Evidence map›Paper›PMID 39192584›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024

A minimally invasive endovascular approach to the cerebellopontine angle cistern enables broad CNS biodistribution of scAAV9-CB-GFP.

Hector Ribeiro Benatti, Vania Anagnostakou, Toloo Taghian, Erin F Hall, Sarah Nath, Carl B Heilman, Brandon M Beneduce, Anita Leporati, Christopher Raskett, Mark Epshtein and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–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

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
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

14 authors.

Hector Ribeiro BenattiHorae Gene Therapy Center, UMass Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Vania AnagnostakouNew England Center for Stroke Research, Department of Radiology, UMass Chan Medical School, 55 N Lake Avenue, Worcester, MA 01655, USA.
Toloo TaghianHorae Gene Therapy Center, UMass Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA; New England Center for Stroke Research, Department of Radiology, UMass Chan Medical School, 55 N Lake Avenue, Worcester, MA 01655, USA.
Erin F HallHorae Gene Therapy Center, UMass Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Sarah NathHorae Gene Therapy Center, UMass Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Carl B HeilmanTufts Medical Center, 800 Washington Street, Boston, MA 02111, USA.
Brandon M BeneduceCereVasc, Inc., 100 1(st) Avenue, Suite 403, Boston, MA 02129, USA.
Anita LeporatiNew England Center for Stroke Research, Department of Radiology, UMass Chan Medical School, 55 N Lake Avenue, Worcester, MA 01655, USA.
Christopher RaskettNew England Center for Stroke Research, Department of Radiology, UMass Chan Medical School, 55 N Lake Avenue, Worcester, MA 01655, USA.
Mark EpshteinNew England Center for Stroke Research, Department of Radiology, UMass Chan Medical School, 55 N Lake Avenue, Worcester, MA 01655, USA.
Robert KingNew England Center for Stroke Research, Department of Radiology, UMass Chan Medical School, 55 N Lake Avenue, Worcester, MA 01655, USA.
Matthew J GounisNew England Center for Stroke Research, Department of Radiology, UMass Chan Medical School, 55 N Lake Avenue, Worcester, MA 01655, USA.
Adel M MalekTufts Medical Center, 800 Washington Street, Boston, MA 02111, USA. Electronic address: adel.malek@tuftsmedicine.org.
Heather L Gray-EdwardsHorae Gene Therapy Center, UMass Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA; New England Center for Stroke Research, Department of Radiology, UMass Chan Medical School, 55 N Lake Avenue, Worcester, MA 01655, USA. Electronic address: heather.grayedwards@umassmed.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neurological disorders pose a challenge for targeted therapy due to restricted access of therapeutic agents to the central nervous system (CNS). Current methods are limited by procedure-related risks, invasiveness, and insufficient CNS biodistribution. A novel percutaneous transvenous technology, currently in clinical trials for communicating hydrocephalus, offers a minimally invasive approach by providing endovascular access to the cerebrospinal fluid-filled cerebellopontine angle (CPA) cistern. We hypothesized that drug delivery to the CPA cistern could yield widespread CNS distribution. Using an ovine model, we compared the biodistribution of scAAV9-CB-GFP following CPA cistern infusion with previously reported cisterna magna (CM) administration. Targeting both the CPA cistern and CM in sheep, we employed a lumbar spine-inserted microcatheter under fluoroscopy. CPA delivery of AAV9 demonstrated biodistribution and transduction in the cerebral cortices, striatum, thalamus, midbrain, cerebellum, and spinal cord, with minor liver distribution comparable to CM. The favorable safety profile in humans with hydrocephalus suggests that percutaneous endovascular injection into the CPA could offer a clinically safer and minimally invasive delivery system for CNS gene and cell-based therapies.

Indexed as

Cerebellopontine AngleDependovirusGenetic VectorsGreen Fluorescent ProteinsAnimalsCentral Nervous SystemCisterna MagnaEndovascular ProceduresGenetic TherapyGene Transfer TechniquesHumansSheepTissue DistributionGreen Fluorescent Proteinscerebellopontine angle cisterncisterna magnaCNS drug administrationCSF drug deliverylarge animal modeltransvascular catheter

Identifiers

PMID39192584
PMCPMC11489529

What OpenQuestion holds

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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.