Repurposed Drugs in Metabolic Disorders

Abstract

Drug repurposing (drug repositioning, drug reprofiling, drug retasking) gains increasing importance as the development of new drugs becomes increasingly expensive. Though only a few compounds have been approved for new indications in the field of metabolic disorders, there are a number of substances which have the potential to become reprofiled in a new indication. Generally, reprofiled drugs for metabolic disorders can be classified in three groups. Group A contains those of which both, the original and repurposed indication, concern metabolic disorders. Group B comprises drugs, which were originally approved for non-metabolic disorders but show beneficial effects for metabolic disorders after repurposing. Group C comprises drugs, which were originally approved for metabolic disorders and are effective for non-metabolic disorders in their repurposed indication. Repurposed drugs in the field of metabolic disorders of group A include tetra-hydrobiopterin, originally indicated for phenylketonuria and now also approved for tetrahydrobiopterindeficiency, coenzyme-Q, originally approved for primary coenzyme-Q deficiency and reprofiled for statin-myopathy, and colesevelam, originally approved to reduce elevated low-density lipoprotein (LDL)-cholesterol (LDL-C) and now being approved for type-2-diabetes. An example of group C is phenylbutyrate, which was originally approved for urea-cycle disorders and meanwhile gained approval for progressive familial intrahepatic cholestasis type 2 due to mutations in the ABCB11 gene. Still additional compounds used to treat metabolic (non-metabolic) disorders show promising effects in non-metabolic (metabolic disorders) after repurposing in cell and tissue models. Future investigations will need to identify which candidate drugs may leave the pipeline status to acquire approval for new indications.