Evidence map›Paper›PMID 42025166›Full record

ArticleCell reports. Medicine2026

AAV-based gene therapy with modified HEXB confers lasting therapeutic benefits in GM2 gangliosidosis models.

Keisuke Kitakaze, Yukiya Ohnishi, Daisuke Tsuji, Ryosuke Watanabe, Nijiho Kamori, Yuko Katakai, Hiroaki Shibata, Sota Yoshizawa, Mika Ito, Naomi Takino and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Keisuke KitakazeDepartment of Pharmacology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
Yukiya OhnishiDepartment of Medicinal Biotechnology, Graduate School of Pharmaceutical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima 770-8505, Japan.
Daisuke TsujiDepartment of Medicinal Biotechnology, Graduate School of Pharmaceutical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima 770-8505, Japan; Department of Medicinal Biotechnology, Faculty of Pharmaceutical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima 770-8505, Japan.
Ryosuke WatanabeDepartment of Medicinal Biotechnology, Graduate School of Pharmaceutical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima 770-8505, Japan.
Nijiho KamoriDepartment of Medicinal Biotechnology, Faculty of Pharmaceutical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima 770-8505, Japan.
Yuko KatakaiThe Corporation for Production and Research of Laboratory Primates, 1-16-2 Sakura, Tsukuba, Ibaraki 305-0003, Japan.
Hiroaki ShibataThe Corporation for Production and Research of Laboratory Primates, 1-16-2 Sakura, Tsukuba, Ibaraki 305-0003, Japan.
Sota YoshizawaONODERA GT Pharma, Inc., 3-25-22 Tonomachi, Kawasaki, Kanagawa 210-0821, Japan.
Mika ItoDivision of Neurological Gene Therapy, Center for Open Innovation, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
Naomi TakinoDivision of Neurological Gene Therapy, Center for Open Innovation, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
Shin-Ichi MuramatsuONODERA GT Pharma, Inc., 3-25-22 Tonomachi, Kawasaki, Kanagawa 210-0821, Japan; Division of Neurological Gene Therapy, Center for Open Innovation, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
Kohji ItohDepartment of Medicinal Biotechnology, Graduate School of Pharmaceutical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima 770-8505, Japan; Department of Medicinal Biotechnology, Faculty of Pharmaceutical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima 770-8505, Japan; Division of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. Electronic address: kitoh@tokushima-u.ac.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

GM2 gangliosidoses, including Tay-Sachs (TSD) and Sandhoff (SD) diseases, are lysosomal storage disorders with neurological manifestations caused by the excessive accumulation of GM2 ganglioside due to the deficiency of the β-hexosaminidase A (HexA). Although gene therapy approaches are underway, concerns regarding efficacy and safety remain. Here, we evaluate a tyrosine-mutant adeno-associated virus serotype 9 (AAV9/3) vector encoding modified HEXB (modHEXB) wherein nine amino acid residues are substituted from HEXA. The intracerebroventricular administration of AAV9/3-modHEXB in SD mice results in modHexB expression in the brain, reduces GM2 accumulation, and attenuates neuroinflammation. Furthermore, AAV9/3-modHEXB rescues motor function, and longer lifespan in SD mice. In addition, intrathecal administration in non-human primates and rats demonstrates broad biodistribution and an overall favorable safety profile. These findings support the translational potential of AAV9/3-modHEXB as a gene therapy approach for TSD and SD.

Indexed as

beta-Hexosaminidase beta ChainDependovirusGangliosidoses, GM2Genetic TherapyAnimalsBrainDisease Models, AnimalGene Therapy AgentsGenetic VectorsG(M2) GangliosideHumansMaleMiceRatsbeta-Hexosaminidase beta ChainG(M2) Gangliosideadeno-associated virusgene therapyGM2 gangliosidosisGT0005Xintrathecal administrationlysosomal storage disordersneurodegenerative diseaseSandhoff diseaseTay-Sachs diseasetranslational study

Identifiers

PMID42025166
PMCPMC13198282

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.