Page 87 - GPD-4-1

Gene & Protein in Disease

ORIGINAL RESEARCH ARTICLE
Pre-clinical studies for oral enzyme replacement

therapy in Pompe disease knockout mice with
tobacco seeds expressing human GAA

Frank Martiniuk * , Adra Mack , Justin Martiniuk , Gregory O. Voronin ,
1,2
3
1,2
1,2
4
6
7
Shoreh Miller , David Reimer , Nancy Rossi , Leslie Sheppard Bird ,
5
7
Sussan Saleh , Ruby Gupta , Mariel Nigro , Peter Meinke 8 , Benedikt Schoser ,
7
7
8
9
Feng Wu , Angelo Kambitsis , John Arvanitopoulos , Elena Arvanitopoulos ,
1,2
1,2
1,2
10
11
Pavlos Arvanitopoulos , Alexander Demetriades , and
Kam-Meng Tchou-Wong 12
1 JME Group Associates, Inc, 24 Ford Lane, Roseland, NJ, United States of America
2 PsychoGenetics Center, 215 College Rd., Lab 213, Paramus, NJ, United States of America
3 In Vivo Research Services Rutgers, The State University of New Jersey, United States of America
4 Department of Pediatric, RWJMS Director, In Vivo Research Services (IVRS) Rutgers University
Animal Care U (RUAC) Rutgers, the State University of New Jersey Rm 017, CABM 679 Hoes Lane
West Piscataway, NJ, United States of America
Abstract
Genetic deficiency of acid a-glucosidase (GAA) results in Pompe disease (PD)
encompassing four clinical subtypes of varying severity. Our objective is to develop
*Corresponding author: an innovative and affordable approach for enzyme replacement therapy (ERT)
Frank Martiniuk through oral administration (Oral-ERT) to maintain a sustained therapeutic level of
(frank.martiniuk@gmail.com) enzyme daily to improve treatment efficacy. Tobacco seeds contain the metabolic
Citation: Martiniuk F, machinery compatible with mammalian glycosylation-phosphorylation. We have
Mack A, Martiniuk J, et al. Pre- shown that transgenic tobacco seeds expressing human GAA (tobrhGAA) were
clinical studies for oral enzyme
replacement therapy in Pompe enzymatically active and can correct the enzyme deficiency in cultured cells and
disease knockout mice with tobacco in GAA knockout (GAAKO) mice administered IP. We have extended these studies in
seeds expressing human GAA. PD KO mice with ground tobrhGAA seeds. Briefly, in PD knockout mice, Oral-ERT
Gene Protein Dis. 2025;4(1):1760.
doi: 10.36922/gpd.1760 with ground tobrhGAA seeds showed a significant reversal of fore-limb and hind-
limb muscle weakness, increased motor coordination/balance/strength/mobility,
Received: September 5, 2023
1st revised: May 1, 2024 improved spontaneous learning, increased GAA activity in tissues, reduced glycogen
2nd revised: June 18, 2024 in tissues and negligible serum titers to GAA. Pharmacokinetics showed maximum
Accepted: June 20, 2024 serum GAA concentration at 8 – 10 h and peak urine excretion at 10 – 12 h post-
Published online: January 2, 2025
administration. The tobrhGAA was taken up in PD fibroblast, lymphoid, and myoblast
Copyright: © 2025 Author(s). cells. Enzyme kinetics compared favorably to hGAA, plus alglucosidase alfa or other
This is an Open-Access article recombinant human GAAs for K , V , pH optima, thermal heat stability, and IC for
distributed under the terms of the m max 50
Creative Commons Attribution inhibitors. The tobrhGAA in seeds was stable for 15 years at room temperature. Thus,
License, permitting distribution, Oral-ERT with ground tobrhGAA seeds is an innovative approach that overcomes
and reproduction in any medium, some of the challenges of alglucosidase alfa-ERT and provides a more effective, safe,
provided the original work is
properly cited. and significantly less expensive treatment.
Publisher’s Note: AccScience
Publishing remains neutral with Keywords: Recombinant human acid maltase; Transgenic tobacco plants; Pompe
regard to jurisdictional claims in
published maps and institutional disease; Oral enzyme replacement
affiliations.

Volume 4 Issue 1 (2025) 1 doi: 10.36922/gpd.1760