Nail-Patella Syndrome

Nail-Patella Syndrome (NPS), also known as Hereditary Onycho-Osteodysplasia (HOOD), is a rare disorder primarily affecting the skeletal system (hypoplastic patellae and elbow dysplasia), nails, and kidneys, exhibiting an autosomal dominant pattern of inheritance. Protheragen is leveraging their knowledge of kidney disorders to develop therapies for nail-patella syndrome, addressing its multi-system complexities with focused preclinical and therapeutic design.

Introduction to Nail-Patella Syndrome

Nail- Patella syndrome has a fractional occurrence of approximately 50,000. Hereditary conditions tend to have a classic tetrad of symptoms. Iliac horns, knee caps, elbows, and nails are some of the more salient features with bony pelvic outgrowths. The severity of signs and symptoms differs within the same family. The outcome differs depending upon the severity of the condition and prognosis. 30-60% of afflicted individuals show some form of chronic kidney issues, some of which are prone to develop proteinuria and hematuria, while a mere 5-10% progress to end stage renal failure. The genetic basis of the condition and some of the mechanisms have remained unclear, with more recent publications attempting to piece them together.

Pathogenesis of Nail-Patella Syndrome

Fig.1 LMX1B protein. (Carinelli et al., 2020)

Nail-Patella Syndrome (NPS) is caused by a singular change (heterozygous) in the LMX-1B gene, which is an important transcription factor in the LMX-1B gene, associated with embryonic development, is a critical transcription factor in embryonic development. This gene's dysfunction disrupts the development of certain tissues, especially the glomerular basement membrane (GBM) of the kidneys. LMX1B is in charge of transcription of certain genes necessary for type IV collagen (one of the most important components of GBM). As a result, patients have GBM structural anomalies in form of abnormal thickening with fibrillar deposits, which alters the kidney's filtration barrier and resulting in characteristic proteinuria and hematuria. All the diverse clinical manifestations of NPS associated with the LMX1B gene defect, such as the developmental and structural changes in nails and limbs and advancing renal pathology, can be explained by this singular defect.

Therapeutic Development for Nail-Patella Syndrome

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

At Protheragen, we are dedicated to advancing the understanding and potential therapeutic avenues for complex genetic kidney disorders like nail-patella syndrome. We offer comprehensive preclinical therapeutic development services, specializing in creating advanced disease models. Our focus is on elucidating the diverse genetic and developmental impacts of LMX1B gene mutations that lead to the multi-systemic manifestations of NPS, with a particular emphasis on the mechanisms underlying NPS nephropathy.

Therapeutic Development Platform for Nail-Patella Syndrome

Protheragen combines deep expertise in developmental biology, rare genetic disorders, and renal pathology with advanced molecular and cellular technologies to address the multifaceted mechanisms leading to Nail-Patella Syndrome. Our comprehensive platform supports the development of various therapeutic modalities:

Disease Models Development for Nail-Patella Syndrome

Developing innovative and comprehensive disease models is central to advancing preclinical research for Nail-Patella Syndrome. Our integrated platform effectively captures the LMX1B dysfunction and developmental defects that cause NPS, supporting extensive drug discovery and mechanism-based investigations focused on multi-organ development and pathology.

Cell-based & Organoid Models

• NPS Patient iPSC Line
• Isogenic Control iPSC Line
• NPS Patient iPSC-Derived Podocytes
• Isogenic Control iPSC-Derived Podocytes
• NPS Patient iPSC-Derived Kidney Organoid

Animal Models Development

• Podocyte-specific Lmx1b Knockout Mouse
• Nphs1-Cre; Lmx1b^flox/flox Mouse
• Lmx1b point mutation mouse model
• lmx1bb Knockdown Zebrafish
• lmx1bb Mutant Zebrafish

Drug Pharmacokinetics & Safety Evaluation Services

Protheragen offers integrated preclinical development solutions specifically designed for research in kidney disorders like Nail-Patella Syndrome. Our expertise in disease model development, pharmacokinetics, and drug safety evaluation allows us to support your investigation from the initial stages to preclinical validation.

If you are interested in our services and advancing research for Nail-Patella syndrome, please don't hesitate to contact us.

References

1. Leung, L. T., et al. "Novel Lmx1b Variants in Nail-Patella Syndrome." Hong Kong Med J 31.1 (2025): 75-77.
2. Najafian, B., et al. "Ajkd Atlas of Renal Pathology: Nail-Patella Syndrome-Associated Nephropathy." Am J Kidney Dis 70.4 (2017): e19-e20.

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