Expanded Access use of Intravenous Gene Transfer with AAV9-GLB1 in a Juvenile GM1 Gangliosidosis Participant
Year: 2026
Type: preprint
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 1.5×10 13 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 β-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.
Source: medRxiv
Authors: Connor J. Lewis, Hera Akmal, Precilla D’Souza, Jean M. Johnston, Sumaiya Ashraf, Gilbert Vezina, Selby I. Chipman, Meghan Blackwood, Muhammad H. Yousef, Zenaide Quezado, William A. Gahl, Barry J. Byrne, Terence R. Flotte, Xuntian Jiang, Audrey Thurm, Amanda L. Gross, Allison M. Keeler, Douglas R. Martin, Miguel Sena-Esteves, Heather L. Gray-Edwards, Raymond Y. Wang, Maria T. Acosta, Cynthia J. Tifft
Institutions: University of Massachusetts Chan Medical School, National Human Genome Research Institute, Children's National, National Institutes of Health, National Institutes of Health Clinical Center, University of Florida, Washington University in St. Louis, National Institute of Mental Health, Auburn University, Children's Hospital of Orange County, University of California, Irvine
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Health and Human Services, National Institutes of Health, Washington University School of Medicine in St. Louis, National Institute of Mental Health, National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke
Awards: G1804974985, G2549522608, G2701512441, G4904263898, G5171416653, Genetic epidemiology of prostate cancer, Using Ethics and User-Centered Design to Create Templates for EHR-Mediated Return of Genetic Test Results, G719812709, G7997475032, G9000153645, Pathogenesis Informs Therapy for Glycosphingolipid and Glycoprotein Disorders, Medical Scientist Training at UMCMS, Validation of analytical methods for quantification of a pentasaccharide biomarker in efficacy assessment of AVV treatment for GM1 gangliosidosis, Neurodevelopmental and Behavioral Phenotyping, Diabetes Research Center
OpenAlex ID: W7212113283