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.

PMID: 33639994

Bethanie Garside, Jan Hoong Ho, See Kwok

Highlights: In this study, in which Niemann pick patients were included, it was aimed to assess the effect of enzyme replacement therapy (ERT) on lipid parameters and inflammatory markers.

Abstract

Background: For the treatment of individuals with ASM deficiency (ASMD), also known as Niemann-Pick disease (NPD) types A or B, olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is being developed. The purpose of this study was to evaluate how ERT affected lipid parameters and inflammatory markers.

Methods: Five adults with NPD type B (NPD-B) who received olipudase alfa ERT for 26 weeks had serum and plasma samples analyzed. As a reference and comparison group, fasting blood samples are also obtained from fifteen participants who were matched for age and sex. The oxidized low-density lipoprotein (oxLDL), small dense low-density lipoprotein cholesterol (sdLDL-C), apolipoproteins B48 and B100 (apoB48 and apoB100), apolipoprotein A1 (apoA1), proprotein convertase subtilisin/klexin type 9 (PCSK9) mass, and tumor necrosis factor α (TNF-α) were all measured.

Results: Patients with NPD-B showed lower levels of high density lipoprotein cholesterol (HDL-C) and apoA1, and greater levels of triglycerides, PCSK9, apoB48, oxLDL, and TNF-α than the age- and sex-matched reference group. Improvements in lipid markers, such as total cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C), sdLDL-C, oxLDL, and apoB100, were linked to ERT treatment. HDL-C was marginally decreased even though apoA1 was up. TNF-α exhibited a decrease. Following ERT, the overall serum PCSK9 mass dropped concurrently with a decrease in apoB100.

Conclusion: According to this study, patients with NPD-B showed proatherogenic lipid profiles and greater levels of circulating TNF-α than the control group. After taking olipudase alfa, dyslipidemia improved. It was probable that decreases in TNF-α and PCSK9 following ERT were what caused decreases in LDL-C and apoB100.

Keywords: Acid sphingomyelinase deficiency, Apolipoprotein B100, Enzyme replacement therapy, LDL cholesterol, PCSK9, TNF-α