Translational and clinical pharmacology considerations in drug repurposing for X-linked adrenoleukodystrophy-A rare peroxisomal disorder.

Autor:	Tieu JH; Center for Orphan Drug Research, Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA., Sahasrabudhe SA; Center for Orphan Drug Research, Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA., Orchard PJ; Division of Pediatric Blood and Marrow Transplantation, Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, Minnesota, USA., Cloyd JC; Center for Orphan Drug Research, Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA., Kartha RV; Center for Orphan Drug Research, Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
Jazyk:	angličtina
Zdroj:	British journal of clinical pharmacology [Br J Clin Pharmacol] 2022 Jun; Vol. 88 (6), pp. 2552-2563. Date of Electronic Publication: 2021 Oct 21.
DOI:	10.1111/bcp.15090
Abstrakt:	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. (© 2021 British Pharmacological Society.)
Databáze:	MEDLINE
Externí odkaz:	Plný text