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. 2025 Mar;48(2):e70000.
doi: 10.1002/jimd.70000.

Increased Survival in Patients With Molybdenum Cofactor Deficiency Type A Treated With Cyclic Pyranopterin Monophosphate

Guenter Schwarz  1 , Donald G Basel  2 , Bernd C Schwahn  3 , Ronen Spiegel  4 , Flora Y Wong  5 , Robin Bliss  6 , Liza Squires  7
Affiliations

Increased Survival in Patients With Molybdenum Cofactor Deficiency Type A Treated With Cyclic Pyranopterin Monophosphate

Guenter Schwarz et al. J Inherit Metab Dis. 2025 Mar.

Abstract

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.

Keywords: MoCD Type A; cPMP; cyclic pyranopterin monophosphate; fosdenopterin; molybdenum cofactor deficiency.

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Conflict of interest statement

Guenter Schwarz reports conflicts for a member of the advisory board or similar committee with Origin Biosciences, consulting or speaker fee from Sentynl Therapeutics Inc., holding a patent with Sentynl Therapeutics Inc. and founder and CEO of Colbourne Pharmaceuticals GmbH involved in the early stages of development of cPMP therapy. Bernd C. Schwahn reports conflict for an honorarium for the advisory board from Bridge Bio Inc. and an educational grant from Origin Biosciences Inc. Liza Squires reports conflict for consulting or speaker fees from Sentynl Therapeutics Inc. and was employed by Bridge Bio Inc. Donald G. Basel, Ronen Spiegel, Flora Y. Wong, and Robin Bliss have no conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Studies used in comparison of cyclic pyranopterin monophosphate‐treated versus untreated patients with MoCD Type A. (A) Details of treatment studies (MCD‐501, MCD‐201, and MCD‐202) and untreated control study (MCD‐502); and (B) flow chart of treated patients pooled for the full analysis set.
FIGURE 2
FIGURE 2
Improvement in survival in patients with MoCD Type A treated with cPMP (FAS, full analysis set).
FIGURE 3
FIGURE 3
Improvement in cognitive and motor functioning with cPMP treatment. (A) Age‐equivalent scores in months from the Bayley cognitive subtest (prospective FAS); (B) Age‐equivalent scores in months from the Bayley fine motor subtest (prospective FAS); and (C) Age‐equivalent scores in months from the Bayley and gross motor subtest (prospective FAS).
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References

    1. Atwal P. S. and Scaglia F., “Molybdenum Cofactor Deficiency,” Molecular Genetics and Metabolism 117, no. 1 (2016): 1–4. - PubMed
    1. Johannes L., Fu C. Y., and Schwarz G., “Molybdenum Cofactor Deficiency in Humans,” Molecules 27, no. 20 (2022): 6896. - PMC - PubMed
    1. Mechler K., Mountford W. K., Hoffmann G. F., and Ries M., “Ultra‐Orphan Diseases: A Quantitative Analysis of the Natural History of Molybdenum Cofactor Deficiency,” Genetics in Medicine 17, no. 12 (2015): 965–970. - PubMed
    1. Kumar A., Dejanovic B., Hetsch F., et al., “S‐Sulfocysteine/NMDA Receptor‐Dependent Signaling Underlies Neurodegeneration in Molybdenum Cofactor Deficiency,” Journal of Clinical Investigation 127, no. 12 (2017): 4365–4378. - PMC - PubMed
    1. Misko A., Mahtani K., Abbott J., Schwarz G., and Atwal P., GeneReviews®, eds. Adam M. P., Feldman J., Mirzaa G. M., Pagon R. A., Wallace S. E., and A. Amemiya (Seattle, Washington DC: University of Washington, 1993). - PubMed

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