Evidence map›Paper›PMID 40298667›Full record

ArticleAntioxidants (Basel, Switzerland)2025

Evaluation of Additive Neuroprotective Effect of Combination Therapy for Parkinson's Disease Using In Vitro Models.

Alexander Shtilbans, Elise Esneault, Florian Simon, Joseph R Mazzulli, Drew J Quiriconi, Dror Rom, Wolfgang E Reintsch, Andrea I Krahn, Thomas M Durcan

Abstract read
In one paragraph

Article in Antioxidants (Basel, Switzerland), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  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

9 authors.

Alexander ShtilbansDepartment of Neurology, Hospital for Special Surgery, New York, NY 10021, USA.ORCID 0000-0002-3159-8637
Elise EsneaultPorsolt Research Laboratory, 53940 Le Genest-Saint-Isle, France.
Florian SimonPorsolt Research Laboratory, 53940 Le Genest-Saint-Isle, France.
Joseph R MazzulliDepartment of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Drew J QuiriconiDepartment of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Dror RomProsoft Clinical, Chesterbrook, PA 19087, USA.
Wolfgang E ReintschThe Neuro's Early Drug Discovery Unit (EDDU), McGill University, Montreal, QC H3A 2B4, Canada.
Andrea I KrahnThe Neuro's Early Drug Discovery Unit (EDDU), McGill University, Montreal, QC H3A 2B4, Canada.ORCID 0000-0002-7975-6489
Thomas M DurcanThe Neuro's Early Drug Discovery Unit (EDDU), McGill University, Montreal, QC H3A 2B4, Canada.ORCID 0000-0003-3942-1956

Funding

The role of a-synuclein accumulation in lysosomal hydrolase trafficking and functionR01NS092823 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Joseph R Mazzulli · 2015 to 2026
$4.8M
Synergistic Enhancement of ER proteostasis, trafficking, and lysosomes as treatments for Dementia with Lewy bodies and Parkinson’s disease-dementiaR61NS138063 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI MAZZULLI, JOSEPH R · 2024 to 2024
$1.7M
NINDS NIH HHS R01 NS092823NINDS NIH HHS R61 NS138063
6 · The paper itself

Abstract

backgroundAll the processes leading to neurodegeneration cannot be addressed with just one medication. Combinations of drugs affecting various disease mechanisms concurrently could demonstrate improved effect in slowing the course of Parkinson's disease (PD).

objectiveThis was a drug-repurposing experiment designed to assess several combinations of nine drugs for possible added or synergistic efficacy using in vitro models of PD.

methodsWe evaluated 44 combinations of the nine medications (sodium phenylbutyrate, terazosin, exenatide, ambroxol, deferiprone, coenzyme-Q10, creatine, dasatinib and tauroursodeoxycholic acid) selected for their previously demonstrated evidence of their impact on different targets, showing neuroprotective properties in preclinical models of PD. We utilized wild-type induced pluripotent stem-cell-derived human dopaminergic neurons treated with 1-methyl-4-phenylpyridinium for initial screening. We retested some combinations using an idiopathic PD patient-derived induced pluripotent stem cell line and alpha-synuclein triplication line. We assessed anti-neuroinflammatory effects using human microglia cells. As metrics, we evaluated neurite length, number of branch points per mm

resultsWe have identified four combinations of two to three drugs that showed an additive protective effect in some endpoints. Only the combination of sodium phenylbutyrate, exenatide and tauroursodeoxycholic acid showed improvement in four endpoints studied.

conclusionsWe demonstrated that some of the medications, used in combination, can exert an additive neuroprotective effect in preclinical models of PD that is superior to that of each of the compounds individually. This project can lead to the development of the first treatment for PD that can slow or prevent its progression.

Indexed as

anti-inflammatory effectscombination therapydrug repurposingexenatidein vitro modelsiPSCsParkinson’s diseaseROSsodium phenylbutyratetauroursodeoxycholic acid

Identifiers

PMID40298667
PMCPMC12024093

What Socratic holds

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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 Socratic graph.