Evidence map›Paper›PMID 40766118›Full record

ArticlemedRxiv : the preprint server for health sciences2025

AAV9 Gene Therapy in GM1 Gangliosidosis Type II: A Phase 1/2 Trial.

Connor J Lewis, Precilla D'Souza, Jean M Johnston, Maria T Acosta, Cristan Farmer, Eva H Baker, Anna Crowell, Yoliann Mojica, Sumaiya Rahman, Lisa Joseph and 22 more

Registry-linked trialAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03952637 (A Phase 1/2 Study of Intravenous Gene Transfer With an AAV9 Vector Expressing Human Beta-galactosidase in Type I and Type II GM1 Gangliosidosis), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03952637 phase1 / phase2recruitingnot on this map

A Phase 1/2 Study of Intravenous Gene Transfer With an AAV9 Vector Expressing Human Beta-galactosidase in Type I and Type II GM1 Gangliosidosis

TypeinterventionalSponsorNational Human Genome Research Institute (NHGRI)Ran2019 to 2028Enrolled54ConditionsLysosomal Diseases, Gangliosidosis, GM1ArmsAAV9-GLB1, Abdominal ultrasound, Rituximab, Sirolimus, Methylprednisolone
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

32 authors.

Connor J LewisOffice of the Clinical Director, National Human Genome Research Institute, Bethesda, MD, USA.ORCID 0000-0002-8204-5848
Precilla D'SouzaOffice of the Clinical Director, National Human Genome Research Institute, Bethesda, MD, USA.
Jean M JohnstonOffice of the Clinical Director, National Human Genome Research Institute, Bethesda, MD, USA.
Maria T AcostaOffice of the Clinical Director, National Human Genome Research Institute, Bethesda, MD, USA.
Cristan FarmerNeurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, Bethesda, MD, USA.ORCID 0000-0001-6878-5199
Eva H BakerDepartment of Diagnostic Radiology, National Institutes of Health Clinical Center, Bethesda, MD, USA.ORCID 0000-0001-7347-2170
Anna CrowellOffice of the Clinical Director, National Human Genome Research Institute, Bethesda, MD, USA.
Yoliann MojicaOffice of the Clinical Director, National Human Genome Research Institute, Bethesda, MD, USA.
Sumaiya RahmanOffice of the Clinical Director, National Human Genome Research Institute, Bethesda, MD, USA.
Lisa JosephNeurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, Bethesda, MD, USA.
Adam HartmanDivision of Clinical Research, National Institute of Neurological Disorders and Stroke, Rockville, MD, USA.
Gilbert VézinaDivision of Diagnostic Imaging and Radiology, Children's National Hospital, Washington DC, USA.
Zenaide QuezadoDepartment of Perioperative Medicine, National Institutes of Health Clinical Center, Bethesda, MD, USA.
Muhammad H YousefDepartment of Perioperative Medicine, National Institutes of Health Clinical Center, Bethesda, MD, USA.
Amelia LuckettDepartment of Perioperative Medicine, National Institutes of Health Clinical Center, Bethesda, MD, USA.
Zeynep VardarDepartment of Radiology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Mohammad Salman ShazeebDepartment of Radiology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Manuela CortiDepartment of Pediatrics, University of Florida, Gainesville, FL, USA.
Meghan BlackwoodHorae Gene Therapy Center and The Li Weibo Institute for Rare Diseases Research, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Kirsten ColemanDepartment of Pediatrics, University of Florida, Gainesville, FL, USA.
Audrey ThurmNeurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, Bethesda, MD, USA.
Erika De BoeverEDB Consulting, Haverford, PA, USA.
William A GahlMedical Genetics Branch, National Human Genome Research Institute, Bethesda, MD, USA.
Barry J ByrneDepartment of Pediatrics, University of Florida, Gainesville, FL, USA.
Terence R FlotteHorae Gene Therapy Center and The Li Weibo Institute for Rare Diseases Research, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Xuntian JiangDepartment of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Amanda L GrossScott-Ritchey Research Center, Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA.
Allison M KeelerHorae Gene Therapy Center and The Li Weibo Institute for Rare Diseases Research, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID 0000-0002-5202-4616
Heather Gray-EdwardsDepartment of Radiology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Douglas R MartinScott-Ritchey Research Center, Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA.
Miguel Sena-EstevesDepartment of Neurology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Cynthia J TifftOffice of the Clinical Director, National Human Genome Research Institute, Bethesda, MD, USA.

Funding

WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI Clay F. Semenkovich · 2013 to 2026
$27.1M
Neurodevelopmental and Behavioral Phenotyping ZICMH002961 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI THURM, AUDREY · 2017 to 2025
$12.6M
Pathogenesis informs therapy in the GM1 and GM2 GangliosidosesZIAHG200409 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI TIFFT, CYNTHIA · 2020 to 2025
$4.1M
Validation of analytical methods for quantification of a pentasaccharide biomarker in efficacy assessment of AVV treatment for GM1 gangliosidosisU01NS114156 · NINDS · WASHINGTON UNIVERSITY · PI JIANG, XUNTIAN · 2021 to 2025
$1.9M
Intramural NIH HHS ZIA HG200409Intramural NIH HHS ZIC MH002961NIDDK NIH HHS P30 DK020579NINDS NIH HHS U01 NS114156
6 · The paper itself

Abstract

Background: GM1 gangliosidosis, caused by biallelic variants in Methods: This phase 1-2 open label dose escalation study utilized a single intravenous administration of adeno-associated virus serotype 9 (AAV9) encoding β-galactosidase in the first nine enrolled Type II GM1 gangliosidosis participants. The primary endpoint was safety after 3 years; secondary and exploratory efficacy outcomes included cerebrospinal fluid (CSF) GM1 ganglioside and β-galactosidase, clinical assessments, and neuroimaging changes. Results: One serious adverse event was attributed to the vector, i.e., vomiting requiring rehospitalization for IV hydration. Serum aspartate and alanine aminotransferase levels increased following gene transfer but returned to baseline by 18 months. Per protocol analysis found stability in Vineland Expressive Communication and Gross Motor and significant declines in Fine Motor and Receptive Communication. Median CGI-Improvement scores at 2 and 3 years after gene transfer were "minimally improved" or "no change". CSF β-galactosidase increased and GM1 ganglioside decreased in all participants. MRI showed improved myelination by differential tractography and declines in cerebral atrophy. MRS showed reduced loss of Conclusions: A single IV infusion of AAV9 encoding β-galactosidase was well-tolerated among the first nine Type II GM1 gangliosidosis participants. Secondary and exploratory outcomes suggested improvements in biochemical markers and neuroimaging and stabilized or reduced rates of developmental deterioration (NCT03952637).

Identifiers

PMID40766118
PMCPMC12324653

What OpenQuestion holds

Textmetadata
LicenceCC0
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.