Expanded Access use of Intravenous Gene Transfer with AAV9-GLB1 in a Juvenile GM1 Gangliosidosis Participant
- 1National Human Genome Research Institute (NHGRI)
Abstract
GM1 gangliosidosis is an inherited and progressively neurodegenerative lysosomal storage disorder with no approved therapy. We report 5-year safety and 3-year clinical, biochemical, and neuroimaging efficacy outcomes following expanded-access intravenous AAV9-GLB1 gene therapy in GT01, a 6-10-year-old female with juvenile-onset GM1 gangliosidosis. During participation in a natural history study before gene transfer, GT01 developed seizures, dysarthria, loss of ambulation, and progressive neurodegeneration. She received a single intravenous administration of AAV9-GLB1 at 1.5x1013 vector genomes per kilogram of body weight. Early improvements included the resolution of dysphagia, increased interactions with others, assisted ambulation, and gains in specific domains of adaptive functioning. She was seizure-free without anti-epileptic drugs 18 months post dosing with sustained seizure freedom at the study completion. Cerebrospinal fluid concentrations of GM1 ganglioside and H3N2b (a pentasaccharide biomarker indicative of biochemical improvement in this disorder) concentrations decreased by 50% and {beta}-galactosidase reached normal activity. Brain, thalamic, and net fiber tract volume assessed by differential tractography increased and ventriculomegaly improved three years post-dosing. These results indicate that meaningful benefit can be achieved even in advanced neurologic disease.
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BibTeX
@misc{lewis2026expanded,
title = {{Expanded Access use of Intravenous Gene Transfer with AAV9-GLB1 in a Juvenile GM1 Gangliosidosis Participant}},
author = {C. J. Lewis and H. Akmal and P. D'Souza and J. M. Johnston and S. Ashraf and G. Vezina and S. I. Chipman and M. Blackwood and M. H. Yousef and Z. Quezado and W. A. Gahl and B. J. Byrne and T. R. Flotte and X. R. Jiang and A. Thurm and A. L. Gross and A. Keeler and D. R. Martin and M. Sena-Esteves and H. L. Gray-Edwards and R. Y. Wang and C. J. Tifft},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.04.26361573},
url = {https://www.medrxiv.org/content/10.64898/2026.09.04.26361573v1},
note = {CC0},
}
RIS
TY - UNPB
TI - Expanded Access use of Intravenous Gene Transfer with AAV9-GLB1 in a Juvenile GM1 Gangliosidosis Participant
AU - C. J. Lewis
AU - H. Akmal
AU - P. D'Souza
AU - J. M. Johnston
AU - S. Ashraf
AU - G. Vezina
AU - S. I. Chipman
AU - M. Blackwood
AU - M. H. Yousef
AU - Z. Quezado
AU - W. A. Gahl
AU - B. J. Byrne
AU - T. R. Flotte
AU - X. R. Jiang
AU - A. Thurm
AU - A. L. Gross
AU - A. Keeler
AU - D. R. Martin
AU - M. Sena-Esteves
AU - H. L. Gray-Edwards
AU - R. Y. Wang
AU - C. J. Tifft
PY - 2026
DA - 2026/09/04
PB - medRxiv
DO - 10.64898/2026.09.04.26361573
UR - https://www.medrxiv.org/content/10.64898/2026.09.04.26361573v1
AB - GM1 gangliosidosis is an inherited and progressively neurodegenerative lysosomal storage disorder with no approved therapy. We report 5-year safety and 3-year clinical, biochemical, and neuroimaging efficacy outcomes following expanded-access intravenous AAV9-GLB1 gene therapy in GT01, a 6-10-year-old female with juvenile-onset GM1 gangliosidosis. During participation in a natural history study before gene transfer, GT01 developed seizures, dysarthria, loss of ambulation, and progressive neurodegeneration. She received a single intravenous administration of AAV9-GLB1 at 1.5x1013 vector genomes per kilogram of body weight. Early improvements included the resolution of dysphagia, increased interactions with others, assisted ambulation, and gains in specific domains of adaptive functioning. She was seizure-free without anti-epileptic drugs 18 months post dosing with sustained seizure freedom at the study completion. Cerebrospinal fluid concentrations of GM1 ganglioside and H3N2b (a pentasaccharide biomarker indicative of biochemical improvement in this disorder) concentrations decreased by 50% and {beta}-galactosidase reached normal activity. Brain, thalamic, and net fiber tract volume assessed by differential tractography increased and ventriculomegaly improved three years post-dosing. These results indicate that meaningful benefit can be achieved even in advanced neurologic disease.
ER -