Targeting liver nuclear receptors as a treatment for Wilsons disease

Wilson disease is a hepato-neurologic disorder caused by mutations in the gene ATP7B and accumulation of copper in tissues, predominantly in the liver. The disease is lethal, unless treated. Current life-long treatment involves copper chelation or copper replacement using Zn. Both procedures alleviate major symptoms but side effects are frequent and neurologic deterioration is often observed. Using Atp7b-/- mice (an animal model for Wilson disease), we demonstrated that treatment of these animals (via addition to the diet) with a specific compound markedly improves their liver function ameliorating major symptoms of the disease. Targeting nuclear receptors in Wilson disease represents an entirely new approach to treatment, which can potentially supplement, or be used as a alternative to treatment using copper chelators. Targeting nuclear receptor can be beneficial in a case of side effects (commonly observed in Wilsons disease) or during preparation for liver transplant

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