N-Acetylneuraminic Acid Storage Disease Clinical Trial
Official title:
Sialic Acid Supplementation in NANS Deficiency: An Open-label, Proof of Concept, Two-centers Study
This study is aimed at assessing the impact of short-term (3 days) exogenous sialic acid supplementation on endogenous biomarkers of sialic acid metabolism in NANS deficient patients.
NANS deficiency is a genetic disorder presenting clinically with intellectual development
disorder, skeletal dysplasia and dysmorphic features. It has recently been described in 9
patients (4 children and 5 adults). Biallelic mutations in the NANS (N-Acetylneuraminic acid
synthase) gene cause a block in the endogenous synthesis of sialic acid and accumulation of
the precursor, N-acetyl mannosamine (ManNAc). In a cell culture model, this block results in
hyposialylation of glycoproteins and glycolipids. It seems likely that in human, this enzyme
deficiency impairs the sialylation of glycolipids and glycoproteins, known to be essential
for brain development. Exogenously added sialic acid partially rescued the phenotype of
NANS-deficient zebra fish. Currently there is no approved treatment for patients with NANS
deficiency. The investigators concluded that exogenous sialic acid supplementation might be
useful for NANS patients. Given that sialic acid is found as both, a free sugar and in a
bound form in standard nutrition as well as in high quantities in breast milk, it can be
considered as a safe nutritional ingredient; this notion is fully supported by animal
toxicity studies.
The use of sialic acid in NANS deficiency is in line with oral supplementation of specific
sugars for treatment of other glycosylation and sialylation defects such as congenital
disorders of glycosylation (CDG) and myopathy with mutation in the gene GNE. This novel
monosaccharide therapy represents an opportunity to address fundamental biochemical questions
about the relative contribution of endogenous and dietary sources on sialic acid metabolism
and its potential role as a future therapy for NANS patients.
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