Pharmacodynamic profiling in three patients with molybdenum cofactor deficiency type A reveals prolonged biological effects after withdrawal of cyclic pyranopterin monophosphate.

Autor: Schwahn BC; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Health Innovation Manchester, Manchester, UK. Electronic address: Bernd.schwahn@mft.nhs.uk., Barvíková K; Department of Pediatrics and Inherited Metabolic Disorders, Charles University-First Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic., Wu HT; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Health Innovation Manchester, Manchester, UK., Horman A; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Health Innovation Manchester, Manchester, UK; Department of Chemical Pathology, Great Ormond Street Hospital, London, UK., Emmett E; Biochemical Sciences, Synnovis, Guys & St Thomas' NHS Foundation Trust, London, UK., Kožich V; Department of Pediatrics and Inherited Metabolic Disorders, Charles University-First Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic.
Jazyk: angličtina
Zdroj: Molecular genetics and metabolism [Mol Genet Metab] 2024 Sep-Oct; Vol. 143 (1-2), pp. 108563. Date of Electronic Publication: 2024 Aug 10.
DOI: 10.1016/j.ymgme.2024.108563
Abstrakt: Molybdenum cofactor deficiency type A has successfully been treated in a small number of children with daily intravenous administration of cyclic pyranopterin monophosphate. Pharmacodynamic data for this novel treatment have not been published and alternative dosing intervals have not been explored. We monitored pharmacodynamic biomarkers of sulfite oxidase and xanthine oxidoreductase activity in three patients with MoCD-A for a period of 2 to 9 months after discontinuation of cPMP substitution. We found that the clinical and metabolic effects were sustained for longer than expected, over 7 days at least. Our data implicate a biological half-life of the molybdenum cofactor dependent enzyme activities of approximately 3 days and suggest the possibility that less frequent than once daily dosing intervals could be a safe alternative to current practice.
Competing Interests: Declaration of competing interest BCS was principal investigator for clinical trials sponsored by Alexion Pharma International, and Origin Biosciences Inc. He reports a personal fee for attendance at an Advisory Board meeting and an unconditional educational grant from Origin Biosciences Inc. KB, HTW, AH, EE and VK have no conflict of interests to report. cPMP for the treatment of patients was provided free of charge on compassionate grounds from Colbourne Pharmaceuticals GmbH and Origin BioSciences Inc., respectively.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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