Prospective exploratory muscle biopsy, imaging, and functional assessment in patients with late-onset Pompe disease treated with alglucosidase alfa: The EMBASSY Study

Ans van der Ploeg, Pierre G. Carlier, Robert Yves Carlier, John T. Kissel, Benedikt Schoser, Stephan Wenninger, Alan Pestronk, Richard J. Barohn, Mazen M. Dimachkie, Ozlem Goker-Alpan, Tahseen Mozaffar, Loren D.M. Pena, Zachary Simmons, Volker Straub, Michela Guglieri, Peter Young, Matthias Boentert, Pierre Yves Baudin, Stephan Wens, Raheel ShafiCarl Bjartmar, Beth L. Thurberg

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background Late-onset Pompe disease is characterized by progressive skeletal myopathy followed by respiratory muscle weakness, typically leading to loss of ambulation and respiratory failure. In this population, enzyme replacement therapy (ERT) with alglucosidase alfa has been shown to stabilize respiratory function and improve mobility and muscle strength. Muscle pathology and glycogen clearance from skeletal muscle in treatment-naïve adults after ERT have not been extensively examined. Methods This exploratory, open-label, multicenter study evaluated glycogen clearance in muscle tissue samples collected pre- and post- alglucosidase alfa treatment in treatment-naïve adults with late-onset Pompe disease. The primary endpoint was the quantitative reduction in percent tissue area occupied by glycogen in muscle biopsies from baseline to 6 months. Secondary endpoints included qualitative histologic assessment of tissue glycogen distribution, secondary pathology changes, assessment of magnetic resonance images (MRIs) for intact muscle and fatty replacement, and functional assessments. Results Sixteen patients completed the study. After 6 months of ERT, the percent tissue area occupied by glycogen in quadriceps and deltoid muscles decreased in 10 and 8 patients, respectively. No changes were detected on MRI from baseline to 6 months. A majority of patients showed improvements on functional assessments after 6 months of treatment. All treatment-related adverse events were mild or moderate. Conclusions This exploratory study provides novel insights into the histopathologic effects of ERT in late-onset Pompe disease patients. Ultrastructural examination of muscle biopsies demonstrated reduced lysosomal glycogen after ERT. Findings are consistent with stabilization of disease by ERT in treatment-naïve patients with late-onset Pompe disease.

Original languageEnglish (US)
Pages (from-to)115-123
Number of pages9
JournalMolecular Genetics and Metabolism
Volume119
Issue number1-2
DOIs
StatePublished - Sep 1 2016

Fingerprint

Functional assessment
Glycogen Storage Disease Type II
Enzyme Replacement Therapy
Biopsy
Glycogen
Muscle
Imaging techniques
Muscles
Enzymes
Tissue
Magnetic Resonance Spectroscopy
Therapeutics
Pathology
Deltoid Muscle
Magnetic resonance
Respiratory Muscles
Muscle Weakness
Quadriceps Muscle
Muscle Strength
Muscular Diseases

