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Wilson's Disease

The primary therapeutic challenge in Wilson's disease is achieving lifelong copper homeostasis without causing severe iatrogenic copper deficiency or encountering the significant adverse effects associated with current chelation therapies. To address the complexities of managing Wilson's disease, Protheragen offers comprehensive support services to streamline your process from drug candidate development to market launch.

Overview of Wilson's Disease

Wilson's disease is a rare, autosomal recessive disorder of copper metabolism, representing a critical model for inborn errors of metabolism with profound neurological and hepatic consequences. The disease manifests from a failure in the homeostatic mechanisms responsible for the excretion of excess dietary copper, leading to its pathological accumulation in vital organs, primarily the liver and central nervous system. The clinical presentation is notoriously heterogeneous, often delaying diagnosis.

Pathological mechanism of Wilson's disease. Fig.1 Pathophysiology of Wilson's disease. (Seetharaman J, Sarma M S., 2021)

Pathogenesis of Wilson's Disease

Wilson's disease is an autosomal recessive disorder caused by mutations in the ATP7B gene, which encodes a copper-transporting ATPase primarily expressed in the liver. These mutations impair hepatic copper excretion into bile and its incorporation into ceruloplasmin, leading to toxic copper accumulation within hepatocytes. Subsequent oxidative stress and cellular damage result in copper release into the bloodstream, ultimately causing systemic copper deposition and tissue injury in the liver, brain, and other organs.

Schematic diagram of copper metabolism defects and the pathogenesis of Wilson's disease. Fig.2 Defective copper metabolism and pathogenesis of Wilson's disease. (Chakraborty U, Paria T K., 2021)

Therapeutic Development for Wilson's Disease

Drug Names	Mechanism of Action	Targets	NCT Number	Research Phase
VTX-801	An investigational gene therapy designed to deliver a functional copy of the ATP7B gene to liver cells (hepatocytes) to restore the body's natural ability to regulate copper.	ATP7B Protein / Hepatocytes	NCT04537377	Phase I/II
Trientine Dihydrochloride	A copper-chelating agent that binds to excess circulating copper ions to form stable complexes that are then eliminated from the body primarily through urinary excretion.	Circulating Copper Ions (Cu²⁺)	NCT01874028	Phase I
NPC-02	A small molecule pharmacological chaperone that binds to and stabilizes specific mutant forms of the ATP7B protein, promoting their correct folding and trafficking to the Golgi apparatus to restore function.	Mutant ATP7B Protein	NCT00212355	Phase III

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

As a preclinical research service provider for Wilson's disease, Protheragen provides end-to-end diagnostic and therapeutic development solutions. We excel in building physiologically relevant models, including in vitro models, animal models, and specialized blood-brain barrier (BBB) models, to enable comprehensive biomarker discovery, target validation, and CNS drug efficacy optimization.

Therapeutic Development Services

By Molecule Types

By Mechanism of Action

Disease Model Development Services

In Vitro Model Development
Patient-Derived Cell Model Development Neuronal Cell Model Development Glial Cell Model Development	Co-Culture Model Development Brain Organoid Development Spinal Cord Organoid Development
Microfluidic Model Development
Neurovascular Unit (NVU) Model Development Axon Degeneration Model Development Neuromuscular Junction (NMJ) Model Development	Neuroinflammation Model Development Synaptic Plasticity Model Development Organoid-on-a-Chip Model Development
Animal Model Development
Long-Evans Cinnamon Rat: This model possesses a natural spontaneous deletion in the Atp7b ortholog, leading to progressive hepatic copper accumulation and is renowned for closely mimicking the human disease's hepatic and neurological pathology. Toxic-milk Mouse: This model harbors a point mutation (tx mutation) in the Atp7b gene, which not only causes copper accumulation in the offspring but also results in the secretion of copper-rich, "toxic" milk from homozygous dam mothers. Atp7b Knockout Mouse: This is a genetically engineered model with a targeted disruption of the Atp7b gene, providing a well-defined and consistent platform for studying the molecular consequences of a complete lack of functional ATP7B protein. Labrador Retriever: Certain lines of this breed develop a hereditary copper toxicosis due to a mutation in a COMMD1 gene, representing a valuable large animal model for studying alternative genetic causes of pathological hepatic copper accumulation.

At Protheragen, we offer comprehensive pharmacodynamic (PD), pharmacokinetic (PK), and toxicology research services to support the development and regulatory approval of potential therapies for Wilson's disease. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.

References

Seetharaman J, Sarma M S. Chelation therapy in liver diseases of childhood: current status and response[J]. World journal of hepatology, 2021, 13(11): 1552.
Chakraborty U, Paria T K. 130 Common Metabolic Disorders: Amyloidosis, Porphyria, and Wilson's Disease[J]. 2021.

For research use only. Not intended for any clinical use.