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Background <p>Acid sphingomyelinase deficiency (ASMD) A and B, historically known as Niemann-Pick (NP) types A (NPA) and B (NPB), are life-threatening and rare inherited lysosomal storage disorders, caused by a deficiency in the acid sphingomyelinase enzyme activity. The negative outcome of this deficiency is the sphingomyelin (SM) accumulation in different organs and tissues. Trehalose is a natural disaccharide with neuroprotective and autophagy-inducing abilities that has recently been shown to improve clinical and biochemical features of patients with ASMD A/B. We previously showed that trehalose can reduce the serum levels of sphingomyelins and improve disease symptoms caused by lipid accumulation in ASMD A/B patients.</p> Aim <p>The aim of this study was to investigate the serum metabolome changes in five patients with ASMD A/B, who received 15&#xa0;g/week of trehalose intravenously for three months, using an untargeted gas chromatography-mass spectrometry (GC-MS) method.</p> Methods and materials <p>GC-MS technique was used to assess the serum metabolic profile of patients with ASMD A/B. MSDIAL was used for data processing, and multivariate data analysis including Principal Component Analysis (PCA), and Orthogonal projections to latent structures discriminant analysis (OPLS-DA) algorithms were carried out using SIMCA.</p> Results <p>OPLS-DA model revealed significant changes in several serum metabolites including phosphate (<i>P</i> = 0.0019), sorbitol (<i>P</i> = 0.00009), myoinositol (<i>P</i> = 0.02), threonine (<i>P</i> = 0.01), lactic acid (<i>P</i> = 0.0001), 1-monopalmitin (<i>P</i> = 0.01), threitol (<i>P</i> = 0.002), ribitol (<i>P</i> = 0.008), and D-ribose (<i>P</i> = 0.007) following trehalose treatment.</p> Conclusion <p>The findings revealed that the beneficial effects of trehalose in patients with ASMD might be mediated by metabolic alterations. A clear shift in glucose metabolism in favor of less fatty acid production together with facilitating the breakdown of sphingomyelins is involved in the observed protective activity.</p>

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Metabolic improvement in patients with acid sphingomyelinase deficiency following intravenous trehalose administration: an untargeted pharmacometabolomic study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月7日

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  • Mahdieh Khoshakhlagh,
  • Maede Hasanpour,
  • Mehrdad Iranshahi,
  • Javad Asili,
  • Aida Tasbandi,
  • Tannaz Jamialahmadi,
  • Amirhossein Sahebkar,
  • Milad Iranshahy

摘要

Background

Acid sphingomyelinase deficiency (ASMD) A and B, historically known as Niemann-Pick (NP) types A (NPA) and B (NPB), are life-threatening and rare inherited lysosomal storage disorders, caused by a deficiency in the acid sphingomyelinase enzyme activity. The negative outcome of this deficiency is the sphingomyelin (SM) accumulation in different organs and tissues. Trehalose is a natural disaccharide with neuroprotective and autophagy-inducing abilities that has recently been shown to improve clinical and biochemical features of patients with ASMD A/B. We previously showed that trehalose can reduce the serum levels of sphingomyelins and improve disease symptoms caused by lipid accumulation in ASMD A/B patients.

Aim

The aim of this study was to investigate the serum metabolome changes in five patients with ASMD A/B, who received 15 g/week of trehalose intravenously for three months, using an untargeted gas chromatography-mass spectrometry (GC-MS) method.

Methods and materials

GC-MS technique was used to assess the serum metabolic profile of patients with ASMD A/B. MSDIAL was used for data processing, and multivariate data analysis including Principal Component Analysis (PCA), and Orthogonal projections to latent structures discriminant analysis (OPLS-DA) algorithms were carried out using SIMCA.

Results

OPLS-DA model revealed significant changes in several serum metabolites including phosphate (P = 0.0019), sorbitol (P = 0.00009), myoinositol (P = 0.02), threonine (P = 0.01), lactic acid (P = 0.0001), 1-monopalmitin (P = 0.01), threitol (P = 0.002), ribitol (P = 0.008), and D-ribose (P = 0.007) following trehalose treatment.

Conclusion

The findings revealed that the beneficial effects of trehalose in patients with ASMD might be mediated by metabolic alterations. A clear shift in glucose metabolism in favor of less fatty acid production together with facilitating the breakdown of sphingomyelins is involved in the observed protective activity.