Evidence map›Paper›PMID 40817303›Full record

Trial reportNature medicine2025

Dual-vector rAAVrh8 gene therapy for GM2 gangliosidosis: a phase 1/2 trial.

Florian Eichler, Oguz I Cataltepe, Rrita Daci, Ajit S Puri, Toloo Taghian, Xuntian Jiang, Mohammed Salman Shazeeb, Anna Kuhn, Asma Hader, Hakki Celik and 26 more

Abstract readClinical Trial, Phase IClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

36 authors.

Florian EichlerDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Oguz I CataltepeDepartment of Neurological Surgery, University of Massachusetts Medical School, Worcester, MA, USA.
Rrita DaciDepartment of Neurological Surgery, University of Massachusetts Medical School, Worcester, MA, USA.
Ajit S PuriDepartment of Neurological Surgery, University of Massachusetts Medical School, Worcester, MA, USA.
Toloo TaghianHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Xuntian JiangDepartment of Medicine, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-9048-7294
Mohammed Salman ShazeebDepartment of Radiology, University of Massachusetts Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-3175-8098
Anna KuhnDepartment of Radiology, University of Massachusetts Medical School, Worcester, MA, USA.
Asma HaderDepartment of Radiology, University of Massachusetts Medical School, Worcester, MA, USA.
Hakki CelikDepartment of Radiology, University of Massachusetts Medical School, Worcester, MA, USA.
Zeynep VardarDepartment of Radiology, University of Massachusetts Medical School, Worcester, MA, USA.
Connor J LewisGlycosphingolipid and Glycoprotein Disorders Unit, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-8204-5848
Rebecca ArtinianHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Amanda NagyDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-8116-4805
Behroze VachhaImage Processing and Analysis Core (iPAC), Department of Radiology, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0001-7462-1422
Robert ThompsonDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Thomas GallagherHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0001-6381-6902
Scot BatemanDepartment of Pediatrics, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Julia ParzychDepartment of Anesthesiology and Perioperative Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Spiro G SpanakisDepartment of Anesthesiology and Perioperative Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Toby A VaughnJnana Therapeutics, Boston, MA, USA.
Kirsten PierTKD Solutions, Spokane, WA, USA.
Erika De BoeverEDB Consulting, Haverford, PA, USA.
Mary-Alice AbbottUniversity of Massachusetts Chan Medical School - Baystate, Baystate Children's Hospital, Springfield, MA, USA.
Eleonora D AmbrosioHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Danielle KokoskiHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Meghan BlackwoodHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Elise DrummondDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Eva-Maria RataiAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Elise L TownsendDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Haley McLaughlinDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Cynthia J TifftGlycosphingolipid and Glycoprotein Disorders Unit, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Allison M KeelerHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-5202-4616
Miguel Sena-EstevesHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0003-0854-0143
Heather L Gray-EdwardsHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA. Heather.GrayEdwards@umassmed.edu.ORCID http://orcid.org/0000-0002-7856-3159
Terence R FlotteHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA. Terry.Flotte@umassmed.edu.ORCID http://orcid.org/0000-0002-8255-0588

Funding

WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI Clay F. Semenkovich · 2013 to 2026
$27.1M
NIDDK NIH HHS P30 DK020579
6 · The paper itself

Abstract

The dual rAAVrh8-HEXA and rAAVrh8-HEXB vector can restore central nervous system hexosaminidase (Hex) enzyme activity, decrease GM2 levels in cerebrospinal fluid and rescue phenotypic consequences of GM2 gangliosidosis, Tay-Sachs and Sandhoff diseases in animal models following simultaneous bi-thalamic (BiT) injections. Following up on an n = 2 expanded access trial, we initiated a phase 1/2, single-dose, dose-escalation of combined BiT, intra-cisterna magna and intrathecal infusion in children with Tay-Sachs and Sandhoff diseases (six infantile, three juvenile). The BiT injection volume and vector dose were doubled between four cohorts, with the lowest dose matching the earlier expanded access trial. Cerebrospinal fluid HexA enzyme activity, serum total Hex activity and GM2 levels showed a dose-dependent biochemical correction of the disease. Serum Hex activity surpassed 40 nmol h

Indexed as

DependovirusGangliosidoses, GM2Genetic TherapyGenetic VectorsSandhoff DiseaseTay-Sachs DiseaseAdolescentbeta-Hexosaminidase alpha ChainChildChild, PreschoolFemaleHumansInfantMalebeta-Hexosaminidase alpha Chain

Identifiers

PMID40817303
PMCPMC12443631

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.