See the published version of this preprint at Orphanet Journal of Rare Diseases.
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Handrean Soran
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1714-5014
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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.
Keywords
Acid Sphingomyelinase Deficiency, apolipoprotein B100, proprotein convertase subtilisin/klexin type 9, tumour necrosis factor α, low density lipoprotein cholesterol, enzyme replacement therapy
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CURRENT STATUS: Published
View the published article at Orphanet Journal of Rare Diseases.
Version 2
Posted 15 Jan, 2021
No community comments so far
Editorial decision: Accept
On 06 Feb, 2021
Reviewer #2 agreed
On 31 Jan, 2021
Review #2 received
Received 31 Jan, 2021
Reviewer #1 agreed
On 28 Jan, 2021
Review #1 received
Received 28 Jan, 2021
Reviewers invited
Invitations sent on 19 Jan, 2021
Editor assigned
On 07 Jan, 2021
Submission checks complete
On 07 Jan, 2021
Editor invited
On 07 Jan, 2021
No comments provided
Review #2 received
Received 17 Nov, 2020
Editorial decision: Major revision
On 17 Nov, 2020
Reviewer #2 agreed
On 03 Nov, 2020
Review #1 received
Received 20 Oct, 2020
Reviewers invited
Invitations sent on 19 Oct, 2020
Reviewer #1 agreed
On 19 Oct, 2020
Editor assigned
On 17 Aug, 2020
First submitted
On 16 Aug, 2020
Submission checks complete
On 16 Aug, 2020
Editor invited
On 16 Aug, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Internal Medicine
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See the published version of this preprint at Orphanet Journal of Rare Diseases.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Handrean Soran
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1714-5014
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Orphanet Journal of Rare Diseases.
Version 2
Posted 15 Jan, 2021
No community comments so far
Editorial decision: Accept
On 06 Feb, 2021
Reviewer #2 agreed
On 31 Jan, 2021
Review #2 received
Received 31 Jan, 2021
Reviewer #1 agreed
On 28 Jan, 2021
Review #1 received
Received 28 Jan, 2021
Reviewers invited
Invitations sent on 19 Jan, 2021
Editor assigned
On 07 Jan, 2021
Submission checks complete
On 07 Jan, 2021
Editor invited
On 07 Jan, 2021
No comments provided
Review #2 received
Received 17 Nov, 2020
Editorial decision: Major revision
On 17 Nov, 2020
Reviewer #2 agreed
On 03 Nov, 2020
Review #1 received
Received 20 Oct, 2020
Reviewers invited
Invitations sent on 19 Oct, 2020
Reviewer #1 agreed
On 19 Oct, 2020
Editor assigned
On 17 Aug, 2020
First submitted
On 16 Aug, 2020
Submission checks complete
On 16 Aug, 2020
Editor invited
On 16 Aug, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Internal Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Orphanet Journal of Rare Diseases.
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.
Figure 1
Figure 2
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