AI Article Synopsis
- Acid sphingomyelinase deficiency (ASMD) is a serious lipid storage disorder caused by low activity of the enzyme responsible for breaking down sphingomyelin, leading to neurological issues and organ enlargement.
- Researchers explored the potential of synthetic apolipoprotein A-I (ApoA-I) mimetics to act as lipid scavengers to treat ASMD, focusing on a lead peptide called 22A.
- The study found that 22A could effectively reduce sphingomyelin buildup in patient cells and, when administered as a synthetic high-density lipoprotein (sHDL) nanodisc in mice, improved liver function by mobilizing sphingomyelin into the bloodstream.
Article Abstract
Acid sphingomyelinase deficiency (ASMD) is a severe lipid storage disorder caused by the diminished activity of the acid sphingomyelinase enzyme. ASMD is characterized by the accumulation of sphingomyelin in late endosomes and lysosomes leading to progressive neurological dysfunction and hepatosplenomegaly. Our objective was to investigate the utility of synthetic apolipoprotein A-I (ApoA-I) mimetics designed to act as lipid scavengers for the treatment of ASMD. We determined the lead peptide, 22A, could reduce sphingomyelin accumulation in ASMD patient skin fibroblasts in a dose dependent manner. Intraperitoneal administration of 22A formulated as a synthetic high-density lipoprotein (sHDL) nanodisc mobilized sphingomyelin from peripheral tissues into circulation and improved liver function in a mouse model of ASMD. Together, our data demonstrates that apolipoprotein mimetics could serve as a novel therapeutic strategy for modulating the pathology observed in ASMD.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530155 | PMC |
| http://dx.doi.org/10.1016/j.nano.2023.102705 | DOI Listing |
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