Progress and challenges in intrathecal gene therapy for neurological disorders.

Alexia Kagiava, Xin Chen, Richard S Finkel, Steven J Gray, Kleopas A Kleopa

Abstract readReview

In one paragraph

Review in EBioMedicine, 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

5 authors.

Alexia KagiavaDepartment of Neuroscience, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus; Translational Neurotherapeutics Group, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.

Xin ChenDepartment of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA; Peter O'Donnell Brain Institute, University of Texas Southwestern, Dallas, TX, USA.

Richard S FinkelCentre for Experimental Neurotherapeutics St. Jude Children's Research Hospital, Memphis, TN, USA.

Steven J GrayDepartment of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA; Peter O'Donnell Brain Institute, University of Texas Southwestern, Dallas, TX, USA; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Children's Health Dallas, Dallas, TX, USA; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA; McDermott Centre for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Kleopas A KleopaDepartment of Neuroscience, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus; Center for Neuromuscular Disorders, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus. Electronic address: kleopa@cing.ac.cy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gene therapy for neurological disorders is a rapidly evolving field with many preclinical studies and some successful clinical trials. Selectivity of cell specific targeting, efficiency and safety of administration route, and vector dosing are some of the most challenging aspects that need to be addressed for a successful treatment approach. In clinical practice, intravenous delivery is the most commonly used route of administration of viral vectors but adverse events led to the development of intrathecal delivery as a safer delivery method. Preclinical studies confirm the efficacy of intrathecally injected viral vectors for targeting both the central and peripheral nervous system at lower doses than those systemically-administered, limiting toxicity. Clinical applications of intrathecal gene therapy confirm efficacy and safety in patients. Further preclinical studies are needed to improve current vector capsid and payload technologies, while insights from ongoing clinical trials help to optimise patient selection and immunosuppressive protocols.

Indexed as

Genetic TherapyNervous System DiseasesAnimalsClinical Trials as TopicGene Therapy AgentsGenetic VectorsGene Transfer TechniquesHumansInjections, SpinalAdeno-associated viral vectorCeroid lipofuscinosisCharcot-Marie-Tooth diseaseGene therapyGiant axonal neuropathyIntrathecal deliveryMultiple sulfatase deficiencySpastic paraplegiaSpinal muscular atrophyTay-Sachs disease

Identifiers

PMID42134074

DOI10.1016/j.ebiom.2026.106294

PMCPMC13196305

What OpenQuestion holds

Textmetadata

LicenceCC BY-NC-ND

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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.