Evidence map›Paper›PMID 26055150›Full record

ArticleJournal of the Association for Research in Otolaryngology : JARO2015

Hearing Loss and Otopathology Following Systemic and Intracerebroventricular Delivery of 2-Hydroxypropyl-Beta-Cyclodextrin.

Scott Cronin, Austin Lin, Kelsey Thompson, Mark Hoenerhoff, R Keith Duncan

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

Article in Journal of the Association for Research in Otolaryngology : JARO, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.4field-weighted citation impact, top 13% 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

19 citing papers in PubMed, 39 citations in OpenAlex.

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  16. Early experience with compassionate use of 2 hydroxypropyl-beta-cyclodextrin for Niemann-Pick type C disease: review of initial published cases.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2017
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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 at 2 institutions in 1 country.

Scott CroninDepartment of Otolaryngology-Head and Neck Surgery, University of Michigan, 1500 East Medical Center Drive, Taubman Clinic 1A, Ann Arbor, MI, 48109, USA.
Austin LinDepartment of Otolaryngology-Head and Neck Surgery, Kresge Hearing Research Institute, University of Michigan, 1150 West Medical Center Drive, 5323 Medical Science Building I, Ann Arbor, MI, 48109-5616, USA.
Kelsey ThompsonDepartment of Otolaryngology-Head and Neck Surgery, Kresge Hearing Research Institute, University of Michigan, 1150 West Medical Center Drive, 5323 Medical Science Building I, Ann Arbor, MI, 48109-5616, USA.
Mark HoenerhoffUnit for Laboratory Animal Medicine, University of Michigan, North Campus Research Complex, Building 36, Room 178, 2800 Plymouth Road, Ann Arbor, MI, 48103, USA.
R Keith DuncanDepartment of Otolaryngology-Head and Neck Surgery, University of Michigan, 1500 East Medical Center Drive, Taubman Clinic 1A, Ann Arbor, MI, 48109, USA. rkduncan@umich.edu.
University of Michigan–Ann Arbor · USA. Alfred Taubman Health Care Center · US

Funding

Scientific Synergy CoreP30DC005188 · NIDCD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SCHACHT, JOCHEN · 2002 to 2016
$10.3M
NIDCD NIH HHS P30 DC005188
6 · The paper itself

Abstract

Cyclodextrins are simple yet powerful molecules widely used in medicinal formulations and industry for their ability to stabilize and solubilize guest compounds. However, recent evidence shows that 2-hydroxypropyl-β-cyclodextrin (HPβCD) causes severe hearing loss in mice, selectively killing outer hair cells (OHC) within 1 week of subcutaneous drug treatment. In the current study, the impact of HPβCD on auditory physiology and pathology was explored further as a function of time and route of administration. When administered subcutaneously or directly into cerebrospinal fluid, single injections of HPβCD caused up to 60 dB threshold shifts and widespread OHC loss in a dose-dependent manner. Combined dosing caused no greater deficit, suggesting a common mode of action. After drug treatment, OHC loss progressed over time, beginning in the base and extending toward the apex, creating a sharp transition between normal and damaged regions of the cochlea. Administration into cerebrospinal fluid caused rapid ototoxicity when compared to subcutaneous delivery. Despite the devastating effect on the cochlea, HPβCD was relatively safe to other peripheral and central organ systems; specifically, it had no notable nephrotoxicity in contrast to other ototoxic compounds like aminoglycosides and platinum-based drugs. As cyclodextrins find expanding medicinal applications, caution should be exercised as these drugs possess a unique, poorly understood, ototoxic mechanism.

Indexed as

2-Hydroxypropyl-beta-cyclodextrinAnimalsAuditory Thresholdbeta-CyclodextrinsDose-Response Relationship, DrugHair Cells, Auditory, OuterHearing LossInjections, IntraventricularMice2-Hydroxypropyl-beta-cyclodextrinbeta-Cyclodextrinscochleacyclodextrindrug deliveryhearing lossototoxicity

Identifiers

PMID26055150
PMCPMC4569609
OpenAlexW566428193

What OpenQuestion holds

Textmetadata
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.