Evidence map›Paper›PMID 40175578›Full record

Trial reportJournal of neurology2025

Investigating the safety and efficacy of deoxycytidine/deoxythymidine in mitochondrial DNA depletion disorders: phase 2 open-label trial.

Saoussen Berrahmoune, Christelle Dassi, Heather Pekeles, Anthony C T Cheung, Tommy Gagnon, Paula J Waters, Daniela Buhas, Kenneth A Myers

Abstract readClinical Trial, Phase II
PubMed Publisher
In one paragraph

Trial report in Journal of neurology, 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. Use of nucleoside therapy for mitochondrial DNA depletion/deletion syndrome (MDDS).Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  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

8 authors.

Saoussen BerrahmouneResearch Institute of the McGill University Health Centre, 2155 Guy Street, Suite 500, Montreal, QC, H3H 2R9, Canada.
Christelle DassiResearch Institute of the McGill University Health Centre, 2155 Guy Street, Suite 500, Montreal, QC, H3H 2R9, Canada.
Heather PekelesDivision of Neurology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, 1001 Décarie Boulevard, Montreal, QC, H4A 3J1, Canada.
Anthony C T CheungDivision of Medical Genetics, Department of Specialized Medicine, McGill University Health Centre, 1001 Décarie Boulevard, Montreal, QC, H4A 3J1, Canada.
Tommy GagnonMedical Genetics Service, Department of Laboratory Medicine, CHUS and Department of Pediatrics, Université de Sherbrooke, Sherbrooke, QC, J1K 2R1, Canada.
Paula J WatersMedical Genetics Service, Department of Laboratory Medicine, CHUS and Department of Pediatrics, Université de Sherbrooke, Sherbrooke, QC, J1K 2R1, Canada.
Daniela BuhasDivision of Medical Genetics, Department of Specialized Medicine, McGill University Health Centre, 1001 Décarie Boulevard, Montreal, QC, H4A 3J1, Canada.
Kenneth A MyersResearch Institute of the McGill University Health Centre, 2155 Guy Street, Suite 500, Montreal, QC, H3H 2R9, Canada. kenneth.myers@mcgill.ca.ORCID http://orcid.org/0000-0001-7831-4593

Funding

Fonds de Recherche du Québec - Santé 282228Fonds de Recherche du Québec - Santé 295639
6 · The paper itself

Abstract

objectiveMitochondrial DNA depletion disorders are rare genetic disorders involving mitochondrial dysfunction. These diseases are genetically and clinically heterogeneous but share the common feature of progressively degenerative courses. At present, there are no approved treatments for mitochondrial DNA depletion disorders, though recent reports have suggested that treatment with deoxycytidine/deoxythymidine could be effective for subtypes caused by pathogenic variants in two specific genes, POLG and TK2. We investigated the therapeutic potential of deoxycytidine/deoxythymidine for people with mitochondrial DNA depletion disorders due to pathogenic variants in genes other than POLG and TK2.

methodsWe analyzed interim data from an open-label clinical trial of deoxycytidine/deoxythymidine for treatment of mitochondrial DNA depletion disorders, specifically examining disorders due to pathogenic variants in genes other than POLG and TK2. Outcome measures included Newcastle Mitochondrial Disease Scale score and serum growth differentiation factor 15, a mitochondrial function biomarker.

resultsData were available from eight individuals having pathogenic variants in FBXL4, SUCLG1, SUCLA2, or RRM2B. Newcastle Mitochondrial Disease Scale score improved in all individuals except for one who withdrew before the first follow-up visit; group level analysis was significant at 1-month and 6-month timepoints. Five patients had elevated growth differentiation factor 15 at baseline; of these, levels improved in four, including three whose values normalized.

conclusionThese data suggest deoxycytidine/deoxythymidine is a safe and therapeutically promising intervention for a broad range of mitochondrial DNA depletion disorders.

Indexed as

DeoxycytidineDNA, MitochondrialMitochondrial DiseasesThymidineAdolescentAdultChildDNA Polymerase gammaFemaleHumansMaleMiddle AgedTreatment OutcomeYoung AdultDeoxycytidineDNA, MitochondrialDNA Polymerase gammaPOLG protein, humanThymidineDeoxycytidineDeoxynucleosideDeoxythymidineFBXL4PyrimidineSUCLG1

Identifiers

PMID40175578

What OpenQuestion holds

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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.