Abstract:
Introduction: Heavy metal ions, especially copper and iron play very important roles in the pathogenesis of neurodevelopmental and neurodegenerative diseases including bilirubin-induced neurologic dysfuction (BIND), retinopathy of prematurity (ROP) and - may be - autism spectrum disorder (ASD). In addition, the copper metabolism in Wilson's disease and in newborn infants is strikingly similar. Both have large quantities of copper in the liver and brain which is contrasted by an unusually low ceruloplasmin level in the blood.
Purpose: It is a "new" drug approval for 2019: D-penicillamine (D-PA) which can administer intravenously. The most effective IV preparation of this orphan drug now is not available in the drug market.
Methods: The author analyzed the literature and incorporated the own clinical experiences which are more than 40 years. In the mean time, our studies were replicated in other institutes in Hungary, Poland, the US, India and Mexico. It is important to note that there was no intolerance or short- or long-term toxicity of the medication, in spite of the fact that D-PA was used 10-20 times higher doses in the newborn period, than those in adult.
Conclusion: To the new concept, the BIND, ROP and ASD are neurodegenerative and neurodevelopmental diseases (NDs) of immature brain caused by accumulation of free metals, unconjugated bilirubin (UCB), and UCB-Cu complex (as prooxidant), respectively, in the basal ganglia (BG) and other parts of the central nervous system (CNS). The main factor is the hemolysis of neonatal red blood cells. This process is going with the induction of a great amount of heavy metals (mainly copper and iron) and producing reactive oxygen species (ROS). These elements are circulating in the bloodstream, and pass through the immature blood-brain-barrier (BBB), finding entrance into the CNS. In addition, ROS contribute to increased BBB permeability creating a dangerous vitious circle in the neonatal brain. The intravenously administered D-PA would be effective to prevent of these processes.
