Alternative Dosing Strategies to Enhance the Absorption of N-Acetyl-D-Mannosamine Monohydrate (ManNAc) in Healthy Adult Males
Date
2026
Authors
Meola, T.R.
La Fontaine, K.
Condon, J.
Wabnitz, P.
Fornasini, G.
Evans, A.M.
Reuter, S.E.
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Advisors
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Journal article
Citation
Clinical Drug Investigation, 2026; 46(5):1-10
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Tahlia R. Meola, Kellie La Fontaine, James Condon, Paul Wabnitz, Gianfranco Fornasini, Allan M. Evans, Stephanie E. Reuter
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Abstract
Background: GNE myopathy is a rare autosomal recessive muscle disease caused by biallelic mutations in GNE, a gene which encodes the bifunctional enzyme that catalyses the rate-limiting step of intracellular sialic acid biosynthesis. Whilst there is no current marketed therapy to treat the disease, current investigations focus on supplementation with N-acetyl-d-mannosamine monohydrate (ManNAc), a precursor in the biosynthesis of N-acetylneuraminic acid (Neu5Ac), the most abundant sialic acid. ManNAc possesses a low oral bioavailability, likely owing to poor absorption, and exhibits non-linearity across the therapeutic range, possibly due to saturation of intestinal transporter systems. Objectives: The study was conducted to examine if the absorption of ManNAc could be improved by administering a smaller (non-saturating) oral dose, more frequently, or by co-administering ManNAc with dietary salt, which might facilitate carrier-mediated transport. Methods: This was an open-label, randomised, cross-over study in 12 healthy male participants. Participants were administered 4 x 1 g doses of ManNAc every hour, 4 g ManNAc as a single dose with 1 g dietary salt or 4 g ManNAc alone. Results: The pharmacokinetic analysis population comprised 11 participants who received all three study treatments. Administration of ManNAc as split doses, more frequently, resulted in a 1.7-fold increase in ManNAc plasma exposure compared to a single 4 g dose, with a corresponding 1.9-fold increase in systemic Neu5Ac concentrations. In comparison, co-administration of ManNAc with dietary salt had no impact on ManNAc absorption. Conclusions: This study suggests that strategies to slow down the delivery of ManNAc to the small intestine may significantly improve its overall bioavailability and therefore reduce total daily dose requirements. Clinical Trial Registration: The clinical trial was registered on the Australian New Zealand Clinical Trials Registry (ID: ACTRN12620001127998).
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© The Author(s) 2026. This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.