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Translational and clinical pharmacology considerations in drug repurposing for X‐linked adrenoleukodystrophy—A rare peroxisomal disorder
Author(s) -
Tieu Julianne H.,
Sahasrabudhe Siddhee A.,
Orchard Paul J.,
Cloyd James C.,
Kartha Reena V.
Publication year - 2022
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.15090
Subject(s) - medicine , drug repositioning , drug development , repurposing , drug , clinical trial , disease , pharmacology , clinical pharmacology , intensive care medicine , pharmacodynamics , adrenoleukodystrophy , population , bioinformatics , pharmacokinetics , biology , ecology , receptor , environmental health , peroxisome
X‐linked adrenoleukodystrophy (X‐ALD) is an inherited, neurodegenerative rare disease that can result in devastating symptoms of blindness, gait disturbances and spastic quadriparesis due to progressive demyelination. Typically, the disease progresses rapidly, causing death within the first decade of life. With limited treatments available, efforts to determine an effective therapy that can alter disease progression or mitigate symptoms have been undertaken for many years, particularly through drug repurposing. Repurposing has generally been guided through clinical experience and small trials. At this time, none of the drug candidates have been approved for use, which may be due, in part, to the lack of pharmacokinetic/pharmacodynamic information on the repurposed medications in the target patient population. Greater consideration for the disease pathophysiology, drug pharmacology and potential drug–target interactions, specifically at the site of action, would improve drug repurposing and facilitate drug development. Incorporating advanced translational and clinical pharmacological approaches in preclinical studies and early‐stage clinical trials will improve the success of repurposed drugs for X‐ALD as well as other rare diseases.