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

van der Ploeg, Ans ; Carlier, Pierre G. ; Carlier, Robert Yves ; Kissel, John T. ; Schoser, Benedikt ; Wenninger, Stephan ; Pestronk, Alan ; Barohn, Richard J. ; Dimachkie, Mazen M. ; Goker-Alpan, Ozlem ; Mozaffar, Tahseen ; Pena, Loren D.M. ; Simmons, Zachary ; Straub, Volker ; Guglieri, Michela ; Young, Peter ; Boentert, Matthias ; Baudin, Pierre Yves ; Wens, Stephan ; Shafi, Raheel ; Bjartmar, Carl ; Thurberg, Beth L. / Prospective exploratory muscle biopsy, imaging, and functional assessment in patients with late-onset Pompe disease treated with alglucosidase alfa : The EMBASSY Study. In: Molecular Genetics and Metabolism. 2016 ; Vol. 119, No. 1-2. pp. 115-123.
@article{0a422dfb004d49d4833f63f8471783ed,
title = "Prospective exploratory muscle biopsy, imaging, and functional assessment in patients with late-onset Pompe disease treated with alglucosidase alfa: The EMBASSY Study",
abstract = "Background Late-onset Pompe disease is characterized by progressive skeletal myopathy followed by respiratory muscle weakness, typically leading to loss of ambulation and respiratory failure. In this population, enzyme replacement therapy (ERT) with alglucosidase alfa has been shown to stabilize respiratory function and improve mobility and muscle strength. Muscle pathology and glycogen clearance from skeletal muscle in treatment-na{\"i}ve adults after ERT have not been extensively examined. Methods This exploratory, open-label, multicenter study evaluated glycogen clearance in muscle tissue samples collected pre- and post- alglucosidase alfa treatment in treatment-na{\"i}ve adults with late-onset Pompe disease. The primary endpoint was the quantitative reduction in percent tissue area occupied by glycogen in muscle biopsies from baseline to 6 months. Secondary endpoints included qualitative histologic assessment of tissue glycogen distribution, secondary pathology changes, assessment of magnetic resonance images (MRIs) for intact muscle and fatty replacement, and functional assessments. Results Sixteen patients completed the study. After 6 months of ERT, the percent tissue area occupied by glycogen in quadriceps and deltoid muscles decreased in 10 and 8 patients, respectively. No changes were detected on MRI from baseline to 6 months. A majority of patients showed improvements on functional assessments after 6 months of treatment. All treatment-related adverse events were mild or moderate. Conclusions This exploratory study provides novel insights into the histopathologic effects of ERT in late-onset Pompe disease patients. Ultrastructural examination of muscle biopsies demonstrated reduced lysosomal glycogen after ERT. Findings are consistent with stabilization of disease by ERT in treatment-na{\"i}ve patients with late-onset Pompe disease.",
author = "{van der Ploeg}, Ans and Carlier, {Pierre G.} and Carlier, {Robert Yves} and Kissel, {John T.} and Benedikt Schoser and Stephan Wenninger and Alan Pestronk and Barohn, {Richard J.} and Dimachkie, {Mazen M.} and Ozlem Goker-Alpan and Tahseen Mozaffar and Pena, {Loren D.M.} and Zachary Simmons and Volker Straub and Michela Guglieri and Peter Young and Matthias Boentert and Baudin, {Pierre Yves} and Stephan Wens and Raheel Shafi and Carl Bjartmar and Thurberg, {Beth L.}",
year = "2016",
month = "9",
day = "1",
doi = "10.1016/j.ymgme.2016.05.013",
language = "English (US)",
volume = "119",
pages = "115--123",
journal = "Molecular Genetics and Metabolism",
issn = "1096-7192",
publisher = "Academic Press Inc.",
number = "1-2",

}

van der Ploeg, A, Carlier, PG, Carlier, RY, Kissel, JT, Schoser, B, Wenninger, S, Pestronk, A, Barohn, RJ, Dimachkie, MM, Goker-Alpan, O, Mozaffar, T, Pena, LDM, Simmons, Z, Straub, V, Guglieri, M, Young, P, Boentert, M, Baudin, PY, Wens, S, Shafi, R, Bjartmar, C & Thurberg, BL 2016, 'Prospective exploratory muscle biopsy, imaging, and functional assessment in patients with late-onset Pompe disease treated with alglucosidase alfa: The EMBASSY Study', Molecular Genetics and Metabolism, vol. 119, no. 1-2, pp. 115-123. https://doi.org/10.1016/j.ymgme.2016.05.013

Prospective exploratory muscle biopsy, imaging, and functional assessment in patients with late-onset Pompe disease treated with alglucosidase alfa : The EMBASSY Study. / van der Ploeg, Ans; Carlier, Pierre G.; Carlier, Robert Yves; Kissel, John T.; Schoser, Benedikt; Wenninger, Stephan; Pestronk, Alan; Barohn, Richard J.; Dimachkie, Mazen M.; Goker-Alpan, Ozlem; Mozaffar, Tahseen; Pena, Loren D.M.; Simmons, Zachary; Straub, Volker; Guglieri, Michela; Young, Peter; Boentert, Matthias; Baudin, Pierre Yves; Wens, Stephan; Shafi, Raheel; Bjartmar, Carl; Thurberg, Beth L.

In: Molecular Genetics and Metabolism, Vol. 119, No. 1-2, 01.09.2016, p. 115-123.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Prospective exploratory muscle biopsy, imaging, and functional assessment in patients with late-onset Pompe disease treated with alglucosidase alfa

T2 - The EMBASSY Study

AU - van der Ploeg, Ans

AU - Carlier, Pierre G.

AU - Carlier, Robert Yves

AU - Kissel, John T.

