Evidence map›Paper›PMID 37920238›Full record

ArticleMolecular therapy. Methods & clinical development2023

Awake intracerebroventricular delivery and safety assessment of oligonucleotides in a large animal model.

Hector Ribeiro Benatti, Rachel D Prestigiacomo, Toloo Taghian, Rachael Miller, Robert King, Matthew J Gounis, Ugur Celik, Stephanie Bertrand, Susan Tuominen, Lindsey Bierfeldt and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy. Methods & clinical development, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 32% of its field
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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Genetic therapies for neurological diseases.Pharmacological reviews · 2026
    Review
  2. RNAi-mediated silencing of SOD1 profoundly extends survival and functional outcomes in ALS mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    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

18 authors at 2 institutions in 1 country.

Hector Ribeiro BenattiHorae Gene Therapy Center, UMass Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Rachel D PrestigiacomoHorae Gene Therapy Center, UMass Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Toloo TaghianHorae Gene Therapy Center, UMass Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Rachael MillerDepartment of Endocrinology, UMass Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Robert KingDepartment of Radiology, UMass Chan Medical School, 55 N Lake Ave, Worcester, MA 01655, USA.
Matthew J GounisDepartment of Radiology, UMass Chan Medical School, 55 N Lake Ave, Worcester, MA 01655, USA.
Ugur CelikCenter for Clinical Research, UMass Chan Medical School, 55 N Lake Ave, Worcester MA 01655, USA.
Stephanie BertrandCummings School of Veterinary Medicine, Tufts University, Grafton MA 01536, USA.
Susan TuominenDepartment of Animal Medicine, UMass Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Lindsey BierfeldtDepartment of Animal Medicine, UMass Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Elizabeth ParsleyCummings School of Veterinary Medicine, Tufts University, Grafton MA 01536, USA.
Jillian GallagherHorae Gene Therapy Center, UMass Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Erin F HallHorae Gene Therapy Center, UMass Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Abigail W McElroyHorae Gene Therapy Center, UMass Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Miguel Sena-EstevesHorae Gene Therapy Center, UMass Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Anastasia KhvorovaRNA Therapeutic Institute, UMass Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Neil AroninDepartment of Endocrinology, UMass Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Heather L Gray-EdwardsHorae Gene Therapy Center, UMass Chan Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
University of Massachusetts Chan Medical School · USTufts University · US

Funding

Advancing RNA Therapeutics for Huntington’s DiseaseU01NS114098 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ARONIN, NEIL · 2020 to 2024
$6.7M
Expanding the chemical diversity of therapeutic oligonucleotides to treat neurodegenerative disordersR01NS104022 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ANASTASIA KHVOROVA · 2017 to 2026
$6.0M
Mid-Scale RNA Synthesis, Purification and Quality Control SystemS10OD020012 · OD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA · 2015 to 2015
$563k
NIH HHS S10 OD020012NINDS NIH HHS R01 NS104022NINDS NIH HHS U01 NS114098
6 · The paper itself

Abstract

Oligonucleotide therapeutics offer great promise in the treatment of previously untreatable neurodegenerative disorders; however, there are some challenges to overcome in pre-clinical studies. (1) They carry a well-established dose-related acute neurotoxicity at the time of administration. (2) Repeated administration into the cerebrospinal fluid may be required for long-term therapeutic effect. Modifying oligonucleotide formulation has been postulated to prevent acute toxicity, but a sensitive and quantitative way to track seizure activity in pre-clinical studies is lacking. The use of intracerebroventricular (i.c.v.) catheters offers a solution for repeated dosing; however, fixation techniques in large animal models are not standardized and are not reliable. Here we describe a novel surgical technique in a sheep model for i.c.v. delivery of neurotherapeutics based on the fixation of the i.c.v. catheter with a 3D-printed anchorage system composed of plastic and ceramic parts, compatible with magnetic resonance imaging, computed tomography, and electroencephalography (EEG). Our technique allowed tracking electrical brain activity in awake animals via EEG and video recording during and for the 24-h period after administration of a novel oligonucleotide in sheep. Its anchoring efficiency was demonstrated for at least 2 months and will be tested for up to a year in ongoing studies.

Indexed as

CNS drug administrationCSF drug deliveryi.c.v. catheteri.c.v. injectionlarge animal modeloligonucleotide safety assessmentOmmaya reservoirsiRNA

Identifiers

PMID37920238
PMCPMC10618110
OpenAlexW4387061276

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.