Scholarlink

Background <p>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 <i>N</i>-acetyl-<span>d</span>-mannosamine monohydrate (ManNAc), a precursor in the biosynthesis of <i>N</i>-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.</p> Objectives <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p> Clinical Trial Registration <p>The clinical trial was registered on the Australian New Zealand Clinical Trials Registry (ID: ACTRN12620001127998).</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Alternative Dosing Strategies to Enhance the Absorption of N-Acetyl-d-Mannosamine Monohydrate (ManNAc) in Healthy Adult Males

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月28日

查看全文
  • Tahlia R. Meola,
  • Kellie La Fontaine,
  • James Condon,
  • Paul Wabnitz,
  • Gianfranco Fornasini,
  • Allan M. Evans,
  • Stephanie E. Reuter

摘要

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).