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Gene & Protein in Disease Oral-ERT in PD knockout mice with tobrhGAA

Figure 7. Pharmacokinetics of oral-enzyme replacement therapy in the serum of GAA KO mice. Serum clearance rate in GAA KO mice treated with a
3× dose (75 μg of tobrhGAA) or whole seeds was determined at 0, 1, 2, 4, 6, 8, 10, 12, 24, and 48 h for tobrhGAA activity (mean ± standard deviation)
Abbreviations: GAA: Acid a-glucosidase; h: Hours; tobrhGAA: Tobacco seeds expressing human acid a-glucosidase; KO: Knockout.

Figure 8. Pharmacokinetics of Oral-enzyme replacement therapy in the urine of GAA KO mice. The urine clearance rate in GAA KO mice treated with
a 3× dose (75 mg of tobrhGAA) or whole seeds was determined at 0, 1, 2, 4, 6, 8, 10, 12, 24, and 48 h for tobrhGAA activity (mean ± standard deviation)
Abbreviations: GAA: Acid a-glucosidase; h: Hours; tobrhGAA: Tobacco seeds expressing human acid a-glucosidase; KO: Knockout.

for cardiac and 12 mg/kg for skeletal muscle. Therefore, and functional defects and established a new perspective
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oral formulations of ground tobrhGAA seeds will allow for the treatment of PD. Lim et al. 147 reactivated mTOR
18
patients to ingest treatments daily in single or multiple in PD mice through TSC knockdown, resulting in the
doses conveniently at home to sustain a therapeutic dose reversal of muscle atrophy and removal of autophagic
of enzyme activity and to improve their quality of life. buildup, as well as revealing that aberrant mTOR signaling
can be reversed by arginine alone. 146-148 Jung et al. 149,150
Investigators are studying the role of autophagy, 19,145-147
an intracellular system for delivering portions of cytoplasm produced and characterized a rhGAA in a transgenic rice
and damaged organelles to lysosomes for degradation and cell suspension culture with high-mannose glycans, which
recycling in PD and the reduction of glycogen in skeletal was similar to the CHO-derived hGAA.
muscle. A GAA and glycogen synthase 1 dual KO mouse Sariyatun et al. 151 produced a human GAA with
model exhibited a profound reduction of glycogen in a paucimannose structure (Man3GlcNAc2M3) in a
the heart and skeletal muscles, a decrease in lysosomal glycoengineered Arabidopsis alg3 cell line. Recently,
autophagic buildup, and correction of cardiomegaly. Cohen et al. 152,153 reported the safety and efficacy of the
The abnormalities in glucose metabolism were corrected in utero ERT of a fetus with CRIM-neg IOPD. The family
in the double-KO mice that demonstrated long-term history was positive for IOPD with cardiomyopathy in two
elimination of muscle glycogen synthesis, which resulted previously affected deceased siblings. After receiving six in
in a significant improvement in the structural, metabolic, utero ERT through the umbilical vein starting at 24 weeks

Volume 4 Issue 1 (2025) 12 doi: 10.36922/gpd.1760