Apolipoprotein-mimetic nanodiscs reduce lipid accumulation and improve liver function in acid sphingomyelinase deficiency
Copyright © 2023. Published by Elsevier Inc..
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.
| Media Type: |
Electronic Article |
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| Year of Publication: |
2023 |
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| Publication: |
2023 |
| Contained In: |
To Main Record - volume:53 |
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| Contained In: |
Nanomedicine : nanotechnology, biology, and medicine - 53(2023) vom: 24. Aug., Seite 102705 |
| Language: |
English |
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| Contributors: |
Halseth, Troy A [Author] |
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| Links: |
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| Keywords: |
Acid sphingomyelinase deficiency |
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| Notes: |
Date Revised 03.09.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.nano.2023.102705 |
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| funding: |
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| Supporting institution / Project title: |
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| PPN (Catalogue-ID): |
NLM361397267 |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Acid sphingomyelinase deficiency | |
| 650 | 4 | |a Apolipoprotein mimetics | |
| 700 | 1 | |a Correia, Adele B |e verfasserin |4 aut | |
| 700 | 1 | |a Schultz, Mark L |e verfasserin |4 aut | |
| 700 | 1 | |a Fawaz, Maria V |e verfasserin |4 aut | |
| 700 | 1 | |a Kuiper, Esmée Q |e verfasserin |4 aut | |
| 700 | 1 | |a Kumaran, Preethi |e verfasserin |4 aut | |
| 700 | 1 | |a Dorsey, Kristen Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Schuchman, Edward H |e verfasserin |4 aut | |
| 700 | 1 | |a Lieberman, Andrew P |e verfasserin |4 aut | |
| 700 | 1 | |a Schwendeman, Anna |e verfasserin |4 aut | |
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