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

Orphanet J Rare Dis. 2021 Feb 27;16(1):107. doi: 10.1186/s13023-021-01739-y.

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.

Keywords: Acid sphingomyelinase deficiency; Apolipoprotein B100; Enzyme replacement therapy; Low density lipoprotein cholesterol; Proprotein convertase subtilisin/klexin type 9; Tumour necrosis factor α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apolipoprotein B-100 / metabolism*
  • Enzyme Replacement Therapy*
  • Humans
  • Niemann-Pick Disease, Type A*
  • Proprotein Convertase 9 / metabolism*
  • Recombinant Proteins / therapeutic use
  • Sphingomyelin Phosphodiesterase / therapeutic use*

Substances

  • Apolipoprotein B-100
  • Recombinant Proteins
  • Sphingomyelin Phosphodiesterase
  • olipudase alfa
  • PCSK9 protein, human
  • Proprotein Convertase 9