Changes in PCSK 9 and Apolipoprotein B100 in Niemann-Pick Disease After Enzyme Replacement Therapy with Olipudase Alfa
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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Posted 15 Jan, 2021
On 31 Jan, 2021
Received 31 Jan, 2021
On 28 Jan, 2021
Received 28 Jan, 2021
Invitations sent on 19 Jan, 2021
On 07 Jan, 2021
On 07 Jan, 2021
On 07 Jan, 2021
Received 17 Nov, 2020
On 17 Nov, 2020
On 03 Nov, 2020
Received 20 Oct, 2020
Invitations sent on 19 Oct, 2020
On 19 Oct, 2020
On 17 Aug, 2020
On 16 Aug, 2020
On 16 Aug, 2020
On 16 Aug, 2020
Changes in PCSK 9 and Apolipoprotein B100 in Niemann-Pick Disease After Enzyme Replacement Therapy with Olipudase Alfa
Posted 15 Jan, 2021
On 31 Jan, 2021
Received 31 Jan, 2021
On 28 Jan, 2021
Received 28 Jan, 2021
Invitations sent on 19 Jan, 2021
On 07 Jan, 2021
On 07 Jan, 2021
On 07 Jan, 2021
Received 17 Nov, 2020
On 17 Nov, 2020
On 03 Nov, 2020
Received 20 Oct, 2020
Invitations sent on 19 Oct, 2020
On 19 Oct, 2020
On 17 Aug, 2020
On 16 Aug, 2020
On 16 Aug, 2020
On 16 Aug, 2020
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