Chapter 19 - Novel perspectives on Wilson disease treatment

Abstract

Wilson disease is an autosomal-recessive copper overload disorder causing hepatic and neurologic symptoms. Commonly used medical therapy shows satisfactory results with regard to hepatic disease but only limited effects in neurologically affected patients. In recent years several new therapy options have been developed, showing promising results that might improve the management of Wilson disease in the near future. Optimization of treatment regimens depending on biochemical response pattern seems worthwhile, especially in the decoppering phase of therapy. The chelator tetrathiomolybdate (TTM) is a promising therapy option, currently under clinical investigation. TTM is a fast-acting and very potent chelator and appears to be associated with early neurologic deterioration after initiation of therapy to a lower extent than the drugs currently used. Treatment with nonchelating drugs characterized by alternative modes of action is under investigation, but restricted to animal or in vitro studies to date. This includes basic research studies demonstrating proof of principle for successful cell or gene therapy in Wilson disease in order to restore sufficient biliary copper excretion, even before the onset of disease.