Current Pharmaceutical Design vol:17 issue:24 pages:2550-2557
There are numerous inborn errors of metabolism of the liver, and they are all rare to very rare. To get a clear picture of the indications for gene transfer in these conditions, it is essential to get a clear view on the current (lack of) insight in the pathophysiology of these disorders, the current treatment options and hence on the window of opportunity for new treatments as gene transfer. The aim of this review, is to illustrate the problems related to treatment of inborn errors of metabolism of the liver. General aspects defining the quest for treatments for very rare diseases are touched upon, but for the sake of clarity, this review is restricted to five illustrative examples: Crigler-Najjar type I, the urea cycle defects, phenylketonuria, classic galactosemia and propionic acidemia. These examples reflect the problems that are currently experienced and can be expected, when gene transfer trials for these disorders are undertaken.