Induced Pluripotent Stem Cells for the Development of Novel Drug Therapies for Hepatic and Neurological Wilson Disease

Wilson disease (WD) is caused by a defective gene for a copper-transporting protein that regulates cellular copper homeostasis in all major organs. Copper is an essential metal ion that is required for physiological cell functions (e.g. numerous enzymes require copper as a co-factor). It often occurs in people without a known family history of the condition.

The condition affects females and males likewise. Wilson disease occurs in approximately 1 out of every 30,000 births and belongs to the class of rare diseases. Because this is an inherited disorder, risks include a family history of Wilson disease.

Symptoms most often appear during adolescence or early adulthood. Symptoms may include:

increased thickness of the interventricular septum and left ventricular posterior wall supraventricular tachycardias tremors in hands, legs, head repetitive muscle contractions (dystonia) renal stones renal failure psychiatric symptoms (e.g. depression) liver disease

Therapeutic approaches include the drug Penicillamine, which binds to accumulated copper and eliminate it through urine. However, its use is controversy, since it is associated with an extended range of adverse effects and patients with neurologic manifestations deteriorated throughout the use of Penicillamine. Another strategy is the use of zinc salts that function via a detoxification effect of the stored copper ions. Recent studies suggested that zinc salts are effective in presymptomatic Wilson disease, but are problematic in hepatic Wilson disease and not suitable as a monotherapy.