Title:Repurposed Drugs in Metabolic Disorders
Volume: 13
Issue: 18
Author(s): Josef Finsterer and Marlies Frank
Affiliation:
Keywords:
Metabolic disorders, metabolism, repurposing, new indication, reprofiling, retasking, drug development.
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.