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

Table 7. Comparison of Myozyme and tobacco seeds
Pancreas 0.084±0.05 0.14±0.14 P≤0.28 0.45±1.0 P≤0.02 0.67±0.5 44 expressing human acid a‑glucosidase
Issues with the current
addresses these issues
therapy (Myozyme) Our Oral‑ERT with tobrhGAA
Spleen 0.015±0.007 0.022±0.014 P≥0.21 0.07±0.11 P≥0.06 1.06±1.4 4 • Inefficient uptake • Efficient uptake in appropriate tissues
• Transient nature every 2
• Daily Oral‑ERT
weeks
variable
SI‑I 0.71±0.43 1.54±0.67 P≤0.07 5.1±22 P≤0.0.1 3.3±0.65 99 • Glycogen reduction is a • Glycogen reduction
• Autophagic and lipofuscin • Autophagic and lipofuscin
accumulation accumulation to be determined
SI‑J 0.94±0.7 1.83±1.38 P≥0.15 6±47 P≤0.12 3.47±6.1 112 • Immune response • Immune response minimized
• High cost
• Projected lower cost of plant‑made
pharmaceuticals (1% – 10% of current
therapy depending on the level of
SI‑D 0.4±0.22 1.57±0.58 P≥0.007 2±6.5 P≤0.09 2.68±3.6 67 • Residual effective level • Sustained daily increased residual GAA
purification needed)
level
0.012±0.007 0.023±0.05 P≤0.12 0.05±0.33 P≤0.1 0.73±0.33 5 • Requires refrigeration and • Extremely stable at room temperature
Brain a clinic visit for many years, ERT can be

self-administered at home and no
refrigeration is required
Diaphragm 0.045±0.03 0.11±0.043 P≤0.07 0.2±0.21 P≤0.05 0.38±0.49 40 Abbreviations: tobrhGAA: Tobacco seeds expressing human acid
a-glucosidase; ERT: Enzyme replacement therapy.

normal postnatal cardiac and age-appropriate motor
Lung 0.094±0.07 0.15±0.036 P≤0.22 0.3±0.71 P≤0.1 0.31±0.2 74 gestation and standard postnatal therapy, the patient had
functions, was meeting the developmental milestones, had
normal biomarker levels, and was feeding and growing
153,154
Kidney 0.085±0.09 0.3±0.24 P≤0.11 0.78±3.1 P≤0.01 1.67±0.95 41 well at 13 months.
Seeds may be a better vehicle for Oral-ERT of
lysosomal diseases, such as PD, compared with an
Hindlimb tibialis anterior muscle 0.018±0.0039 0.053±0.067 P≤0.13 0.08±0.29 P≤0.05 0.71±0.38 10 Abbreviations: GAA: Acid a-glucosidase; KO: Knockout; NAG: Neutral a-glucosidase; Tx: Treated; WT: Wild-type. tissues and organelles – contain the metabolic machinery
intravenous delivery system. Seeds – but not other plant
required for the correct glycosylation, processing,
phosphorylation, and synthesis of complex enzymes and
Table 6. Steady‑state GAA levels in the treated tissues
proteins, as enzymes or proteins are protected or shielded
Heart 0.06±0.03 0.1±0.014 P≤0.15 0.2±0.21 P≤0.16 0.5±0.25 60 from digestion in the stomach and small intestine and
can be administered daily in single and multiple doses,
and seeds provide long-term stable storage of the
recombinant enzymes. Several biotechnology companies
Liver 0.073±0.05 0.52±0.44 P≤0.09 0.64±1.6 P≤0.038 6.7±4 15 have tried to mass produce a rhGAA using different
platforms. Prompted by studies of oral formulations of
edible tissues in broccoli sprouts, corn/maize, pea, rice,
(mean±standard deviation) including vaccination to induce effective mucosal
tobacco, and tomato for pharmaceutical applications

immune tolerance and immune reactions, GI, bacterial/
viral infections, allergies, asthma, diabetes, endocrine-
associated diseases, hypersensitivity, elevated BP, cholera,
GAA/NAG (P=Tx versus mock) GAA KO mock GAA KO Tx 50 mg GAA KO Tx 150 mg WT-129/C57 % WT leucopenia, cancer, and RA, 127,154-173 we hypothesized

that rhGAA from edible plant tissues will offer a cost-
effective, innovative and safe strategy for Oral-ERT

Volume 4 Issue 1 (2025) 13 doi: 10.36922/gpd.1760