scholarly journals Changes in PCSK 9 and apolipoprotein B100 in Niemann–Pick disease after enzyme replacement therapy with olipudase alfa

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Bethanie Garside ◽  
Jan Hoong Ho ◽  
See Kwok ◽  
Yifen Liu ◽  
Shaishav Dhage ◽  
...  
Keyword(s):  
Reference Group ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Enzyme Replacement ◽  
Niemann Pick Disease ◽  
Tnf Α ◽  
Niemann Pick ◽  
Lipid Parameters

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.

scholarly journals Changes in PCSK 9 and Apolipoprotein B100 in Niemann-Pick Disease After Enzyme Replacement Therapy with Olipudase Alfa

2021 ◽  
Author(s):  
Bethanie Garside ◽  
Jan Hoong Ho ◽  
See Kwok ◽  
Yifen Liu ◽  
Shaishav Dhage ◽  
...  
Keyword(s):  
Reference Group ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Enzyme Replacement ◽  
Niemann Pick Disease ◽  
Tnf Α ◽  
Niemann Pick ◽  
Lipid Parameters

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.

scholarly journals Changes in PCSK 9 and Apolipoprotein B100 in Niemann-Pick Disease After Enzyme Replacement Therapy with Olipudase Alfa

2020 ◽  
Author(s):  
See Kwok ◽  
Bethanie Garside ◽  
Jan Hoong Ho ◽  
Yifen Liu ◽  
Shaishav Dhage ◽  
...  
Keyword(s):  
Reference Group ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Enzyme Replacement ◽  
Niemann Pick Disease ◽  
Tnf Α ◽  
Niemann Pick ◽  
Lipid Parameters

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.

Apolipoprotein B and non-high-density lipoprotein cholesterol reveal a high atherogenicity in individuals with type 2 diabetes and controlled low-density lipoprotein-cholesterol

2020 ◽  
Author(s):  
Liliana Fonseca ◽  
Sílvia Paredes ◽  
Helena Ramos ◽  
José Carlos Oliveira ◽  
Isabel Palma
Keyword(s):  
Type 2 Diabetes ◽  
Lipid Profile ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Lipid Parameters

Abstract Purpose: Lipid-lowering therapy is guided by Low-density-lipoprotein cholesterol (LDL-c), although the CVD risk could be better reflected by other lipid parameters. This study aimed the evaluation of a comprehensive lipid profile in patients with type 2 diabetes mellitus (T2DM) and comparation of those achieving and not achieving LDL-c control in respect to other non-conventional lipid parameters. Methods: We characterized a comprehensive lipid profile in 96 T2DM patients. ESC/EAS 2016 and 2019 Guidelines for the Management of Dyslipidemias were used to define LDL-c targets. Atherogenic lipoprotein profile was compared in patients with LDL-c within and above the target. Results: Only 28.1% and 16.7% of patients had mean LDL-c levels within the 2016 and 2019 guidelines, respectively. In patients with LDL-c within target by the 2016 guidelines, 22%, 25% and 44% presented levels above the recommended range for non-HDL-c, ApoB and oxidized LDL-c, respectively, whereas accordingly to the 2019 guidelines, 50%, 39% and 44% had elevated levels of -HDL-c, ApoB and oxidized LDL-c, respectively. There was a significant strong association of LDL-c and non-HDL-c (r=0.850), ApoB (r=0.656) and oxidized LDL-c (r=0.508). Similarly, non-HDL-c was significantly strongly correlated with ApoB (r=0.808) and oxidized LDL-c (r=0.588). Conclusions: These findings emphasize the limitations of a sole LDL-c measurement for CV risk assessment. Targeting only LDL-c could result in missed opportunities for CV risk reduction in T2DM individuals. Our data suggest that non-HDL-c, ApoB and oxidized LDL-c could be considered as part of these patients’ evaluation allowing a more accurate estimation of CV risk and treatment among these high-risk patients.

scholarly journals The Effect of Daily Walnut Consumption on Dyslipidemia

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
İbrahim Bashan ◽  
Mustafa Bakman
Keyword(s):  
High Density Lipoprotein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
Lipoprotein Cholesterol ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Cholesterol Levels ◽  
Lipid Parameters

The aim of this study was to investigate the effect of daily walnut consumption on dyslipidemia in dietary. Within a year, the patients who have been suggested taking walnut or not in their individual dietary were scanned retrospectively and randomized into 2 groups. The first group consists of 72 cases (only those taken on the diet program) and the second group consists of 73 cases (walnut consumption in regulated diet). Baseline blood lipid parameters and anthropometric measurements were assessed in both groups and compared with values at 3rd month. p values < 0.05 were considered statistically significant. In addition, Maras 18 walnut cultivar was analyzed to determine the fatty acid profiles by chromatographic technique. When comparing lipid parameters at baseline and at the 3rd month, total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and triglyceride levels significantly decreased and high-density lipoprotein cholesterol levels significantly increased. As compared with the end of 3rd month values of the groups, the reduction in total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, triglyceride levels of the subjects group (walnut consumption in regulated diet) were significantly higher than the control group (only regulated diet). Also, there was no significant difference in increase on high-density lipoprotein cholesterol levels between the groups. The results showed that daily consumption of walnut improved blood lipid levels. However, more extensive studies are needed on therapeutic usage in dyslipidemia.

Sign in / Sign up

Export Citation Format

Share Document