Wilson Disease
Wilson disease also referred to as hepatolenticular degeneration, stands as a rare genetic disorder characterized by the excessive accumulation of copper in various organs, with a primary impact on the liver and brain. In the realm of rare diseases, our company has established itself as a leader, specializing in providing a wide array of resources and support for researchers and scientists dedicated to studying conditions such as Wilson disease.
Overview of Wilson Disease
Wilson disease is an autosomal recessive disorder, with an incidence rate ranging from approximately 1 to 9 cases per 100,000 individuals. The condition primarily affects the liver and brain, manifesting through disrupted copper excretion mechanisms in the liver, leading to systemic copper toxicity. This excess copper not only damages crucial organs such as the liver but also interferes with neurotransmitter balance in the brain, resulting in a spectrum of neurological symptoms.
Fig.1 Cu homeostasis in liver. (Dev, S., et al., 2022)Pathogenesis of Wilson Disease
Central to the pathogenesis of Wilson disease is a mutation in the ATP7B gene, crucial for copper transportation and utilization. This mutation impairs the incorporation of copper into essential proteins and disrupts its excretion, triggering the accumulation of free copper in tissues. Wilson disease presents a diverse array of mutations within ATP7B, comprising missense, nonsense, insertions, deletions, and rare splice site variations, underscoring the complexity of this genetic disorder.
Fig.2 Summary of main pathologic changes in Wilson disease liver. (Dev, S., et al., 2022)
Therapeutics Development of Wilson Disease
| Types | Drug Names | Mechanism of Action | Targets | Research Phase |
|---|---|---|---|---|
| Cu chelation | D-penicillamine | Advance the urinary excretion of copper | Copper | Approved |
| Trientine | Promote urinary excretion of copper | Copper | Approved | |
| Tetrathiomolybdate | A strong de-coppering medication | Copper | Phase III trials | |
| Inhibitors | T0901317 | LXR agonist | LXR | Preclinical research |
| Gene therapy | AAV vectors | Correct Atp7b in hepatocytes | ATP7B | Phase I/II trials |
| Lentiviruses | Reduce the Cu content in hepatic | ATP7B | Preclinical research | |
| CRISPR-mediated correction | Correct the defect of ATP7B | ATP7B | Preclinical research |
Our Services
Our expertise and in-depth understanding of Wilson disease enable us to offer tailored solutions and support throughout the research process. Leveraging animal models and therapeutic development platforms, we aim to unravel the pathogenesis of Wilson disease, elucidate copper metabolism abnormalities, and explore potential therapeutic avenues.
Therapeutics Development Platforms
Animal Models of Wilson Disease
Animal models play a crucial role in understanding the pathogenesis of Wilson disease and developing potential therapeutic interventions. Our company offers a variety of animal models for you to provide valuable insights into the pathogenesis of Wilson disease, copper metabolism, and possible therapeutic approaches.
In the case of Wilson disease, animal models are available with spontaneous mutations that exhibit features resembling aspects of the disease.
Optional Models: LEC rat model; Toxic-milk mouse models, etc.
Genetic engineering models involve the genetic modification of animals to targeted disruption or knockout of the ATP7B gene.
Optional Models: Atp7btx model; Atp7btm1Tcg model, etc.
Why Choose Us
With our state-of-the-art facilities and cutting-edge technologies, we provide comprehensive services such as pharmacokinetic studies and drug safety evaluations, catering to the diverse needs of researchers.
To embark on a journey of collaboration and exploration, connecting with our team promises a synergistic blend of expertise and resources, propelling your research toward success.
References
- Dev, Som et al. "Wilson Disease: Update on Pathophysiology and Treatment." Frontiers in cell and developmental biology 10 (2022): 871877.
- Reed, Emily et al. "Animal models of Wilson disease." Journal of neurochemistry 146.4 (2018): 356-373.
- Kasztelan-Szczerbinska, Beata, and Halina Cichoz-Lach. "Wilson's Disease: An Update on the Diagnostic Workup and Management." Journal of clinical medicine 10.21 (2021): 5097.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.