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Schwarz, Guenter ORCID: 0000-0002-2118-9338, Basel, Donald G., Schwahn, Bernd C., Spiegel, Ronen, Wong, Flora Y., Bliss, Robin and Squires, Liza (2025). Increased Survival in Patients With Molybdenum Cofactor Deficiency Type A Treated With Cyclic Pyranopterin Monophosphate. Journal of Inherited Metabolic Disease, 48 (2). pp. 1-11. Wiley. ISSN 0141-8955

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Abstract

[Artikel-Nr. e70000] Molybdenum cofactor deficiency (MoCD) Type A is an ultrarare disorder causing neurodegeneration and early death. Cyclic pyranopterin monophosphate (cPMP), a molybdenum cofactor precursor, is a therapeutic option for patients with MoCD Type A. In this study, efficacy in patients with MoCD Type A treated with recombinant cPMP (rcPMP) and/or fosdenopterin, a synthetic form of cPMP, from one retrospective and two prospective open‐label studies ( N = 14), was compared with a retrospective/prospective natural history study (untreated; N = 37). Safety was evaluated in treated patients. Patients treated with fosdenopterin/rcPMP had significantly reduced risk of premature/early death versus untreated patients (Cox proportional hazards 5.1; 95% CI 1.32–19.36; p = 0.01). MoCD disease biomarkers of urinary S‐sulfocysteine and xanthine returned to near‐normal from baseline to last visit in treated patients but remained abnormal in untreated patients. At 12 months, in treated patients, 43% could sit unassisted, 44% were ambulatory, and 57% could feed orally. Initiating fosdenopterin/rcPMP treatment ≤ 14 days after birth appeared to result in better clinical outcomes than initiating > 14 days after birth. Most patients (13/14) had a treatment‐emergent adverse event; most were unrelated to fosdenopterin/rcPMP, were mild to moderate in severity, and none led to treatment discontinuation. These results demonstrate that patients with MoCD Type A who received fosdenopterin/rcPMP versus untreated patients were more likely to survive. Some treated patients were able to feed orally and achieve developmental milestones including walking. Fosdenopterin/rcPMP was generally well‐tolerated. Improved outcomes in patients treated early support the importance of identifying MoCD in neonates and initiating treatment as soon as possible.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Schwarz, Guenter UNSPECIFIED https://orcid.org/0000-0002-2118-9338 UNSPECIFIED Basel, Donald G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwahn, Bernd C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Spiegel, Ronen UNSPECIFIED UNSPECIFIED UNSPECIFIED Wong, Flora Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bliss, Robin UNSPECIFIED UNSPECIFIED UNSPECIFIED Squires, Liza UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-796571
Identification Number:	10.1002/jimd.70000
Journal or Publication Title:	Journal of Inherited Metabolic Disease
Volume:	48
Number:	2
Page Range:	pp. 1-11
Date:	25 March 2025
Publisher:	Wiley
ISSN:	0141-8955
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences Faculty of Medicine
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry Zentrum für Molekulare Medizin
Subjects:	Chemistry and allied sciences Life sciences
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/79657