Evidence map›Paper›PMID 39009597›Full record

ArticleNature communications2024

A combination treatment based on drug repurposing demonstrates mutation-agnostic efficacy in pre-clinical retinopathy models.

Henri Leinonen, Jianye Zhang, Laurence M Occelli, Umair Seemab, Elliot H Choi, Luis Felipe L P Marinho, Janice Querubin, Alexander V Kolesnikov, Anna Galinska, Katarzyna Kordecka and 13 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

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

  1. Pooled it
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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

23 authors.

Henri LeinonenSchool of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Yliopistonranta 1C, 70211, Kuopio, Finland. henri.leinonen@uef.fi.ORCID 0000-0002-0388-832X
Jianye ZhangGavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, 92697, USA.
Laurence M OccelliSmall Animal Clinical Sciences, Michigan State University, East Lansing, MI, 48824, USA.
Umair SeemabSchool of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Yliopistonranta 1C, 70211, Kuopio, Finland.
Elliot H ChoiGavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, 92697, USA.
Luis Felipe L P MarinhoSmall Animal Clinical Sciences, Michigan State University, East Lansing, MI, 48824, USA.
Janice QuerubinSmall Animal Clinical Sciences, Michigan State University, East Lansing, MI, 48824, USA.
Alexander V KolesnikovGavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, 92697, USA.
Anna GalinskaInternational Centre for Translational Eye Research, Warsaw, Poland.ORCID 0000-0003-4570-0425
Katarzyna KordeckaInternational Centre for Translational Eye Research, Warsaw, Poland.
Thanh HoangDepartment of Ophthalmology, Department of Cell & Developmental Biology, Ann Arbor, MI, 48105, USA.
Dominik LewandowskiGavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, 92697, USA.ORCID 0000-0002-2233-5501
Timothy T LeeGavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, 92697, USA.ORCID 0009-0009-7759-1519
Elliott E EinsteinGavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, 92697, USA.
David E EinsteinGavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, 92697, USA.
Zhiqian DongGavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, 92697, USA.
Philip D KiserGavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, 92697, USA.ORCID 0000-0003-1184-9539
Seth BlackshawDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.ORCID 0000-0002-1338-8476
Vladimir J KefalovGavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, 92697, USA.
Marcin TabakaInternational Centre for Translational Eye Research, Warsaw, Poland.ORCID 0000-0002-6166-2820
Andrzej FoikInternational Centre for Translational Eye Research, Warsaw, Poland.ORCID 0000-0003-1110-9223
Simon M Petersen-JonesSmall Animal Clinical Sciences, Michigan State University, East Lansing, MI, 48824, USA.ORCID 0000-0002-7410-2304
Krzysztof PalczewskiGavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, CA, 92697, USA. kpalczew@uci.edu.ORCID 0000-0002-0788-545X

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
STRUCTURAL STUDIES OF ARRESTINSR01EY009339 · NEI · UNIVERSITY OF WASHINGTON · PI KISER, PHILIP DAVID, PALCZEWSKI, KRZYSZTOF · 1992 to 2025
$16.0M
Precision genome editing in vivo to treat retinal diseasesR01EY034501 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Audrone Lapinaite, Krzysztof Palczewski · 2023 to 2026
$3.9M
NEI UCI Center Core Grant for Vision ResearchP30EY034070 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Vladimir Jivkov Kefalov · 2022 to 2026
$3.7M
Retinoid cycles and retinal disease treatmentI01BX004939 · VA · VETERANS HEALTH ADMINISTRATION · PI KISER, PHILIP DAVID · 2020 to 2025
–
Academy of Finland (Suomen Akatemia) 346295BLRD VA I01 BX004939NCI NIH HHS P30 CA062203NEI NIH HHS P30 EY034070NEI NIH HHS R01 EY009339NEI NIH HHS R01 EY034501
6 · The paper itself

Abstract

Inherited retinopathies are devastating diseases that in most cases lack treatment options. Disease-modifying therapies that mitigate pathophysiology regardless of the underlying genetic lesion are desirable due to the diversity of mutations found in such diseases. We tested a systems pharmacology-based strategy that suppresses intracellular cAMP and Ca2+ activity via G protein-coupled receptor (GPCR) modulation using tamsulosin, metoprolol, and bromocriptine coadministration. The treatment improves cone photoreceptor function and slows degeneration in Pde6βrd10 and RhoP23H/WT retinitis pigmentosa mice. Cone degeneration is modestly mitigated after a 7-month-long drug infusion in PDE6A-/- dogs. The treatment also improves rod pathway function in an Rpe65-/- mouse model of Leber congenital amaurosis but does not protect from cone degeneration. RNA-sequencing analyses indicate improved metabolic function in drug-treated Rpe65-/- and rd10 mice. Our data show that catecholaminergic GPCR drug combinations that modify second messenger levels via multiple receptor actions provide a potential disease-modifying therapy against retinal degeneration.

Indexed as

Disease Models, AnimalDrug RepositioningRetinitis PigmentosaAnimalsBromocriptineCalciumcis-trans-IsomerasesCyclic AMPCyclic Nucleotide Phosphodiesterases, Type 6DogsDrug Therapy, CombinationFemaleHumansLeber Congenital AmaurosisMaleMiceBromocriptineCalciumcis-trans-IsomerasesCyclic AMPCyclic Nucleotide Phosphodiesterases, Type 6Receptors, G-Protein-CoupledRetinoid Isomerohydrolase

Identifiers

PMID39009597
PMCPMC11251169

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.