Antibody-Mediated Enzyme Therapeutics and Applications in Glycogen Storage Diseases

Zhengqiu Zhou; Grant L. Austin; Robert Shaffer; Dustin D. Armstrong; Matthew S. Gentry

doi:10.1016/j.molmed.2019.08.005

Antibody-Mediated Enzyme Therapeutics and Applications in Glycogen Storage Diseases

Zhengqiu Zhou
, Grant L. Austin
, Robert Shaffer
, Dustin D. Armstrong
, Matthew S. Gentry

Research output: Contribution to journal › Review article › peer-review

36 Scopus citations

Abstract

The use of antibodies as targeting molecules or cell-penetrating tools has emerged at the forefront of pharmaceutical research. Antibody-directed therapies in the form of antibody–drug conjugates, immune modulators, and antibody-directed enzyme prodrugs have been most extensively utilized as hematological, rheumatological, and oncological therapies, but recent developments are identifying additional applications of antibody-mediated delivery systems. A novel application of this technology is for the treatment of glycogen storage disorders (GSDs) via an antibody–enzyme fusion (AEF) platform to penetrate cells and deliver an enzyme to the cytoplasm, nucleus, and/or other organelles. Exciting developments are currently underway for AEFs in the treatment of the GSDs Pompe disease and Lafora disease (LD). Antibody-based therapies are quickly becoming an integral part of modern disease therapeutics.

Original language	English
Pages (from-to)	1094-1109
Number of pages	16
Journal	Trends in Molecular Medicine
Volume	25
Issue number	12
DOIs	https://doi.org/10.1016/j.molmed.2019.08.005
State	Published - Dec 2019

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Ltd

Funding

We thank Dr Nadine Aziz of Valerion Therapeutics for acquiring and allowing us to use the immunofluorescence image in Figure I B of Box 2 and for assisting with editing. We thank members of the laboratory of M.S.G. for their support and assistance in critically reviewing this manuscript. M.S.G is funded in part through a sponsored project from Valerion Therapeutics. Additional funding to M.S.G is provided by National Institutes of Health (NIH) grants R01 NS070899 and P01 NS097197, and an Epilepsy Foundation New Therapy Commercialization Grant.

Funders	Funder number
Epilepsy Foundation New Therapy Commercialization
National Institutes of Health (NIH)	P01 NS097197
National Institutes of Health (NIH)
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council	R01NS070899
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council
Valerion Therapeutics

Keywords

Pompe disease
antibody-directed therapies, Lafora disease
antibody–drug conjugate
antibody–enzyme fusion
glycogen

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology

Access to Document

10.1016/j.molmed.2019.08.005

Cite this

@article{444d72285c0248cf8bc7ff27824f73a6,

title = "Antibody-Mediated Enzyme Therapeutics and Applications in Glycogen Storage Diseases",

abstract = "The use of antibodies as targeting molecules or cell-penetrating tools has emerged at the forefront of pharmaceutical research. Antibody-directed therapies in the form of antibody–drug conjugates, immune modulators, and antibody-directed enzyme prodrugs have been most extensively utilized as hematological, rheumatological, and oncological therapies, but recent developments are identifying additional applications of antibody-mediated delivery systems. A novel application of this technology is for the treatment of glycogen storage disorders (GSDs) via an antibody–enzyme fusion (AEF) platform to penetrate cells and deliver an enzyme to the cytoplasm, nucleus, and/or other organelles. Exciting developments are currently underway for AEFs in the treatment of the GSDs Pompe disease and Lafora disease (LD). Antibody-based therapies are quickly becoming an integral part of modern disease therapeutics.",

keywords = "Pompe disease, antibody-directed therapies, Lafora disease, antibody–drug conjugate, antibody–enzyme fusion, glycogen",

author = "Zhengqiu Zhou and Austin, \{Grant L.\} and Robert Shaffer and Armstrong, \{Dustin D.\} and Gentry, \{Matthew S.\}",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",

year = "2019",

month = dec,

doi = "10.1016/j.molmed.2019.08.005",

language = "English",

volume = "25",

pages = "1094--1109",

number = "12",

}

TY - JOUR

T1 - Antibody-Mediated Enzyme Therapeutics and Applications in Glycogen Storage Diseases

AU - Zhou, Zhengqiu

AU - Austin, Grant L.

AU - Shaffer, Robert

AU - Armstrong, Dustin D.

AU - Gentry, Matthew S.

PY - 2019/12

Y1 - 2019/12

N2 - The use of antibodies as targeting molecules or cell-penetrating tools has emerged at the forefront of pharmaceutical research. Antibody-directed therapies in the form of antibody–drug conjugates, immune modulators, and antibody-directed enzyme prodrugs have been most extensively utilized as hematological, rheumatological, and oncological therapies, but recent developments are identifying additional applications of antibody-mediated delivery systems. A novel application of this technology is for the treatment of glycogen storage disorders (GSDs) via an antibody–enzyme fusion (AEF) platform to penetrate cells and deliver an enzyme to the cytoplasm, nucleus, and/or other organelles. Exciting developments are currently underway for AEFs in the treatment of the GSDs Pompe disease and Lafora disease (LD). Antibody-based therapies are quickly becoming an integral part of modern disease therapeutics.

AB - The use of antibodies as targeting molecules or cell-penetrating tools has emerged at the forefront of pharmaceutical research. Antibody-directed therapies in the form of antibody–drug conjugates, immune modulators, and antibody-directed enzyme prodrugs have been most extensively utilized as hematological, rheumatological, and oncological therapies, but recent developments are identifying additional applications of antibody-mediated delivery systems. A novel application of this technology is for the treatment of glycogen storage disorders (GSDs) via an antibody–enzyme fusion (AEF) platform to penetrate cells and deliver an enzyme to the cytoplasm, nucleus, and/or other organelles. Exciting developments are currently underway for AEFs in the treatment of the GSDs Pompe disease and Lafora disease (LD). Antibody-based therapies are quickly becoming an integral part of modern disease therapeutics.

KW - Pompe disease

KW - antibody-directed therapies, Lafora disease

KW - antibody–drug conjugate

KW - antibody–enzyme fusion

KW - glycogen

UR - https://www.scopus.com/pages/publications/85072076351

UR - https://www.scopus.com/pages/publications/85072076351#tab=citedBy

U2 - 10.1016/j.molmed.2019.08.005

DO - 10.1016/j.molmed.2019.08.005

M3 - Review article

C2 - 31522955

AN - SCOPUS:85072076351

SN - 1471-4914

VL - 25

SP - 1094

EP - 1109

JO - Trends in Molecular Medicine

JF - Trends in Molecular Medicine

IS - 12

ER -

Antibody-Mediated Enzyme Therapeutics and Applications in Glycogen Storage Diseases

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this