Skip to main content
release_alert
Welcome to the new Scholars 3.0! Read about new features and let us know what you think.
cancel
Journal cover image

Outside the fiber: Endomysial stromal and capillary pathology in skeletal muscle may impede infusion therapy in infantile-onset Pompe disease.

Publication ,  Journal Article
Buckley, AF; Desai, AK; Ha, CI; Petersen, MA; Estrada, JC; Waterfield, JR; Bossen, EH; Kishnani, PS
Published in: J Neuropathol Exp Neurol
March 20, 2023

The survival of infantile-onset Pompe disease (IOPD) patients has improved dramatically since the introduction of enzyme replacement therapy (ERT) with a1glucosidase alfa. However, long-term IOPD survivors on ERT demonstrate motor deficits indicating that current therapy cannot completely prevent disease progression in skeletal muscle. We hypothesized that in IOPD, skeletal muscle endomysial stroma and capillaries would show consistent changes that could impede the movement of infused ERT from blood to muscle fibers. We retrospectively examined 9 skeletal muscle biopsies from 6 treated IOPD patients using light and electron microscopy. We found consistent ultrastructural endomysial stromal and capillary changes. The endomysial interstitium was expanded by lysosomal material, glycosomes/glycogen, cellular debris, and organelles, some exocytosed by viable muscle fibers and some released on fiber lysis. Endomysial scavenger cells phagocytosed this material. Mature fibrillary collagen was seen in the endomysium, and both muscle fibers and endomysial capillaries showed basal laminar reduplication and/or expansion. Capillary endothelial cells showed hypertrophy and degeneration, with narrowing of the vascular lumen. Ultrastructurally defined stromal and vascular changes likely constitute obstacles to movement of infused ERT from capillary lumen to muscle fiber sarcolemma, contributing to the incomplete efficacy of infused ERT in skeletal muscle. Our observations can inform approaches to overcoming these barriers to therapy.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Neuropathol Exp Neurol

DOI

EISSN

1554-6578

Publication Date

March 20, 2023

Volume

82

Issue

4

Start / End Page

345 / 362

Location

England

Related Subject Headings

  • alpha-Glucosidases
  • Retrospective Studies
  • Neurology & Neurosurgery
  • Muscle, Skeletal
  • Humans
  • Glycogen Storage Disease Type II
  • Endothelial Cells
  • Capillaries
  • Antibodies
  • 1109 Neurosciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Buckley, A. F., Desai, A. K., Ha, C. I., Petersen, M. A., Estrada, J. C., Waterfield, J. R., … Kishnani, P. S. (2023). Outside the fiber: Endomysial stromal and capillary pathology in skeletal muscle may impede infusion therapy in infantile-onset Pompe disease. J Neuropathol Exp Neurol, 82(4), 345–362. https://doi.org/10.1093/jnen/nlad012
Buckley, Anne F., Ankit K. Desai, Christine I. Ha, Maureen A. Petersen, Januario C. Estrada, Justin R. Waterfield, Edward H. Bossen, and Priya S. Kishnani. “Outside the fiber: Endomysial stromal and capillary pathology in skeletal muscle may impede infusion therapy in infantile-onset Pompe disease.J Neuropathol Exp Neurol 82, no. 4 (March 20, 2023): 345–62. https://doi.org/10.1093/jnen/nlad012.
Buckley AF, Desai AK, Ha CI, Petersen MA, Estrada JC, Waterfield JR, et al. Outside the fiber: Endomysial stromal and capillary pathology in skeletal muscle may impede infusion therapy in infantile-onset Pompe disease. J Neuropathol Exp Neurol. 2023 Mar 20;82(4):345–62.
Buckley, Anne F., et al. “Outside the fiber: Endomysial stromal and capillary pathology in skeletal muscle may impede infusion therapy in infantile-onset Pompe disease.J Neuropathol Exp Neurol, vol. 82, no. 4, Mar. 2023, pp. 345–62. Pubmed, doi:10.1093/jnen/nlad012.
Buckley AF, Desai AK, Ha CI, Petersen MA, Estrada JC, Waterfield JR, Bossen EH, Kishnani PS. Outside the fiber: Endomysial stromal and capillary pathology in skeletal muscle may impede infusion therapy in infantile-onset Pompe disease. J Neuropathol Exp Neurol. 2023 Mar 20;82(4):345–362.
Journal cover image

Published In

J Neuropathol Exp Neurol

DOI

EISSN

1554-6578

Publication Date

March 20, 2023

Volume

82

Issue

4

Start / End Page

345 / 362

Location

England

Related Subject Headings

  • alpha-Glucosidases
  • Retrospective Studies
  • Neurology & Neurosurgery
  • Muscle, Skeletal
  • Humans
  • Glycogen Storage Disease Type II
  • Endothelial Cells
  • Capillaries
  • Antibodies
  • 1109 Neurosciences