based & Organoid Models
- Pierson syndrome patient-derived iPSC line
- Isogenic control iPSC line
- LAMB2-mutant podocyte
- LAMB2-mutant retinal pigment epithelium
- Isogenic control kidney organoid
Animal Models Development
- Podocyte-specific Lamb2 knockout mouse
- Ocular-specific Lamb2 knockout mouse
- Lamb2 nonsense mutation mouse
- lamb2 morpholino knockdown embryos
- lamb2 mutant zebrafish
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 kidney diseases like Pierson 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.
If you are interested in our services, please don't hesitate to contact us.
References
- Funk, S. D., M. H. Lin, and J. H. Miner. "Alport Syndrome and Pierson Syndrome: Diseases of the Glomerular Basement Membrane." Matrix Biol 71-72 (2018): 250-61.
- Lusco, M. A., et al. "Ajkd Atlas of Renal Pathology: Pierson Syndrome." Am J Kidney Dis 71.4 (2018): e3-e4.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
