GC801-enabled AAV gene therapy in a neonate with Pompe disease

Abstract

We report a neonate with IOPD who had high pre-existing anti-AAV9 antibody titers, which precluded eligibility for AAV9-mediated gene therapy (GC301). Preconditioning with a single dose of the IgG-degrading enzyme GC801 (0.2 mg/kg) safely reduced serum IgG from 6.25 g/L to a nadir of 0.72 g/L within 5 days. This pharmacological window facilitated successful GC301 vector transduction, driving a robust increase in GAA activity to 19.38 mmol/L/16h by day 84. Crucially, no adverse events beyond the underlying IOPD were observed. Our findings support the potential utility of GC801 as an agent to overcome pre-existing humoral barriers in neonatal gene therapy candidates.

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BibTeX RIS

BibTeX

@misc{chen2026gc801enabled,
  title = {{GC801-enabled AAV gene therapy in a neonate with Pompe disease}},
  author = {J. Chen and W. Ma and H. Qi and X. Ma and Y. He and L. He and Y. Ke and L. Zhuang and X. Jiang and J. Wang and J. Xu and Y. Xia and J. Zhou and Y. Wang and X. Dong and X. Wu and Z. Feng},
  howpublished = {medRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.23.26363499},
  url = {https://www.medrxiv.org/content/10.64898/2026.09.23.26363499v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - GC801-enabled AAV gene therapy in a neonate with Pompe disease
AU  - J. Chen
AU  - W. Ma
AU  - H. Qi
AU  - X. Ma
AU  - Y. He
AU  - L. He
AU  - Y. Ke
AU  - L. Zhuang
AU  - X. Jiang
AU  - J. Wang
AU  - J. Xu
AU  - Y. Xia
AU  - J. Zhou
AU  - Y. Wang
AU  - X. Dong
AU  - X. Wu
AU  - Z. Feng
PY  - 2026
DA  - 2026/09/23
PB  - medRxiv
DO  - 10.64898/2026.09.23.26363499
UR  - https://www.medrxiv.org/content/10.64898/2026.09.23.26363499v1
AB  - We report a neonate with IOPD who had high pre-existing anti-AAV9 antibody titers, which precluded eligibility for AAV9-mediated gene therapy (GC301). Preconditioning with a single dose of the IgG-degrading enzyme GC801 (0.2 mg/kg) safely reduced serum IgG from 6.25 g/L to a nadir of 0.72 g/L within 5 days. This pharmacological window facilitated successful GC301 vector transduction, driving a robust increase in GAA activity to 19.38 mmol/L/16h by day 84. Crucially, no adverse events beyond the underlying IOPD were observed. Our findings support the potential utility of GC801 as an agent to overcome pre-existing humoral barriers in neonatal gene therapy candidates.
ER  -

Abstract

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