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

for PD. We investigated the potential of genetically 5. Conclusion
engineered edible plant tissues as an alternative large-
scale production system that overcomes the high cost To provide a more affordable alternative to the current
of producing rhGAA from CHO cells. Oral-ERT can be ERT, we generated rhGAA produced in tobacco seeds.
safer than infusion and can be ingested in a pill/capsule We observed that tobrhGAA compared favorably and
form at frequent intervals daily to maintain therapeutic was superior to alglucosidase alfa in many aspects. After
levels of the enzyme to achieve long-term clinical efficacy. scaling up, we estimate that the annual cost of treatment
Oral-ERT with tobrhGAA is an innovative approach for an adult living with PD would be $3,000, which is <1%
that overcomes some of the challenges of alglucosidase of the cost of alglucosidase alfa ($250,000 – $650,000/adult
alfa-ERT and provides an effective, safe, and affordable patient/year). Oral-ERT with tobrhGAA is expected to
treatment option as a PMP. 82,87-89,94 Therefore, to provide have significant clinical applications and can lead to a shift
a less expensive alternative, we generated a rhGAA in the current clinical practice paradigm by offering a safe,
produced in tobacco seeds for ERT of PD. We found that stable, and affordable lifelong Oral-ERT for PD in the USA
the tobrhGAA compared favorably and was superior and globally where access to a clinical setting for biweekly
in many aspects to alglucosidase alfa (Table 7). After IV administration of Myozyme is lacking.
scaling up, we estimate that the annual cost for an
adult living with PD would be $3,000, or <1% of the Acknowledgments
cost of alglucosidase alfa, which ranges from $250,000 None.
to $650,000 per adult patient per year depending on
weight. The successful demonstration of Oral-ERT with Funding
tobrhGAA will have significant clinical applications and
shift the current clinical practice paradigm by offering This study was supported in part by the NIH-SBIR Phase
a safe, room temperature stable, and affordable lifelong I grant-Oral-ERT of PD with Tobacco Seed-Derived
Oral-ERT for PD in the USA and worldwide, especially Recombinant Acid Maltase RFA-AR-18-005 grant
in areas where access to a clinical setting for biweekly #1R43AR073522-01.
intravenous administration of Myozyme is lacking. We Conflict of interest
estimate that an adult living with PD will need to take 3
– 4 g/day of tobrhGAA to be equivalent to 0.1% – <1% of The authors declare they have no competing interests.
Myozyme, depending on how it is branded and marketed
to maintain a sustained GAA level of 5% – 10% of normal. Author contributions
A retrospective study of medical and insurance Conceptualization: All authors
records indicated that healthcare costs for patients Formal analysis: All authors
with a rare disease are 3 – 5 times greater than those of Investigation: All authors
patients without a rare disease. Approximately only 10% Methodology: Frank Martiniuk, Adra Mack, Justin
of rare diseases have an FDA-approved therapy, which Martiniuk, Gregory O. Voronin, Shoreh Miller, David
emphasizes the urgent need for more research for earlier Reimer, Nancy Rossi, Leslie Sheppard Bird, Sussan
and more accurate diagnoses of and interventions for Saleh, Ruby Gupta, Mariel Nigro, Peter Meinke,
rare diseases. Most of the 7,000 – 10,000 known rare Benedikt Schoser, Feng Wu, Kam-Meng Tchou-Wong
diseases disproportionately affect children, adolescents, Writing – original draft: All authors
and young adults. Individually, most rare diseases might Writing – review & editing: All authors
affect only a few hundred to a few thousand worldwide.
However, collectively rare diseases are common and affect Ethics approval and consent to participate
an estimated 25 – 30 million patients in the USA. Many of The Institutional Biosafety Committee ratified the project
these diseases are genetic, life-threatening, and challenging
to diagnose and treat. Estimates from commercial and at biosafety level BSL1 containment, and this study was
insurance payers show costs ranged from $8,812 to approved by the Institutional Animal Care and Use
$140,044 for patients with a rare disease compared to Committee at Rutgers, The State University of New Jersey
$5,862 for those without a rare disease. Extrapolating the (number: PROTO201800168).
average cost for the 25 – 30 million patients with rare Consent for publication
diseases in the USA results in a total yearly direct medical
cost of approximately $400 billion. 174 Not applicable.

Volume 4 Issue 1 (2025) 14 doi: 10.36922/gpd.1760