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Changes in PCSK 9 and apolipoprotein B100 in Niemann-Pick disease after enzyme replacement therapy with olipudase alfa.
Orphanet J Rare Dis. 2021 02 27; 16(1):107.OJ

Abstract

BACKGROUND

Enzyme replacement therapy (ERT) with olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is being developed to treat patients with ASM deficiency (ASMD), commonly known as Niemann-Pick disease (NPD) types A or B. This study assessed the effect of ERT on lipid parameters and inflammatory markers.

METHODS

Serum and plasma samples from five adults with NPD type B (NPD-B) who received olipudase alfa ERT for 26 weeks were analysed. We also collected fasting blood samples from fifteen age- and sex-matched participants as reference and comparison group. We measured fasting lipid profile, apolipoproteins B48 and B100 (apoB48 and apoB100), apolipoprotein A1 (apoA1), proprotein convertase subtilisin/klexin type 9 (PCSK9) mass, oxidised low-density lipoprotein (oxLDL), small dense low-density lipoprotein cholesterol (sdLDL-C) and tumour necrosis factor α (TNF-α).

RESULTS

Patients with NPD-B, compared with age and sex matched reference group, had higher triglycerides, PCSK9, apoB48, oxLDL and TNF-α and lower high density lipoprotein cholesterol (HDL-C) and apoA1. Treatment with ERT was associated with improved lipid parameters including total cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C), sdLDL-C, oxLDL and apoB100. Though there was an increase in apoA1, HDL-C was slightly reduced. TNF-α showed a reduction. ApoB100 decreased in parallel with a decrease in total serum PCSK9 mass after ERT.

CONCLUSION

This study demonstrated that patients with NPD-B had a proatherogenic lipid profile and higher circulating TNF-α compared to reference group. There was an improvement in dyslipidaemia after olipudase alfa. It was possible that reductions in LDL-C and apoB100 were driven by reductions in TNF-α and PCSK9 following ERT.

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Authors+Show Affiliations

Garside B
Lipid Research Group, Division of Cardiovascular Sciences, University of Manchester, Manchester, UK.
Ho JH
Lipid Research Group, Division of Cardiovascular Sciences, University of Manchester, Manchester, UK. Cardiovascular Trials Unit, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, UK.
Kwok S
Lipid Research Group, Division of Cardiovascular Sciences, University of Manchester, Manchester, UK.
Liu Y
Lipid Research Group, Division of Cardiovascular Sciences, University of Manchester, Manchester, UK.
Dhage S
Cardiovascular Trials Unit, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, UK.
Donn R
Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Iqbal Z
Lipid Research Group, Division of Cardiovascular Sciences, University of Manchester, Manchester, UK. Cardiovascular Trials Unit, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, UK.
Jones SA
Manchester Centre for Genomic Medicine, St Marys Hospital, Manchester University NHS Foundation Trust, Manchester, UK.
Soran H
Lipid Research Group, Division of Cardiovascular Sciences, University of Manchester, Manchester, UK. Handrean.Soran@mft.nhs.uk. Cardiovascular Trials Unit, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, UK. Handrean.Soran@mft.nhs.uk.

MeSH

AdultApolipoprotein B-100Enzyme Replacement TherapyHumansNiemann-Pick Disease, Type AProprotein Convertase 9Recombinant ProteinsSphingomyelin Phosphodiesterase

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33639994

Citation

Garside, Bethanie, et al. "Changes in PCSK 9 and Apolipoprotein B100 in Niemann-Pick Disease After Enzyme Replacement Therapy With Olipudase Alfa." Orphanet Journal of Rare Diseases, vol. 16, no. 1, 2021, p. 107.
Garside B, Ho JH, Kwok S, et al. Changes in PCSK 9 and apolipoprotein B100 in Niemann-Pick disease after enzyme replacement therapy with olipudase alfa. Orphanet J Rare Dis. 2021;16(1):107.
Garside, B., Ho, J. H., Kwok, S., Liu, Y., Dhage, S., Donn, R., Iqbal, Z., Jones, S. A., & Soran, H. (2021). Changes in PCSK 9 and apolipoprotein B100 in Niemann-Pick disease after enzyme replacement therapy with olipudase alfa. Orphanet Journal of Rare Diseases, 16(1), 107. https://doi.org/10.1186/s13023-021-01739-y
Garside B, et al. Changes in PCSK 9 and Apolipoprotein B100 in Niemann-Pick Disease After Enzyme Replacement Therapy With Olipudase Alfa. Orphanet J Rare Dis. 2021 02 27;16(1):107. PubMed PMID: 33639994.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Changes in PCSK 9 and apolipoprotein B100 in Niemann-Pick disease after enzyme replacement therapy with olipudase alfa. AU - Garside,Bethanie, AU - Ho,Jan Hoong, AU - Kwok,See, AU - Liu,Yifen, AU - Dhage,Shaishav, AU - Donn,Rachelle, AU - Iqbal,Zohaib, AU - Jones,Simon A, AU - Soran,Handrean, Y1 - 2021/02/27/ PY - 2020/08/16/received PY - 2021/02/11/accepted PY - 2021/2/28/entrez PY - 2021/3/1/pubmed PY - 2021/6/22/medline KW - Acid sphingomyelinase deficiency KW - Apolipoprotein B100 KW - Enzyme replacement therapy KW - Low density lipoprotein cholesterol KW - Proprotein convertase subtilisin/klexin type 9 KW - Tumour necrosis factor α SP - 107 EP - 107 JF - Orphanet journal of rare diseases JO - Orphanet J Rare Dis VL - 16 IS - 1 N2 - BACKGROUND: Enzyme replacement therapy (ERT) with olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is being developed to treat patients with ASM deficiency (ASMD), commonly known as Niemann-Pick disease (NPD) types A or B. This study assessed the effect of ERT on lipid parameters and inflammatory markers. METHODS: Serum and plasma samples from five adults with NPD type B (NPD-B) who received olipudase alfa ERT for 26 weeks were analysed. We also collected fasting blood samples from fifteen age- and sex-matched participants as reference and comparison group. We measured fasting lipid profile, apolipoproteins B48 and B100 (apoB48 and apoB100), apolipoprotein A1 (apoA1), proprotein convertase subtilisin/klexin type 9 (PCSK9) mass, oxidised low-density lipoprotein (oxLDL), small dense low-density lipoprotein cholesterol (sdLDL-C) and tumour necrosis factor α (TNF-α). RESULTS: Patients with NPD-B, compared with age and sex matched reference group, had higher triglycerides, PCSK9, apoB48, oxLDL and TNF-α and lower high density lipoprotein cholesterol (HDL-C) and apoA1. Treatment with ERT was associated with improved lipid parameters including total cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C), sdLDL-C, oxLDL and apoB100. Though there was an increase in apoA1, HDL-C was slightly reduced. TNF-α showed a reduction. ApoB100 decreased in parallel with a decrease in total serum PCSK9 mass after ERT. CONCLUSION: This study demonstrated that patients with NPD-B had a proatherogenic lipid profile and higher circulating TNF-α compared to reference group. There was an improvement in dyslipidaemia after olipudase alfa. It was possible that reductions in LDL-C and apoB100 were driven by reductions in TNF-α and PCSK9 following ERT. SN - 1750-1172 UR - https://www.unboundmedicine.com/medline/citation/33639994/Changes_in_PCSK_9_and_apolipoprotein_B100_in_Niemann_Pick_disease_after_enzyme_replacement_therapy_with_olipudase_alfa_ DB - PRIME DP - Unbound Medicine ER -