AU - Schoser, Benedikt

AU - Wenninger, Stephan

AU - Pestronk, Alan

AU - Barohn, Richard J.

AU - Dimachkie, Mazen M.

AU - Goker-Alpan, Ozlem

AU - Mozaffar, Tahseen

AU - Pena, Loren D.M.

AU - Simmons, Zachary

AU - Straub, Volker

AU - Guglieri, Michela

AU - Young, Peter

AU - Boentert, Matthias

AU - Baudin, Pierre Yves

AU - Wens, Stephan

AU - Shafi, Raheel

AU - Bjartmar, Carl

AU - Thurberg, Beth L.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Background Late-onset Pompe disease is characterized by progressive skeletal myopathy followed by respiratory muscle weakness, typically leading to loss of ambulation and respiratory failure. In this population, enzyme replacement therapy (ERT) with alglucosidase alfa has been shown to stabilize respiratory function and improve mobility and muscle strength. Muscle pathology and glycogen clearance from skeletal muscle in treatment-naïve adults after ERT have not been extensively examined. Methods This exploratory, open-label, multicenter study evaluated glycogen clearance in muscle tissue samples collected pre- and post- alglucosidase alfa treatment in treatment-naïve adults with late-onset Pompe disease. The primary endpoint was the quantitative reduction in percent tissue area occupied by glycogen in muscle biopsies from baseline to 6 months. Secondary endpoints included qualitative histologic assessment of tissue glycogen distribution, secondary pathology changes, assessment of magnetic resonance images (MRIs) for intact muscle and fatty replacement, and functional assessments. Results Sixteen patients completed the study. After 6 months of ERT, the percent tissue area occupied by glycogen in quadriceps and deltoid muscles decreased in 10 and 8 patients, respectively. No changes were detected on MRI from baseline to 6 months. A majority of patients showed improvements on functional assessments after 6 months of treatment. All treatment-related adverse events were mild or moderate. Conclusions This exploratory study provides novel insights into the histopathologic effects of ERT in late-onset Pompe disease patients. Ultrastructural examination of muscle biopsies demonstrated reduced lysosomal glycogen after ERT. Findings are consistent with stabilization of disease by ERT in treatment-naïve patients with late-onset Pompe disease.

AB - Background Late-onset Pompe disease is characterized by progressive skeletal myopathy followed by respiratory muscle weakness, typically leading to loss of ambulation and respiratory failure. In this population, enzyme replacement therapy (ERT) with alglucosidase alfa has been shown to stabilize respiratory function and improve mobility and muscle strength. Muscle pathology and glycogen clearance from skeletal muscle in treatment-naïve adults after ERT have not been extensively examined. Methods This exploratory, open-label, multicenter study evaluated glycogen clearance in muscle tissue samples collected pre- and post- alglucosidase alfa treatment in treatment-naïve adults with late-onset Pompe disease. The primary endpoint was the quantitative reduction in percent tissue area occupied by glycogen in muscle biopsies from baseline to 6 months. Secondary endpoints included qualitative histologic assessment of tissue glycogen distribution, secondary pathology changes, assessment of magnetic resonance images (MRIs) for intact muscle and fatty replacement, and functional assessments. Results Sixteen patients completed the study. After 6 months of ERT, the percent tissue area occupied by glycogen in quadriceps and deltoid muscles decreased in 10 and 8 patients, respectively. No changes were detected on MRI from baseline to 6 months. A majority of patients showed improvements on functional assessments after 6 months of treatment. All treatment-related adverse events were mild or moderate. Conclusions This exploratory study provides novel insights into the histopathologic effects of ERT in late-onset Pompe disease patients. Ultrastructural examination of muscle biopsies demonstrated reduced lysosomal glycogen after ERT. Findings are consistent with stabilization of disease by ERT in treatment-naïve patients with late-onset Pompe disease.

UR - http://www.scopus.com/inward/record.url?scp=84990985825&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84990985825&partnerID=8YFLogxK

U2 - 10.1016/j.ymgme.2016.05.013

DO - 10.1016/j.ymgme.2016.05.013

M3 - Article

C2 - 27473031

AN - SCOPUS:84990985825

VL - 119

SP - 115

EP - 123

JO - Molecular Genetics and Metabolism

JF - Molecular Genetics and Metabolism

SN - 1096-7192

IS - 1-2

ER -