Perspectives for gene therapy of Wilson disease.

Wilson disease is a rare autosomal-recessive copper overload disorder due to mutations of the Wilson disease gene ATP7B. The disease typically manifests at late childhood or in young adults with hepatic and/or neurological symptoms. Being fatal without medical treatment or liver transplantation the long-term outcome of Wilson disease depends on the adherence to an effective treatment. Because current medical treatment options are not effective in all Wilson disease patients and adherence to therapy is a problem, gene therapy might represent an alternative curative future therapy. In the rat model of Wilson disease adenoviral and lentiviral gene transfer studies could prove that viral gene transfer is therapeutically effective and can reverse clinical symptoms. However, both approaches were limited by a more or less transient transgene expression. As several tactics can be used to overcome these current limitations, gene therapy approaches may become more efficient than standard medical treatment for Wilson disease in the future. This review discusses both, existing vectors and strategies and prospective developments towards liver-directed gene therapy, although there is still a long way to go until gene therapy can be used for safe treatment of Wilson disease in humans.