Enzyme Replacement Therapy With Elosulfase Alfa Decreases Storage of Glycosaminoglycan in White Blood Cells of Patients With Morquio A Syndrome

Guilherme Baldo,Rejane Gus,Fabiano Poswar,Roberto Giugliani,Camila Bittar,Andressa Federhen,Fernanda Bender

doi:10.1177/2326409814567741

Abstract

Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disorder caused by a deficient N-acetylgalactosamine-6-sulfate sulfatase activity, leading to cellular storage of undegraded keratan sulfate. Recently enzyme replacement therapy (ERT) was approved for MPS IVA, but some of ERT effects are still unknown. In the present study, we aimed to evaluate the efficacy of elosulfase alfa upon glycosaminoglycan (GAG) storage in peripheral blood white blood cells of patients with MPS IVA treated for 6 months, comparing samples from patients who received weekly infusions of enzyme (ERT-W) versus infusions every other week (ERT-EOW) versus placebo. A significant reduction in GAG storage was observed in both ERT-treated groups, with weekly ERT showing slightly better performance than ERT-EOW.

Highlights

Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disorder caused by deficient activity of N-acetylgalactosamine-6-sulfate sulfatase, leading to cellular storage of undegraded keratan sulfate (KS).[1]
The goal of the present work was to evaluate the effect of enzyme replacement therapy (ERT) upon GAG storage in peripheral blood white blood cells (WBCs) of patients with MPS IVA who participated in a phase III double-blind, placebo-controlled randomized clinical trial (Strive, sponsored by BioMarin Pharmaceutical), comparing samples from 3 different patient groups, that is, those who received weekly infusions of enzyme (ERT-W) versus patients who received infusions every other week (ERTEOW) versus patients enrolled in the placebo (PLA) group
Comparing PLA versus both treated groups together, ERT increased the number of cells without observed GAG storage (18.0% + 8.1% of cells with no storage observed in PLA vs 48.5% + 22.5% in ERT treated, P < .01)

Summary

Introduction

Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disorder caused by deficient activity of N-acetylgalactosamine-6-sulfate sulfatase, leading to cellular storage of undegraded keratan sulfate (KS).[1]. Patients with Morquio A syndrome typically present progressive bone and joint problems that lead to short stature and bone deformities.[3] glycosaminoglycan (GAG) storage occurs in multiple organs, including the lung, aorta, heart valves, heart muscle, visceral organs, and bone marrow.[4] An effective treatment of those alterations is very important, since these abnormalities can cause significant morbidity and even lead to death in these patients.[5] Based on that, the goal of the present work was to evaluate the effect of ERT upon GAG storage in peripheral blood white blood cells (WBCs) of patients with MPS IVA who participated in a phase III double-blind, placebo-controlled randomized clinical trial (Strive, sponsored by BioMarin Pharmaceutical), comparing samples from 3 different patient groups, that is, those who received weekly infusions of enzyme (ERT-W) versus patients who received infusions every other week (ERTEOW) versus patients enrolled in the placebo (PLA) group

Objectives

Methods

Results